21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2011 CFR

2011-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

21 CFR 520.1780 - Pimobendan.

Code of Federal Regulations, 2014 CFR

2014-04-01

... severe (modified New York Heart Association Class II, III, or IV) congestive heart failure due to... heart failure as appropriate on a case-by-case basis. (3) Limitations. Federal law restricts this drug...

Mixed isotype class II antigen expression. A novel class II molecule is expressed on a murine B cell lymphoma

PubMed Central

1989-01-01

The structures of Ia molecules expressed by two BALB/c B cell lymphoma lines, A20-1.11 (A20) and 2PK3, were analyzed in an effort to explain the differences in antigen-presenting capacity displayed by these cells. Alloreactive T cell hybridomas specific for I-Ad and antigen- specific, I-Ad-restricted T cells responded well to A20 as the APC. The same alloreactive T cell hybridomas responded weakly or not at all to 2PK3 and the responses of the antigen-specific, I-Ad-restricted T cells were consistently lower to antigen presented by 2PK3 as compared with A20. T cells restricted to I-Ed responded equally well to either A20 or 2PK3 as APC. Additionally 2PK3, but not A20, stimulated a strong syngeneic mixed lymphocyte response. Structural analyses of the Ia antigens revealed that I-A and I-E molecules were expressed by A20, whereas an I-E and a novel I-A-like molecule were expressed by 2PK3. The novel class II molecule was affinity purified from 2PK3 cells using an mAb specific for Ad beta (MK-D6), and this molecule was subsequently shown by an RIA to react with an E alpha-specific mAb (14-4-4S) as well. Chain-specific polyclonal antisera raised against I-A and I-E alpha and beta chains indicated that the 2PK3 "I-A" alpha chain reacted in immunoblot with E alpha-specific and not A alpha-specific antisera, whereas the beta chain reacted with A beta- and not E beta-specific antisera. Peptide map and partial amino acid sequence analyses indicated that the "I-A" molecule expressed by 2PK3 represented a mixed isotype structure resulting from the pairing of Ed alpha with Ad beta. By immunofluorescence staining analysis, 2PK3 did not react with an mAb specific for Ad alpha. 2PK3 was capable of limited antigen presentation through the mixed isotype molecule to I-Ad-restricted OVA-specific T cell hybridomas, although the responses induced were low compared with presentation through I-A on A20. Previous descriptions of the expression of mixed isotype class II molecules in the mouse have resulted primarily from DNA-mediated gene transfer experiments. The results presented indicate that a mixed isotype class II molecule can be expressed naturally. PMID:2647893

Functional Macroautophagy Induction by Influenza A Virus without a Contribution to Major Histocompatibility Complex Class II-Restricted Presentation▿†

PubMed Central

Comber, Joseph D.; Robinson, Tara M.; Siciliano, Nicholas A.; Snook, Adam E.; Eisenlohr, Laurence C.

2011-01-01

Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4+ T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4+ T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4+ response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen. PMID:21525345

In silico analysis and in vitro evaluation of immunogenic and immunomodulatory properties of promiscuous peptides derived from Leishmania infantum eukaryotic initiation factor.

PubMed

Koutsoni, Olga S; Routsias, John G; Kyriazis, Ioannis D; Barhoumi, Mourad; Guizani, Ikram; Tsakris, Athanassios; Dotsika, Eleni

2017-11-01

It is generally considered as imperative the ability to control leishmaniasis through the development of a protective vaccine capable of inducing long-lasting and protective cell-mediated immune responses. In this current study, we demonstrated potential epitopes that bind to H2 MHC class I and II molecules by conducting the in silico analysis of Leishmania infantum eukaryotic Initiation Factor (LieIF) protein, using online available algorithms. Moreover, we synthesized five peptides (16-18 amino acids long) which are part of the N-terminal portion of LieIF and contain promising MHC class I and II-restricted epitopes and afterwards, their predicted immunogenicity was evaluated in vitro by monitoring peptide-specific T-cell responses. Additionally, the immunomodulatory properties of these peptides were investigated in vitro by exploring their potential of inducing phenotypic maturation and functional differentiation of murine Bone-Marrow derived Dendritic Cells (BM-DCs). It was revealed by our data that all the synthetic peptides predicted for H2 alleles; present the property of immunogenicity. Among the synthetic peptides which contained T-cell epitopes, the peptide 52-68 aa (LieIF_2) exhibited immunomodulatory properties with the larger potential. LieIF_2-pulsed BM-DCs up-regulated the expression of the co-stimulatory surface molecules CD80 and CD86, as well as the production of the proinflammatory cytokine TNF-α and of the Th1-polarizing cytokines IL-12 and IFN-γ. The aforementioned data suggest that selected parts of LieIF could be used to develop innovative subunit protective vaccines able to induce effective immunity mediated by MHC class I-restricted as well as class II-restricted T-cell responses. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

HLA-G and MHC Class II Protein Expression in Diffuse Large B-Cell Lymphoma.

PubMed

Jesionek-Kupnicka, Dorota; Bojo, Marcin; Prochorec-Sobieszek, Monika; Szumera-Ciećkiewicz, Anna; Jabłońska, Joanna; Kalinka-Warzocha, Ewa; Kordek, Radzisław; Młynarski, Wojciech; Robak, Tadeusz; Warzocha, Krzysztof; Lech-Maranda, Ewa

2016-06-01

The expression of human leukocyte antigen-G (HLA-G) and HLA class II protein was studied by immunohistochemical staining of lymph nodes from 148 patients with diffuse large B-cell lymphoma (DLBCL) and related to the clinical course of the disease. Negative HLA-G expression was associated with a lower probability of achieving a complete remission (p = 0.04). Patients with negative HLA-G expression tended towards a lower 3-year overall survival (OS) rate compared to those with positive expression of HLA-G (p = 0.08). When restricting the analysis to patients receiving chemotherapy with rituximab, the estimated 3-year OS rate of patients with positive HLA-G expression was 73.3 % compared with 47.5 % (p = 0.03) in those with negative expression. Patients with negative HLA class II expression presented a lower 3-year OS rate compared to subjects with positive expression (p = 0.04). The loss of HLA class II expression (p = 0.05) and belonging to the intermediate high/high IPI risk group (p = 0.001) independently increased the risk of death. HLA class II expression also retained its prognostic value in patients receiving rituximab; the 3-year OS rate was 65.3 % in patients with positive HLA class II expression versus 29.6 % (p = 0.04) in subjects that had loss of HLA class II expression. To our knowledge, for the first time, the expression of HLA-G protein in DLBCL and its association with the clinical course of the disease was demonstrated. Moreover, the link between losing HLA class II protein expression and poor survival of patients treated with immunochemotherapy was confirmed.

Psychological Factors Associated with Weight Loss in Obese and Severely Obese Women in a Behavioral Physical Activity Intervention

ERIC Educational Resources Information Center

Annesi, James J.; Whitaker, Ann C.

2010-01-01

The behavioral processes of weight reduction are poorly understood, and responses to treatments based primarily on caloric restriction have been unfavorable. A theory-based path derived from proposed relations of physical activity, changes in psychological factors, and weight loss was separately tested with women with Class I and Class II obesity…

Modeling alternative binding registers of a minimal immunogenic peptide on two class II major histocompatibility complex (MHC II) molecules predicts polarized T-cell receptor (TCR) contact positions.

PubMed

Murray, J S; Fois, S D S; Schountz, T; Ford, S R; Tawde, M D; Brown, J C; Siahaan, T J

2002-03-01

Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.

An analysis of variation in the long-range genomic organization of the human major histocompatibility complex class II region by pulsed-field gel electrophoresis.

PubMed

Dunham, I; Sargent, C A; Dawkins, R L; Campbell, R D

1989-11-01

The class II region of the human major histocompatibility complex in seven common HLA haplotypes has been analyzed using pulsed-field gel electrophoresis, restriction enzymes that cut genomic DNA infrequently, and Southern blotting. This analysis has revealed that there are differences in the amount of DNA present in the DQ and DR subregions dependent on the haplotype. The class II region of the DR3 haplotype spans approximately 750 kb and has the same amount of DNA as the class II region of the DR5 and DR6 haplotypes. However, the DR2 haplotype has approximately 30 kb more DNA within the DR subregion. The DR4 haplotype has an additional approximately 110 kb of DNA within the DQ or DR subregions compared to the DR3, DR5, and DR6 haplotypes. These haplotype-specific differences could have some bearing both on the analysis of disease susceptibility and on the ability of chromosomes possessing different HLA haplotypes to recombine within the DQ/DR subregions.

Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

PubMed Central

Dzuris, John L.; Sidney, John; Horton, Helen; Correa, Rose; Carter, Donald; Chesnut, Robert W.; Watkins, David I.; Sette, Alessandro

2001-01-01

Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307–319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV. PMID:11602736

Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53.

PubMed

Rojas, José Manuel; McArdle, Stephanie E B; Horton, Roger B V; Bell, Matthew; Mian, Shahid; Li, Geng; Ali, Selman A; Rees, Robert C

2005-03-01

Because of the central role of CD4(+) T cells in antitumour immunity, the identification of the MHC class II-restricted peptides to which CD4(+) T cells respond has become a priority of tumour immunologists. Here, we describe a strategy permitting us to rapidly determine the immunogenicity of candidate HLA-DR-restricted peptides using peptide immunisation of HLA-DR-transgenic mice, followed by assessment of the response in vitro. This strategy was successfully applied to the reported haemaglutinin influenza peptide HA(307-319), and then extended to three candidate HLA-DR-restricted p53 peptides predicted by the evidence-based algorithm SYFPEITHI to bind to HLA-DRbeta1*0101 (HLA-DR1) and HLA-DRbeta1*0401 (HLA-DR4) molecules. One of these peptides, p53(108-122), consistently induced responses in HLA-DR1- and in HLA-DR4-transgenic mice. Moreover, this peptide was naturally processed by dendritic cells (DCs), and induced specific proliferation in the splenocytes of mice immunised with p53 cDNA, demonstrating that immune responses could be naturally mounted to the peptide. Furthermore, p53(108-122) peptide was also immunogenic in HLA-DR1 and HLA-DR4 healthy donors. Thus, the use of this transgenic model permitted the identification of a novel HLA-DR-restricted epitope from p53 and constitutes an attractive approach for the rapid identification of novel immunogenic MHC class II-restricted peptides from tumour antigens, which can ultimately be incorporated in immunotherapeutic protocols.

Characterization of class II alpha genes and DLA-D region allelic associations in the dog.

PubMed

Sarmiento, U M; Storb, R F

1988-10-01

Human major histocompatibility complex (HLA) cDNA probes were used to analyze the restriction fragment length polymorphism (RFLP) of the alpha genes of the DLA-D region in dogs. Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA-D homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (BamHI, EcoRI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I and Bgl II), separated by agarose gel electrophoresis and transferred onto Biotrace membrane. The Southern blots were successively hybridized with radiolabelled HLA cDNA probes corresponding to DQ, DP, DZ and DR alpha genes. Clear evidence was obtained for the canine homologues of DQ and DR alpha genes with simple bi- or tri-allelic polymorphism respectively. Evidence for a single, nonpolymorphic DP alpha gene was also obtained. However, the presence of a DZ alpha gene could not be clearly demonstrated in canine genomic DNA. This report extends our previous RFLP analysis documenting polymorphism of DLA class II beta genes in the same panel of homozygous typing cell dogs, and provides the basis for DLA-D genotyping at a population level. This study also characterizes the RFLP-defined preferential allelic associations across the DLA-D region in nine different homozygous typing cell specificities.

Toward a Network Model of MHC Class II-Restricted Antigen Processing

PubMed Central

Miller, Michael A.; Ganesan, Asha Purnima V.; Eisenlohr, Laurence C.

2013-01-01

The standard model of Major Histocompatibility Complex class II (MHCII)-restricted antigen processing depicts a straightforward, linear pathway: internalized antigens are converted into peptides that load in a chaperone dependent manner onto nascent MHCII in the late endosome, the complexes subsequently trafficking to the cell surface for recognition by CD4+ T cells (TCD4+). Several variations on this theme, both moderate and radical, have come to light but these alternatives have remained peripheral, the conventional pathway generally presumed to be the primary driver of TCD4+ responses. Here we continue to press for the conceptual repositioning of these alternatives toward the center while proposing that MHCII processing be thought of less in terms of discrete pathways and more in terms of a network whose major and minor conduits are variable depending upon many factors, including the epitope, the nature of the antigen, the source of the antigen, and the identity of the antigen-presenting cell. PMID:24379819

[Inequalities in health according to social class in Catalonia, 1994].

PubMed

Fernández, E; Schiaffino, A; Rajmil, L; Borrell, C; García, M; Segura, A

2000-05-15

To study social inequalities in health in Catalonia. Cross-sectional survey of a representative sample of the population of Catalonia, Spain (Catalan Health Interview Survey, 1994). Responses from 5641 males and 6604 women aged 15 years or over were included for analysis. We analysed the information about self-perceived health, restriction of activity, and presence of chronic conditions according to social class by means of logistic regression models. The proportion of subjects that rated their health as fair or poor was higher in social classes IV-V than in classes I-II (men: 25.0% vs. 14.5%; OR, 1.8, 95% CI, 1.5-2.3; women: 34.4% vs. 21.5%; OR, 1.7, 95% CI, 1.4-2.1). There were differences by social class in respect to restriction of activity and presence of chronic conditions. Despite the decrease of social inequalities in accesibility and use of health services due to the universalisation of health coverage, differences by social class remain in the perception of health status. These inequalities should be addressed by the health system within the framework of broad public and social policies.

The major histocompatibility complex of tassel-eared squirrels. II. Genetic diversity associated with Abert squirrels.

PubMed

Wettstein, P J; States, J S

1986-01-01

The extent of polymorphism and the rate of divergence of class I and class II sequences mapping to the mammalian major histocompatibility complex (MHC) have been the subject of experimentation and speculation. To provide further insight into the evolution of the MHC we have initiated the analysis of two geographically isolated subspecies of tassel-eared squirrels. In the preceding communication we described the number and polymorphism of TSLA class I and class II sequences in Kaibab squirrels (S. aberti kaibabensis), which live north of the Grand Canyon. In this report we present a parallel analysis of Abert squirrels (S. aberti aberti), which live south of the Grand Canyon in northern Arizona. Genomic DNA from 12 Abert squirrels was digested with restriction enzymes, electrophoresed, blotted, and hybridized with DR alpha, DR beta, DQ alpha, DQ beta, and HLA-B7 probes. The results of these hybridizations were remarkably similar to those obtained in Kaibab squirrels. The majority of class I and class II bands were identical in size and number, suggesting that Abert and Kaibab squirrels have not significantly diverged in the TSLA complex despite their geographical separation. Relative polymorphism of class II sequences was similar to that observed with Kaibab squirrels: beta sequences exhibited higher polymorphism than alpha sequences. As in Kaibab squirrels, a number of alpha and beta sequences were apparently carried on the same fragments. In comparison to class II beta sequences, there was limited polymorphism in class I sequences, although a diverse number of class I genotypes were observed. Attempts to identify segregating TSLA haplotypes were futile in that the only families of sequences with concordant distributions were DQ alpha and DQ beta. These observations and those obtained with Kaibab squirrels suggest that the present-day TSLA haplotypes of both subspecies are derived from a limited number of common, progenitor haplotypes through repeated intra-TSLA recombination.

Treatment and posttreatment effects induced by the Forsus appliance: A controlled clinical study.

PubMed

Cacciatore, Giorgio; Ghislanzoni, Luis Tomas Huanca; Alvetro, Lisa; Giuntini, Veronica; Franchi, Lorenzo

2014-11-01

To evaluate treatment and posttreatment dentoskeletal effects induced by the Forsus device (FRD) in growing patients with Class II malocclusion in a retrospective controlled clinical study. Thirty-six Class II patients (mean [SD] age 12.3 [1.2] years) were treated consecutively with the FRD protocol and compared with a sample of 20 subjects with untreated Class II malocclusion (mean [SD] age 12.2 [0.9] years). Lateral cephalograms were taken at the beginning of treatment, at the end of comprehensive treatment (after 2.3 ± 0.4 years), and at a postretention period (after 2.3 ± 1.1 years from the end of comprehensive treatment). Statistical comparisons were carried out with the unpaired t-test and Benjamini-Hochberg correction (P < .05). After comprehensive treatment, the FRD sample showed a significant restriction of the sagittal maxillary growth together with a significant correction in overjet, overbite, and molar relationship. During the overall observation interval, the FRD group exhibited no significant sagittal or vertical skeletal changes, while significant improvements were recorded in overjet (-3.8 mm), overbite (-1.5 mm), and molar relationship (+3.7 mm). The FRD protocol was effective in correcting Class II malocclusion mainly at the dentoalveolar level when evaluated 2 years after the end of comprehensive treatment.

Processing of two latent membrane protein 1 MHC class I epitopes requires tripeptidyl peptidase II involvement.

PubMed

Diekmann, Jan; Adamopoulou, Eleni; Beck, Olaf; Rauser, Georg; Lurati, Sarah; Tenzer, Stefan; Einsele, Hermann; Rammensee, Hans-Georg; Schild, Hansjörg; Topp, Max S

2009-08-01

The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential target for T cell immunotherapy in EBV-related malignancies. However, only a few CD8(+) T cell epitopes are known, and the benefit of LMP1-specific T cell immunotherapy has not yet been proven. In this work, we studied the processing of the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL. We found that target cells endogenously expressing the native LMP1 are not recognized by CTLs specific for these epitopes because the N-terminal part of LMP1 limits the efficiency of epitope generation. We further observed that the proteasome is not required for the generation of both epitopes and that the YLLEMLRWL epitope seems to be destroyed by the proteasome, because blocking of proteasomal activities enhanced specific CTL activation. Activation of LMP1-specific CTLs could be significantly reduced after inhibition of the tripeptidyl peptidase II, suggesting a role for this peptidase in the processing of both epitopes. Taken together, our results demonstrate that the MHC class I-restricted LMP1 epitopes studied in this work are two of very few epitopes known to date to be processed proteasome independently by tripeptidyl peptidase II.

Structural basis of human β-cell killing by CD8+ T cells in Type 1 diabetes

PubMed Central

Bulek, Anna M.; Cole, David K.; Skowera, Ania; Dolton, Garry; Gras, Stephanie; Madura, Florian; Fuller, Anna; Miles, John J.; Gostick, Emma; Price, David A.; Drijfhout, Jan W.; Knight, Robin R.; Huang, Guo C.; Lissin, Nikolai; Molloy, Peter E.; Wooldridge, Linda; Jakobsen, Bent K.; Rossjohn, Jamie; Peakman, Mark; Rizkallah, Pierre J.; Sewell, Andrew K.

2011-01-01

The structural characteristics of autoreactive-T cell receptor (TCR) engagement of major histocompatability (MHC) class II-restricted self-antigens is established, but how autoimmune-TCRs interact with self-MHC class I has been unclear. We examined how CD8+ T cells kill human islet β-cells, in Type-1 diabetes, via autoreactive-TCR (1E6) recognition of an HLA-A*0201-restricted glucose-sensitive preproinsulin peptide. Rigid ‘lock-and-key’ binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHCI-restricted TCRs. However, this interaction was extraordinarily weak, due to limited contacts with MHCI. TCR binding was highly peptide-centric, dominated by two CDR3-loop-encoded residues, acting as an ‘aromatic-cap’, over the peptide MHCI (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8+ T cell-mediated autoreactivity. PMID:22245737

Comparison of the effects of fixed and removable functional appliances on the skeletal and dentoalveolar structures.

PubMed

Bilgiç, Fundagül; Hamamci, Orhan; Başaran, Güvenç

2011-11-01

To compare and analyse the effects of activator and Forsus FRD EZ appliances in the treatment of skeletal Class II division I malocclusion. Lateral cephalograms and hand-wrist radiographs were collected from 24 Class II division I growing patients (14 females, 10 males). The patients were randomly divided into two equal groups and either treated with an activator appliance (Mean age 12.67 +/- 1.24 years) or with a Forsus FRD EZ appliance (Mean age 12.31 +/- 1.09 years). Pretreatment and posttreatment cephalometric radiographs were obtained, traced, superimposed and data analysed using paired t-tests and the Wilcoxon signed rank test. The results demonstrated that the Forsus FRD EZ effectively corrected the Class II malocclusion, but the changes were mainly dentoalveolar. The Forsus FRD EZ appliance induced a clockwise rotation of the occlusal plane without significant alteration in the vertical facial dimension. Skeletally, maxillary growth was restricted and pogonion moved forward which improved the profile. The Forsus FRD EZ appliance may be an effective dentoalveolar treatment method to manage a skeletal imbalance and improve the profile in growing patients.

BiodMHC: an online server for the prediction of MHC class II-peptide binding affinity.

PubMed

Wang, Lian; Pan, Danling; Hu, Xihao; Xiao, Jinyu; Gao, Yangyang; Zhang, Huifang; Zhang, Yan; Liu, Juan; Zhu, Shanfeng

2009-05-01

Effective identification of major histocompatibility complex (MHC) molecules restricted peptides is a critical step in discovering immune epitopes. Although many online servers have been built to predict class II MHC-peptide binding affinity, they have been trained on different datasets, and thus fail in providing a unified comparison of various methods. In this paper, we present our implementation of seven popular predictive methods, namely SMM-align, ARB, SVR-pairwise, Gibbs sampler, ProPred, LP-top2, and MHCPred, on a single web server named BiodMHC (http://biod.whu.edu.cn/BiodMHC/index.html, the software is available upon request). Using a standard measure of AUC (Area Under the receiver operating characteristic Curves), we compare these methods by means of not only cross validation but also prediction on independent test datasets. We find that SMM-align, ProPred, SVR-pairwise, ARB, and Gibbs sampler are the five best-performing methods. For the binding affinity prediction of class II MHC-peptide, BiodMHC provides a convenient online platform for researchers to obtain binding information simultaneously using various methods.

Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells.

PubMed

Tsuji, Takemasa; Matsuzaki, Junko; Caballero, Otavia L; Jungbluth, Achim A; Ritter, Gerd; Odunsi, Kunle; Old, Lloyd J; Gnjatic, Sacha

2012-04-15

Tumor Ag-specific CD4(+) T cells play important functions in tumor immunosurveillance, and in certain cases they can directly recognize HLA class II-expressing tumor cells. However, the underlying mechanism of intracellular Ag presentation to CD4(+) T cells by tumor cells has not yet been well characterized. We analyzed two naturally occurring human CD4(+) T cell lines specific for different peptides from cytosolic tumor Ag NY-ESO-1. Whereas both lines had the same HLA restriction and a similar ability to recognize exogenous NY-ESO-1 protein, only one CD4(+) T cell line recognized NY-ESO-1(+) HLA class II-expressing melanoma cells. Modulation of Ag processing in melanoma cells using specific molecular inhibitors and small interfering RNA revealed a previously undescribed peptide-selective Ag-presentation pathway by HLA class II(+) melanoma cells. The presentation required both proteasome and endosomal protease-dependent processing mechanisms, as well as cytosolic heat shock protein 90-mediated chaperoning. Such tumor-specific pathway of endogenous HLA class II Ag presentation is expected to play an important role in immunosurveillance or immunosuppression mediated by various subsets of CD4(+) T cells at the tumor local site. Furthermore, targeted activation of tumor-recognizing CD4(+) T cells by vaccination or adoptive transfer could be a suitable strategy for enhancing the efficacy of tumor immunotherapy.

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model

PubMed Central

Mukherjee, P.; Pathangey, L.B.; Bradley, J.B.; Tinder, T.L.; Basu, G.D.; Akporiaye, E.T.; Gendler, S.J.

2007-01-01

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan helper peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-γ-producing CD4+ helper and CD8+ cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced. PMID:17166639

MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

PubMed

Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

2007-02-19

A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

Restricted movement by mottled sculpin (Pisces: Cottidae) in a southern Appalachian stream.

Treesearch

J. Todd Petty; Gary D. Grossman

2004-01-01

1. We used direct observation and mark-recapture techniques to quantify movements by mottled sculpins (Cottus bairdi) in a 1 km segment of Shope Fork in western North Carolina. Our objectives were to: (i) quantify the overall rate of sculpin movement, (ii) assess variation in movement among years, individuals, and sculpin size classes, (iii) relate movement to...

40 CFR 1048.615 - What are the provisions for exempting engines designed for lawn and garden applications?

Code of Federal Regulations, 2010 CFR

2010-07-01

... certificate of conformity showing that it meets emission standards for Class II engines under 40 CFR part 90... requirements and restrictions of 40 CFR part 90 or 1054 apply to anyone manufacturing these engines, anyone manufacturing equipment that uses these engines, and all other persons in the same manner as if these engines...

Identification of a CD8 T cell that can independently mediate autoimmune diabetes development in the complete absence of CD4 T cell helper functions.

PubMed

Graser, R T; DiLorenzo, T P; Wang, F; Christianson, G J; Chapman, H D; Roopenian, D C; Nathenson, S G; Serreze, D V

2000-04-01

Previous work has indicated that an important component for the initiation of autoimmune insulin-dependent diabetes mellitus (IDDM) in the NOD mouse model entails MHC class I-restricted CD8 T cell responses against pancreatic beta cell Ags. However, unless previously activated in vitro, such CD8 T cells have previously been thought to require helper functions provided by MHC class II-restricted CD4 T cells to exert their full diabetogenic effects. In this study, we show that IDDM development is greatly accelerated in a stock of NOD mice expressing TCR transgenes derived from a MHC class I-restricted CD8 T cell clone (designated AI4) previously found to contribute to the earliest preclinical stages of pancreatic beta cell destruction. Importantly, these TCR transgenic NOD mice (designated NOD.AI4alphabeta Tg) continued to develop IDDM at a greatly accelerated rate when residual CD4 helper T cells were eliminated by introduction of the scid mutation or a functionally inactivated CD4 allele. In a previously described stock of NOD mice expressing TCR transgenes derived from another MHC class I-restricted beta cell autoreactive T cell clone, IDDM development was retarded by elimination of residual CD4 T cells. Hence, there is variability in the helper dependence of CD8 T cells contributing to the development of autoimmune IDDM. The AI4 clonotype represents the first CD8 T cell with a demonstrated ability to progress from a naive to functionally activated state and rapidly mediate autoimmune IDDM development in the complete absence of CD4 T cell helper functions.

Performance of exhaust-protective (class I) biological 'safety' cabinets.

PubMed Central

Newsom, S W

1979-01-01

Nineteen open-fronted (class I) safety cabinets were subjected to spore containment and airflow tests, which suggested that a flow of 0.75 m/s was the minimum required for safe operation; further tests on three of the cabinets were repeated at different air speeds and confirmed this. The airflow is required to overcome the effect of laboratory or external air currents. Contamination of surfaces (including the operator's hands) by aerosols liberated inside the cabinets was investigated and found to depend more on turbulence within the cabinet (as from a restricted front opening) than on the number of air changes. The findings suggest that the product protection provided by a well-designed class I cabinet might equal that of a class II (laminar flow) unit. Images Fig. 6 PMID:469014

A novel Minimalist Cell-Free MHC Class II Antigen Processing System Identifies Immunodominant Epitopes

PubMed Central

Hartman, Isamu Z.; Kim, AeRyon; Cotter, Robert J.; Walter, Kimberly; Dalai, Sarat K.; Boronina, Tatiana; Griffith, Wendell; Schwenk, Robert; Lanar, David E.; Krzych, Urszula; Cole, Robert N.; Sadegh-Nasseri, Scheherazade

2010-01-01

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4+ T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: MHC class II, cathepsins, and HLA-DM. Our minimalist system successfully identified the physiologically selected immunodominant epitopes of model antigens, HA1 from influenza virus (A/Texas/1/77) and type II collagen. When applied for de novo epitope identification to a malaria antigen, or HA1 from H5N1 virus (Avian Flu), the system selected a single epitope from each protein that were confirmed to be immunodominant by their capacity to activate CD4+ T cells in HLA-DR1 positive human volunteers or transgenic mice immunized with the corresponding proteins. Thus, we provide a powerful new tool for the identification of physiologically relevant helper T cell epitopes from antigens. PMID:21037588

Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD

PubMed Central

Leveque-El mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A.; Cheong, Melody; Kuns, Rachel D.; Lineburg, Katie E.; Teal, Bianca E.; Alexander, Kylie A.; Clouston, Andrew D.; Blazar, Bruce R.; Hill, Geoffrey R.

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. PMID:27338097

Corruption of dendritic cell antigen presentation during acute GVHD leads to regulatory T-cell failure and chronic GVHD.

PubMed

Leveque-El Mouttie, Lucie; Koyama, Motoko; Le Texier, Laetitia; Markey, Kate A; Cheong, Melody; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Alexander, Kylie A; Clouston, Andrew D; Blazar, Bruce R; Hill, Geoffrey R; MacDonald, Kelli P A

2016-08-11

Chronic graft-versus-host disease (cGVHD) is a major cause of late mortality following allogeneic bone marrow transplantation (BMT) and is characterized by tissue fibrosis manifesting as scleroderma and bronchiolitis obliterans. The development of acute GVHD (aGVHD) is a powerful clinical predictor of subsequent cGVHD, suggesting that aGVHD may invoke the immunologic pathways responsible for cGVHD. In preclinical models in which sclerodermatous cGVHD develops after a preceding period of mild aGVHD, we show that antigen presentation within major histocompatibility complex (MHC) class II of donor dendritic cells (DCs) is markedly impaired early after BMT. This is associated with a failure of regulatory T-cell (Treg) homeostasis and cGVHD. Donor DC-restricted deletion of MHC class II phenocopied this Treg deficiency and cGVHD. Moreover, specific depletion of donor Tregs after BMT also induced cGVHD, whereas adoptive transfer of Tregs ameliorated it. These data demonstrate that the defect in Treg homeostasis seen in cGVHD is a causative lesion and is downstream of defective antigen presentation within MHC class II that is induced by aGVHD. © 2016 by The American Society of Hematology.

CD4+ T cell-mediated rejection of MHC class II-positive tumor cells is dependent on antigen secretion and indirect presentation on host APCs.

PubMed

Haabeth, Ole Audun Werner; Fauskanger, Marte; Manzke, Melanie; Lundin, Katrin U; Corthay, Alexandre; Bogen, Bjarne; Tveita, Anders Aune

2018-05-11

Tumor-specific CD4+ T cells have been shown to mediate efficient anti-tumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4+ T cell-driven anti-tumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4+ T cells in vivo. These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4+ T cell-mediated rejection, and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4+ T cells. Copyright ©2018, American Association for Cancer Research.

Discrimination Between Human Leukocyte Antigen Class I-Bound and Co-Purified HIV-Derived Peptides in Immunopeptidomics Workflows

PubMed Central

Partridge, Thomas; Nicastri, Annalisa; Kliszczak, Anna E.; Yindom, Louis-Marie; Kessler, Benedikt M.; Ternette, Nicola; Borrow, Persephone

2018-01-01

Elucidation of novel peptides presented by human leukocyte antigen (HLA) class I alleles by immunopeptidomics constitutes a powerful approach that can inform the rational design of CD8+ T cell inducing vaccines to control infection with pathogens such as human immunodeficiency virus type 1 (HIV-1) or to combat tumors. Recent advances in the sensitivity of liquid chromatography tandem mass spectrometry instrumentation have facilitated the discovery of thousands of natural HLA-restricted peptides in a single measurement. However, the extent of contamination of class I-bound peptides identified using HLA immunoprecipitation (IP)-based immunopeptidomics approaches with peptides from other sources has not previously been evaluated in depth. Here, we investigated the specificity of the IP-based immunopeptidomics methodology using HLA class I- or II-deficient cell lines and membrane protein-specific antibody IPs. We demonstrate that the 721.221 B lymphoblastoid cell line, widely regarded to be HLA class Ia-deficient, actually expresses and presents peptides on HLA-C*01:02. Using this cell line and the C8166 (HLA class I- and II-expressing) cell line, we show that some HLA class II-bound peptides were co-purified non-specifically during HLA class I and membrane protein IPs. Furthermore, IPs of “irrelevant” membrane proteins from HIV-1-infected HLA class I- and/or II-expressing cells revealed that unusually long HIV-1-derived peptides previously reported by us and other immunopeptidomics studies as potentially novel CD8+ T cell epitopes were non-specifically co-isolated, and so constitute a source of contamination in HLA class I IPs. For example, a 16-mer (FLGKIWPSYKGRPGNF), which was detected in all samples studied represents the full p1 segment of the abundant intracellular or virion-associated proteolytically-processed HIV-1 Gag protein. This result is of importance, as these long co-purified HIV-1 Gag peptides may not elicit CD8+ T cell responses when incorporated into candidate vaccines. These results have wider implications for HLA epitope discovery from abundant or membrane-associated antigens by immunopeptidomics in the context of infectious diseases, cancer, and autoimmunity. PMID:29780384

A comparision of Twin-block and Forsus (FRD) functional appliance--a cephalometric study.

PubMed

Mahamad, Irfanulla Khan; Neela, Praveen Kumar; Mascarenhas, Rohan; Husain, Akhter

2012-01-01

The aim was to compare the effects of Twin-block & Forsus (FRD) functional appliances in the correction of Angles Class II division 1 malocclusions. Pre- and post-treatment lateral cephalograms of 25 patients who underwent treatment with twin block for the correction of class II div 1 were compared with 25 patients who underwent treatment with Forsus appliance. These were again compared with the pre follow up and post follow up lateral cephalograms of 25 patients who have not undergone any treatment during this period. All the 3 group patients were compared for skeletal, dental and soft tissue parameters. Cephalometric analysis revealed that both Twin-block & Forsus Fatigue Resistant Device (FRD) appliances stimulated mandibular growth. Statistically significant differences between the two groups were found. Twin-block patients showed statistically very high significant (p < 0.001) increase in mandibular length (6.02 mm) whereas Forsus appliance patients showed significant (p < 0.05) increase in mandibular length (1.6 mm) when compared with control group (0.3 mm). No significant restriction of maxillary growth was found in either of the two experimental groups when compared to control group. Significant increase in lower anterior facial height & posterior facial height was observed in both experimental groups in relation to control group. Significant reduction of overjet and overbite was observed in both experimental groups. Class I molar relationship and improvement in the soft tissue profile were achieved in both treatment groups compared with control group. Both Twin Block and Forsus were effective in the treatment of Class II Div 1 malocclusion. Class II correction with Twin-block is more due to mandibular skeletal and dentoalveolar changes whereas in Forsus, it is more due to dentoalveolar changes and less skeletal changes.

11 CFR 114.3 - Disbursements for communications to the restricted class in connection with a Federal election.

Code of Federal Regulations, 2011 CFR

2011-01-01

... or party representative, to address its restricted class, and permits the news media to cover or... restricted class in connection with a Federal election. 114.3 Section 114.3 Federal Elections FEDERAL... communications to the restricted class in connection with a Federal election. (a) General. (1) Corporations and...

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection.

PubMed

Li, Sam X; Barrett, Bradley S; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L

2016-02-05

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation.

Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection

PubMed Central

Li, Sam X.; Barrett, Bradley S.; Guo, Kejun; Kassiotis, George; Hasenkrug, Kim J.; Dittmer, Ulf; Gibbert, Kathrin; Santiago, Mario L.

2016-01-01

Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co-stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV-specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID:26846717

Heterogeneity of porcine alveolar macrophages in experimental pneumonia.

PubMed

Berndt, A; Müller, G

1997-07-01

The aim of the study was the morphological and the phenotypic characterization of the porcine non-lymphocytic bronchoalveolar lavage (BAL) cell population of unaffected- and intrabronchial with Pasteurella multocida- (P.m.) infected swine using flow cytometry. Three non-lymphocytic cell populations of the porcine bronchoalveolar lavage could be differentiated: (1) large, high autofluorescent cells, (LHC); (2) small, high autofluorescent cells, (SHC); (3) small, low autofluorescent cells, (SLC). In comparison with the control animals, the percentage of the LHC and SHC within the whole non-lymphocytic cell population was decreased, whereas the SLC was significantly enhanced after infection. In order to investigate the phenotype of these cell populations, monoclonal antibodies against porcine antigens (SWC1, SWC3a, MHC class II, 2G6 (against macrophages)) were used. The results showed that the cells of the SLC seem to belong to the granulocytes, whereas the LHC and the SHC are lung macrophages. After the infection of the animals the percentage of the SWC1 positive cells of LHC and SHC were significantly increased, indicating an entrance of more immature macrophages. The percentage of the MHC class II antibody binding cells of all three non-lymphocytic populations was-decreased after infection, indicating a restricted MHC class II dependent antigen recognition in P.m. pneumonia.

Activation of Nrf2 is required for up-regulation of the π class of glutathione S-transferase in rat primary hepatocytes with L-methionine starvation.

PubMed

Lin, Ai-Hsuan; Chen, Haw-Wen; Liu, Cheng-Tze; Tsai, Chia-Wen; Lii, Chong-Kuei

2012-07-04

Numerous genes expression is regulated in response to amino acid shortage, which helps organisms adapt to amino acid limitation. The expression of the π class of glutathione (GSH) S-transferase (GSTP), a highly inducible phase II detoxification enzyme, is regulated mainly by activates activating protein 1 (AP-1) binding to the enhancer I of GSTP (GPEI). Here we show the critical role of nuclear factor erythroid-2-related factor 2 (Nrf2) in up-regulating GSTP gene transcription. Primary rat hepatocytes were cultured in a methionine-restricted medium, and immunoblotting and RT-PCR analyses showed that methionine restriction time-dependently increased GSTP protein and mRNA expression over a 48 h period. Nrf2 translocation to the nucleus, nuclear proteins binding to GPEI, and antioxidant response element (ARE) luciferase reporter activity were increased by methionine restriction as well as by l-buthionine sulfoximine (BSO), a GSH synthesis inhibitor. Transfection with Nrf2 siRNA knocked down Nrf2 expression and reversed the methionine-induced GSTP expression and GPEI binding activity. Chromatin immunoprecipitation assay confirmed the binding of Nrf2 to the GPEI. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells. ERK2 siRNA abolished methionine restriction-induced Nrf2 nuclear translocation, GPEI binding activity, ARE-luciferase reporter activity, and GSTP expression. Our results suggest that the up-regulation of GSTP gene transcription in response to methionine restriction likely occurs via the ERK-Nrf2-GPEI signaling pathway.

Immunoinformatics Approach in Designing Epitope-based Vaccine Against Meningitis-inducing Bacteria (Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae Type b).

PubMed

Zahroh, Hilyatuz; Ma'rup, Ahmad; Tambunan, Usman Sumo Friend; Parikesit, Arli Aditya

2016-01-01

Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. Furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. Recently, research on epitope-based vaccines has been developed intensively. Such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the antibody. In this study, we developed epitope-based vaccine candidates against various meningitis-inducing bacteria, including Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type b. The epitopes were selected from their protein of polysaccharide capsule. B-cell epitopes were predicted by using BCPred, while T-cell epitope for major histocompatibility complex (MHC) class I was predicted using PAProC, TAPPred, and Immune Epitope Database. Immune Epitope Database was also used to predict T-cell epitope for MHC class II. Population coverage and molecular docking simulation were predicted against previously generated epitope vaccine candidates. The best candidates for MHC class I- and class II-restricted T-cell epitopes were MQYGDKTTF, MKEQNTLEI, ECTEGEPDY, DLSIVVPIY, YPMAMMWRNASNRAI, TLQMTLLGIVPNLNK, ETSLHHIPGISNYFI, and SLLYILEKNAEMEFD, which showed 80% population coverage. The complexes of class I T-cell epitopes-HLA-C*03:03 and class II T-cell epitopes-HLA-DRB1*11:01 showed better affinity than standards as evaluated from their Δ G binding value and the binding interaction between epitopes and HLA molecules. These peptide constructs may further be undergone in vitro and in vivo testings for the development of targeted vaccine against meningitis infection.

Preventing vaccinia virus class-I epitopes presentation by HSV-ICP47 enhances the immunogenicity of a TAP-independent cancer vaccine epitope.

PubMed

Raafat, Nermin; Sadowski-Cron, Charlotte; Mengus, Chantal; Heberer, Michael; Spagnoli, Giulio C; Zajac, Paul

2012-09-01

Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein. To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12). In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells. While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected. Characterization of rVV-MUS12 infected cells demonstrates that over-expression of a TAP-independent peptide, partially compensates for ICP47 induced surface MHC class-I downregulation (30% vs. 70% respectively). Most importantly, in conditions where clearance of infected APC by virus-specific CTL represents a limiting factor, a significant enhancement of CTL responses to the tumor epitope can be detected in cultures stimulated with rVV-MUS12, as compared to those stimulated by rVV-MART alone. Such reagents could become of high relevance in multiple boost protocols required for cancer immunotherapy, to limit vector-specific responsiveness. Copyright © 2011 UICC.

HLA Class I Binding 9mer Peptides from Influenza A Virus Induce CD4+ T Cell Responses

PubMed Central

Wang, Mingjun; Larsen, Mette V.; Nielsen, Morten; Harndahl, Mikkel; Justesen, Sune; Dziegiel, Morten H.; Buus, Søren; Tang, Sheila T.; Lund, Ole; Claesson, Mogens H.

2010-01-01

Background Identification of human leukocyte antigen class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes from influenza virus is of importance for the development of new effective peptide-based vaccines. Methodology/Principal Findings In the present work, bioinformatics was used to predict 9mer peptides derived from available influenza A viral proteins with binding affinity for at least one of the 12 HLA-I supertypes. The predicted peptides were then selected in a way that ensured maximal coverage of the available influenza A strains. One hundred and thirty one peptides were synthesized and their binding affinities for the HLA-I supertypes were measured in a biochemical assay. Influenza-specific T cell responses towards the peptides were quantified using IFNγ ELISPOT assays with peripheral blood mononuclear cells (PBMC) from adult healthy HLA-I typed donors as responder cells. Of the 131 peptides, 21 were found to induce T cell responses in 19 donors. In the ELISPOT assay, five peptides induced responses that could be totally blocked by the pan-specific anti-HLA-I antibody W6/32, whereas 15 peptides induced responses that could be completely blocked in the presence of the pan-specific anti-HLA class II (HLA-II) antibody IVA12. Blocking of HLA-II subtype reactivity revealed that 8 and 6 peptide responses were blocked by anti-HLA-DR and -DP antibodies, respectively. Peptide reactivity of PBMC depleted of CD4+ or CD8+ T cells prior to the ELISPOT culture revealed that effectors are either CD4+ (the majority of reactivities) or CD8+ T cells, never a mixture of these subsets. Three of the peptides, recognized by CD4+ T cells showed binding to recombinant DRA1*0101/DRB1*0401 or DRA1*0101/DRB5*0101 molecules in a recently developed biochemical assay. Conclusions/Significance HLA-I binding 9mer influenza virus-derived peptides induce in many cases CD4+ T cell responses restricted by HLA-II molecules. PMID:20479886

Immunologic hierarchy, class II MHC promiscuity, and epitope spreading of a melanoma helper peptide vaccine.

PubMed

Hu, Yinin; Petroni, Gina R; Olson, Walter C; Czarkowski, Andrea; Smolkin, Mark E; Grosh, William W; Chianese-Bullock, Kimberly A; Slingluff, Craig L

2014-08-01

Immunization with a combination melanoma helper peptide (6MHP) vaccine has been shown to induce CD4(+) T cell responses, which are associated with patient survival. In the present study, we define the relative immunogenicity and HLA allele promiscuity of individual helper peptides and identify helper peptide-mediated augmentation of specific CD8(+) T cell responses. Thirty-seven participants with stage IIIB-IV melanoma were vaccinated with 6MHP in incomplete Freund's adjuvant. The 6MHP vaccine is comprised of 6 peptides representing melanocytic differentiation proteins gp100, tyrosinase, Melan-A/MART-1, and cancer testis antigens from the MAGE family. CD4(+) and CD8(+) T cell responses were assessed in peripheral blood and in sentinel immunized nodes (SIN) by thymidine uptake after exposure to helper peptides and by direct interferon-γ ELIspot assay against 14 MHC class I-restricted peptides. Vaccine-induced CD4(+) T cell responses to individual epitopes were detected in the SIN of 63 % (22/35) and in the peripheral blood of 38 % (14/37) of participants for an overall response rate of 65 % (24/37). The most frequently immunogenic peptides were MAGE-A3281-295 (49 %) and tyrosinase386-406 (32 %). Responses were not limited to HLA restrictions originally described. Vaccine-associated CD8(+) T cell responses against class I-restricted peptides were observed in 45 % (5/11) of evaluable participants. The 6MHP vaccine induces both CD4(+) and CD8(+) T cell responses against melanoma antigens. CD4(+) T cell responses were detected beyond reported HLA-DR restrictions. Induction of CD8(+) T cell responses suggests epitope spreading and systemic activity mediated at the tumor site.

Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity.

PubMed

Ichikawa, Kosuke; Kagamu, Hiroshi; Koyama, Kenichi; Miyabayashi, Takao; Koshio, Jun; Miura, Satoru; Watanabe, Satoshi; Yoshizawa, Hirohisa; Narita, Ichiei

2012-09-21

MHC class I-restricted peptide-based vaccination therapies have been conducted to treat cancer patients, because CD8⁺ CTL can efficiently induce apoptosis of tumor cells in an MHC class I-restricted epitope-specific manner. Interestingly, clinical responders are known to demonstrate reactivity to epitopes other than those used for vaccination; however, the mechanism underlying how antitumor T cells with diverse specificity are induced is unclear. In this study, we demonstrated that dendritic cells (DCs) that engulfed apoptotic tumor cells in the presence of non-tumor MHC class II-restricted epitope peptides, OVA(323-339), efficiently presented tumor-associated antigens upon effector-dominant CD4⁺ T cell balance against regulatory T cells (Treg) for the OVA(323-339) epitope. Th1 and Th17 induced tumor-associated antigens presentation of DC, while Th2 ameliorated tumor-antigen presentation for CD8⁺ T cells. Blocking experiments with anti-IL-23p19 antibody and anti-IL-23 receptor indicated that an autocrine mechanism of IL-23 likely mediated the diverted tumor-associated antigens presentation of DC. Tumor-associated antigens presentation of DC induced by OVA(323-339) epitope-specific CD4⁺ T cells resulted in facilitated antitumor immunity in both priming and effector phase in vivo. Notably, this immunotherapy did not require pretreatment to reduce Treg induced by tumor. This strategy may have clinical implications for designing effective antitumor immunotherapies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of oestradiol and pathogen-associated molecular patterns on class II-mediated antigen presentation and immunomodulatory molecule expression in the mouse female reproductive tract

PubMed Central

Ochiel, Daniel O; Rossoll, Richard M; Schaefer, Todd M; Wira, Charles R

2012-01-01

Cells of the female reproductive tract (FRT) can present antigen to naive and memory T cells. However, the effects of oestrogen, known to modulate immune responses, on antigen presentation in the FRT remain undefined. In the present study, DO11.10 T-cell antigen receptor transgenic mice specific for the class II MHC-restricted ovalbumin (OVA) 323–339 peptide were used to study the effects of oestradiol and pathogen-associated molecular patterns on antigen presentation in the FRT. We report here that oestradiol inhibited antigen presentation of OVA by uterine epithelial cells, uterine stromal cells and vaginal cells to OVA-specific memory T cells. When ovariectomized animals were treated with oestradiol for 1 or 3 days, antigen presentation was decreased by 20–80%. In contrast, incubation with PAMP increased antigen presentation by epithelial cells (Pam3Cys), stromal cells (peptidoglycan, Pam3Cys) and vaginal cells (Pam3Cys). In contrast, CpG inhibited both stromal and vaginal cell antigen presentation. Analysis of mRNA expression by reverse transcription PCR indicated that oestradiol inhibited CD40, CD80 and class II in the uterus and CD40, CD86 and class II in the vagina. Expression in isolated uterine and vaginal cells paralleled that seen in whole tissues. In contrast, oestradiol increased polymeric immunoglobulin receptor mRNA expression in the uterus and decreased it in the vagina. These results indicate that antigen-presenting cells in the uterus and vagina are responsive to oestradiol, which inhibits antigen presentation and co-stimulatory molecule expression. Further, these findings suggest that antigen-presenting cells in the uterus and vagina respond to selected Toll-like receptor agonists with altered antigen presentation. PMID:22043860

Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2▿

PubMed Central

Barrionuevo, Paula; Cassataro, Juliana; Delpino, M. Victoria; Zwerdling, Astrid; Pasquevich, Karina A.; Samartino, Clara García; Wallach, Jorge C.; Fossati, Carlos A.; Giambartolomei, Guillermo H.

2008-01-01

The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-γ)-producing CD4+ T lymphocytes are poorly understood. We report here that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen (Ag) processing. Heat-killed B. abortus (HKBA) also induced both these phenomena, indicating the independence of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation and IFN-γ production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection. PMID:17984211

Dietary sodium restriction below 2 gram per day predicted shorter event-free survival in patients with mild heart failure

PubMed Central

Song, Eun Kyeung; Moser, Debra K.; Dunbar, Sandra B.; Pressler, Susan J.; Lennie, Terry A.

2015-01-01

Background Despite a growing recognition that a strict low sodium diet may not be warranted in compensated heart failure (HF) patients, the link between sodium restriction below 2g/day and health outcomes is unknown in patients at different levels of HF severity. Purpose To compare differences in event-free survival among patients with < 2g/day, 2–3g/day, or > 3g/day sodium intake stratified by New York Heart Association (NYHA) class. Method A total of 244 patients with HF completed a four-day food diary to measure daily sodium intake. All-cause hospitalization or death for a median of 365follow-up days and covariates on age, gender, etiology, body mass index, NYHA class, ejection fraction, total comorbidity score, the presence of ankle edema, and prescribed medications were determined by patient interview and medical record review. Hierarchical Cox hazard regression was used to address the purpose. Results In NYHA class I/II (n=134), patients with < 2g/day sodium intake had a 3.7-times higher risk (p = .025), while patients with > 3g/day sodium intake had a 0.4-times lower risk (p = .047) for hospitalization or death than those with 2–3g/day sodium intake after controlling for covariates. In NYHA class III/IV (n=110), > 3g/day sodium intake predicted shorter event-free survival (p = .044), whereas there was no difference in survival curves between patients with < 2g/day and those with 2–3g/day sodium intake. Conclusion Sodium restriction below 2g/day is not warranted in mild HF patients, whereas excessive sodium intake above 3g/day may be harmful in moderate to severe HF patients. PMID:24366983

MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes, and is influenced by melanosomes1

PubMed Central

Robila, Valentina; Ostankovitch, Marina; Altrich-VanLith, Michelle L.; Theos, Alexander C.; Drover, Sheila; Marks, Michael S.; Restifo, Nicholas; Engelhard, Victor H.

2009-01-01

Many human solid tumors express MHC II molecules, and proteins normally localized to melanosomes give rise to MHC II restricted epitopes in melanoma. However, the pathways by which this occurs have not been defined. We analyzed the processing of one such epitope, gp10044-59, derived from gp100/Pmel17. In melanomas that have down-regulated components of the melanosomal pathway, but constitutively express HLA-DR*0401, the majority of gp100 is sorted to LAMP-1hi/MHC II+ late endosomes. Using mutant gp100 molecules with altered intracellular trafficking, we demonstrate that endosomal localization is necessary for gp10044-59 presentation. By depletion of the AP2 adaptor protein using siRNA, we demonstrate that gp100 protein internalized from the plasma membrane to such endosomes is a major source for gp10044-59 epitope production. Gp100 trapped in early endosomes gives rise to epitopes that are indistinguishable from those produced in late endosomes but their production is less sensitive to inhibition of lysosomal proteases. In melanomas containing melanosomes, gp100 is underrepresented in late endosomes, and accumulates in stage II melanosomes devoid of MHC II molecules. Gp10044-59 presentation is dramatically reduced, and processing occurs entirely in early endosomes / stage I melanosomes. This suggests that melanosomes are inefficient antigen processing compartments. Thus, melanoma de-differentiation may be accompanied by increased presentation of MHC II restricted epitopes from gp100 and other melanosome-localized proteins, leading to enhanced immune recognition. PMID:19017974

Dentoskeletal changes induced by the Jasper jumper and the activator-headgear combination appliances followed by fixed orthodontic treatment.

PubMed

Lima, Karina Jerônimo Rodrigues Santiago de; Henriques, José Fernando Castanha; Janson, Guilherme; Pereira, Suelen Cristina da Costa; Neves, Leniana Santos; Cançado, Rodrigo Hermont

2013-05-01

The aim of this study was to compare the dentoskeletal changes of patients with Class II Division 1 malocclusion treated with either the Jasper jumper appliance or the activator-headgear combination, both associated with fixed appliances. The sample comprised 72 subjects with Class II Division 1 malocclusion divided into 3 groups: group 1 included 25 subjects treated with fixed appliances and the force modules of the Jasper jumper at an initial mean age of 12.72 years, group 2 included 25 subjects treated with the activator-headgear combination followed by fixed appliances at an initial mean age of 11.07 years, and group 3 included 22 untreated subjects at an initial mean age of 12.67 years. Initial cephalometric characteristics and dentoskeletal changes were compared with analysis of variance. Both experimental groups had similar dentoskeletal changes: restrictive effect on the maxilla, clockwise mandibular rotation and a slight increase in anterior face height, retrusion of the maxillary incisors, distalization of the maxillary molars, protrusion of the mandibular incisors, extrusion of the mandibular molars, and significant improvements of the maxillomandibular relationship, overjet, overbite, and the molar relationship. The effects of the Jasper jumper and the activator-headgear combination followed by fixed orthodontic appliances were similar in Class II malocclusion treatment. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

HLA-DP, HLA-DQ, and HLA-DR-restricted epitopes in GRA5 of toxoplasma gondii strains

NASA Astrophysics Data System (ADS)

Haryati, S.; Sari, Y.; Prasetyo, A. A.; Sariyatun, R.

2016-01-01

The dense granular (GRA) proteins of Toxoplasma gondii(T. gondii) have been demonstrated as potential sources of T. gondii vaccine antigens. However, data of the GRA5 protein are limited. This study analyzed twenty-one complete GRA5 sequences of T. gondii GT1, RH, ME49, VEG, MAS, RUB, FOU, p89, VAND, and GAB2-2007-GAL-DOM2 strains to identify potential epitopes restricted by Major Histocompatibility Complex class II (MHC- II) molecules (human leukocyte antigen (HLA)-DP, HLA-DQ, and HLA-DR) in the protein. In all T. gondii strains, peptides positioned at amino acid (aa) 15-29, 16-30, 17-31, 18-32, 19-33, 83-97, 84-98, 86-100, 87-101, 89-103, and 90-104 were predicted to pose high affinity and binding with HLA-DRB1*0101, HLA-DRB1*0301 (DR17), HLA-DRB1*0401 (DR4Dw4), HLA-DRB1*0701, HLA-DRB1*1101, HLA-DRB1*1501 (DR2b), and/or HLA-DRB5*0101. Considering the epitope's affinity, ligation strength, and hydrophilicity, LRLLRRRRRRAIQEE sequence (aa 90-104) restricted by HLA-DRB1*0101, HlA- DRB1*0301 (DR17), and HLA-DRB1*0401 (DR4Dw4) was considered as the most potential MHC-II epitope in GRA5 of T. gondii. These results would be useful for studies concerning in developing T. gondii vaccine and diagnostic method.

Human leucocyte antigen class I-redirected anti-tumour CD4+ T cells require a higher T cell receptor binding affinity for optimal activity than CD8+ T cells.

PubMed

Tan, M P; Dolton, G M; Gerry, A B; Brewer, J E; Bennett, A D; Pumphrey, N J; Jakobsen, B K; Sewell, A K

2017-01-01

CD4 + T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4 + T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4 + T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4 + cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4 + and CD8 + T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4 + T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4 + T cells than CD8 + T cells. These results indicate that the CD4 + T cell component of current adoptive therapies using TCRs optimized for CD8 + T cells is below par and that there is room for substantial improvement. © 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation.

PubMed

Landais, Elise; Romagnoli, Pablo A; Corper, Adam L; Shires, John; Altman, John D; Wilson, Ian A; Garcia, K Christopher; Teyton, Luc

2009-12-15

Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examined each parameter critical for the production of pMHCT-2 using the I-A(d)-OVA system as a model. Through this process, the geometry of peptide-MHC display by avidin tetramers was examined, as well as the stability of rMHC molecules. However, we discovered that the most important factor limiting the reactivity of pMHCT-2 was the display of peptides. Indeed, long peptides, as presented by MHC class II molecules, can be bound to I-A/HLA-DQ molecules in more than one register, as suggested by structural studies. This mode of anchorless peptide binding allows the selection of a broader repertoire on single peptides and should favor anti-infectious immune responses. Thus, beyond the technical improvements that we propose, the redesign of pMHCT-2 will give us the tools to evaluate the real size of the CD4 T cell repertoire and help us in the production and testing of new vaccines.

The spliced leader RNA gene array in phloem-restricted plant trypanosomatids (Phytomonas) partitions into two major groupings: epidemiological implications.

PubMed

Dollet, M; Sturm, N R; Campbell, D A

2001-03-01

The arbitrary genus Phytomonas includes a biologically diverse group of kinetoplastids that live in a wide variety of plant environments. To understand better the subdivisions within the phytomonads and the variability within groups, the exon, intron and non-transcribed spacer sequences of the spliced leader RNA gene were compared among isolates of the phloem-restricted members. A total of 29 isolates associated with disease in coconut, oil palm and red ginger (Alpinia purpurata, Zingibreaceae) were examined, all originating from plantations in South America and the Caribbean over a 12-year period. Analysis of non-transcribed spacer sequences revealed 2 main groups, I and II; group II could be further subdivided into 2 subgroups, IIa and Ilb. Three classes of spliced leader (SL) RNA gene were seen, with SLI corresponding to group I, SLIIa to group lIa, and SLIIb to group IIb. Two isolates showed some characteristics of both major groups. Group-specific oligonucleotide probes for hybridization studies were tested, and a multiplex amplification scheme was devised to allow direct differentiation between the 2 major groups of phloem-restricted Phytomonas. These results provide tools for diagnostic and molecular epidemiology of plant trypanosomes that are pathogenic for commercially important flowers and palms.

Technical performance score is associated with outcomes after the Norwood procedure.

PubMed

Nathan, Meena; Sleeper, Lynn A; Ohye, Richard G; Frommelt, Peter C; Caldarone, Christopher A; Tweddell, James S; Lu, Minmin; Pearson, Gail D; Gaynor, J William; Pizarro, Christian; Williams, Ismee A; Colan, Steven D; Dunbar-Masterson, Carolyn; Gruber, Peter J; Hill, Kevin; Hirsch-Romano, Jennifer; Jacobs, Jeffrey P; Kaltman, Jonathan R; Kumar, S Ram; Morales, David; Bradley, Scott M; Kanter, Kirk; Newburger, Jane W

2014-11-01

The technical performance score (TPS) has been reported in a single center study to predict the outcomes after congenital cardiac surgery. We sought to determine the association of the TPS with outcomes in patients undergoing the Norwood procedure in the Single Ventricle Reconstruction trial. We calculated the TPS (class 1, optimal; class 2, adequate; class 3, inadequate) according to the predischarge echocardiograms analyzed in a core laboratory and unplanned reinterventions that occurred before discharge from the Norwood hospitalization. Multivariable regression examined the association of the TPS with interval to first extubation, Norwood length of stay, death or transplantation, unplanned postdischarge reinterventions, and neurodevelopment at 14 months old. Of 549 patients undergoing a Norwood procedure, 356 (65%) had an echocardiogram adequate to assess atrial septal restriction or arch obstruction or an unplanned reintervention, enabling calculation of the TPS. On multivariable regression, adjusting for preoperative variables, a better TPS was an independent predictor of a shorter interval to first extubation (P=.019), better transplant-free survival before Norwood discharge (P<.001; odds ratio, 9.1 for inadequate vs optimal), shorter hospital length of stay (P<.001), fewer unplanned reinterventions between Norwood discharge and stage II (P=.004), and a higher Bayley II psychomotor development index at 14 months (P=.031). The TPS was not associated with transplant-free survival after Norwood discharge, unplanned reinterventions after stage II, or the Bayley II mental development index at 14 months. TPS is an independent predictor of important outcomes after Norwood and could serve as a tool for quality improvement. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

Systematic prediction of control proteins and their DNA binding sites

PubMed Central

Sorokin, Valeriy; Severinov, Konstantin; Gelfand, Mikhail S.

2009-01-01

We present here the results of a systematic bioinformatics analysis of control (C) proteins, a class of DNA-binding regulators that control time-delayed transcription of their own genes as well as restriction endonuclease genes in many type II restriction-modification systems. More than 290 C protein homologs were identified and DNA-binding sites for ∼70% of new and previously known C proteins were predicted by a combination of phylogenetic footprinting and motif searches in DNA upstream of C protein genes. Additional analysis revealed that a large proportion of C protein genes are translated from leaderless RNA, which may contribute to time-delayed nature of genetic switches operated by these proteins. Analysis of genetic contexts of newly identified C protein genes revealed that they are not exclusively associated with restriction-modification genes; numerous instances of associations with genes originating from mobile genetic elements were observed. These instances might be vestiges of ancient horizontal transfers and indicate that during evolution ancestral restriction-modification system genes were the sites of mobile elements insertions. PMID:19056824

Evidence for idiotypic- and antiidiotypic B-B cellular interaction with the use of cloned antiidiotypic B cell line.

PubMed

Bitoh, S; Fujimoto, S; Yamamoto, H

1990-03-15

Immunization of BALB/c mice with MOPC104E myeloma protein induces antiidiotypic B lymphocytes that have Id-specific enhancing activity on antibody production. The B-B cell interaction was restricted to both Igh and class II MHC. However, anti-Thy-1 and C-treated splenic B cells were maintained for more than 1 y in a mixture of Con A-stimulated splenocyte culture supernatant and synthetic medium. In applying the long term culture method, we have established a cloned B cell line named B19-1d, B19-1d cells are specific to MOPC104E or J558 cross-reactive Id and they express surface mu, lambda but no Ly-1. B19-1d do not spontaneously secrete Ig but produce them upon stimulation with bacterial LPS. The effect of B19-1d cell line on idiotypic antibody production was tested. Addition of only 10 to 100 B19-1d cells into dextran-immune B cell culture greatly enhanced the Id+ antidextran antibody responses. On the contrary, the antidextran antibody production was suppressed by the higher doses of B19-1d cells. The effective cooperation between dextran-immune B cells and B19-1d cloned B cells was restricted to class II MHC. The role of idiotypic- and antiidiotypic B-B cell interaction in immune regulation and repertoire generation was suggested.

Isonitrile Formation by a Non-heme Iron(II)-Dependent Oxidase/Decarboxylase.

PubMed

Harris, Nicholas; Born, David; Cai, Wenlong; Huang, Yaobing; Martin, Joelle; Khalaf, Ryan; Drennan, Catherine; Zhang, Wenjun

2018-06-15

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We here provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, members of which are critical for the virulence of pathogenic mycobacteria. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathological and non-pathological variants of restrictive eating behaviors in middle childhood: A latent class analysis.

PubMed

Schmidt, Ricarda; Vogel, Mandy; Hiemisch, Andreas; Kiess, Wieland; Hilbert, Anja

2018-08-01

Although restrictive eating behaviors are very common during early childhood, their precise nature and clinical correlates remain unclear. Especially, there is little evidence on restrictive eating behaviors in older children and their associations with children's shape concern. The present population-based study sought to delineate subgroups of restrictive eating patterns in N = 799 7-14 year old children. Using Latent Class Analysis, children were classified based on six restrictive eating behaviors (for example, picky eating, food neophobia, and eating-related anxiety) and shape concern, separately in three age groups. For cluster validation, sociodemographic and objective anthropometric data, parental feeding practices, and general and eating disorder psychopathology were used. The results showed a 3-cluster solution across all age groups: an asymptomatic class (Cluster 1), a class with restrictive eating behaviors without shape concern (Cluster 2), and a class showing restrictive eating behaviors with prominent shape concern (Cluster 3). The clusters differed in all variables used for validation. Particularly, the proportion of children with symptoms of avoidant/restrictive food intake disorder was greater in Cluster 2 than Clusters 1 and 3. The study underlined the importance of considering shape concern to distinguish between different phenotypes of children's restrictive eating patterns. Longitudinal data are needed to evaluate the clusters' predictive effects on children's growth and development of clinical eating disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety Precautions and Operating Procedures in an (A)BSL-4 Laboratory: 2. General Practices.

PubMed

Mazur, Steven; Holbrook, Michael R; Burdette, Tracey; Joselyn, Nicole; Barr, Jason; Pusl, Daniela; Bollinger, Laura; Coe, Linda; Jahrling, Peter B; Lackemeyer, Matthew G; Wada, Jiro; Kuhn, Jens H; Janosko, Krisztina

2016-10-03

Work in a biosafety level 4 (BSL-4) containment laboratory requires time and great attention to detail. The same work that is done in a BSL-2 laboratory with non-high-consequence pathogens will take significantly longer in a BSL-4 setting. This increased time requirement is due to a multitude of factors that are aimed at protecting the researcher from laboratory-acquired infections, the work environment from potential contamination and the local community from possible release of high-consequence pathogens. Inside the laboratory, movement is restricted due to air hoses attached to the mandatory full-body safety suits. In addition, disinfection of every item that is removed from Class II biosafety cabinets (BSCs) is required. Laboratory specialists must be trained in the practices of the BSL-4 laboratory and must show high proficiency in the skills they are performing. The focus of this article is to outline proper procedures and techniques to ensure laboratory biosafety and experimental accuracy using a standard viral plaque assay as an example procedure. In particular, proper techniques to work safely in a BSL-4 environment when performing an experiment will be visually emphasized. These techniques include: setting up a Class II BSC for experiments, proper cleaning of the Class II BSC when finished working, waste management and safe disposal of waste generated inside a BSL-4 laboratory, and the removal of inactivated samples from inside a BSL-4 laboratory to the BSL-2 laboratory.

Sex-specific effect of endothelin in the blood pressure response to acute angiotensin II in growth-restricted rats

PubMed Central

Intapad, Suttira; Ojeda, Norma B.; Varney, Elliott; Royals, Thomas P.; Alexander, Barbara T.

2015-01-01

The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhanced renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 nanogram/kilogram/minute for 30 minutes) with and without the endothelin type-A receptor antagonist, ABT 627(10 nanogram/kilogram/minute for 30 minutes), in rats pretreated with enalapril (250 milligram/Liter for one week) to normalize the endogenous renin angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline following endothelin type-A receptor blockade suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure. PMID:26459423

A vaccine targeting mutant IDH1 induces antitumour immunity.

PubMed

Schumacher, Theresa; Bunse, Lukas; Pusch, Stefan; Sahm, Felix; Wiestler, Benedikt; Quandt, Jasmin; Menn, Oliver; Osswald, Matthias; Oezen, Iris; Ott, Martina; Keil, Melanie; Balß, Jörg; Rauschenbach, Katharina; Grabowska, Agnieszka K; Vogler, Isabel; Diekmann, Jan; Trautwein, Nico; Eichmüller, Stefan B; Okun, Jürgen; Stevanović, Stefan; Riemer, Angelika B; Sahin, Ugur; Friese, Manuel A; Beckhove, Philipp; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael

2014-08-21

Monoallelic point mutations of isocitrate dehydrogenase type 1 (IDH1) are an early and defining event in the development of a subgroup of gliomas and other types of tumour. They almost uniformly occur in the critical arginine residue (Arg 132) in the catalytic pocket, resulting in a neomorphic enzymatic function, production of the oncometabolite 2-hydroxyglutarate (2-HG), genomic hypermethylation, genetic instability and malignant transformation. More than 70% of diffuse grade II and grade III gliomas carry the most frequent mutation, IDH1(R132H) (ref. 3). From an immunological perspective, IDH1(R132H) represents a potential target for immunotherapy as it is a tumour-specific potential neoantigen with high uniformity and penetrance expressed in all tumour cells. Here we demonstrate that IDH1(R132H) contains an immunogenic epitope suitable for mutation-specific vaccination. Peptides encompassing the mutated region are presented on major histocompatibility complexes (MHC) class II and induce mutation-specific CD4(+) T-helper-1 (TH1) responses. CD4(+) TH1 cells and antibodies spontaneously occurring in patients with IDH1(R132H)-mutated gliomas specifically recognize IDH1(R132H). Peptide vaccination of mice devoid of mouse MHC and transgenic for human MHC class I and II with IDH1(R132H) p123-142 results in an effective MHC class II-restricted mutation-specific antitumour immune response and control of pre-established syngeneic IDH1(R132H)-expressing tumours in a CD4(+) T-cell-dependent manner. As IDH1(R132H) is present in all tumour cells of these slow-growing gliomas, a mutation-specific anti-IDH1(R132H) vaccine may represent a viable novel therapeutic strategy for IDH1(R132H)-mutated tumours.

MHC class II B diversity in blue tits: a preliminary study.

PubMed

Aguilar, Juan Rivero-de; Schut, Elske; Merino, Santiago; Martínez, Javier; Komdeur, Jan; Westerdahl, Helena

2013-07-01

In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigated using both PCR-based methods and unamplified genomic DNA with restriction fragment length polymorphism (RFLP) and southern blots. A total of 13 different exon 2 sequences were obtained independently from DNA and/or RNA, thus confirming gene transcription and likely functionality of the genes. Nine out of 13 alleles were found in more than one country, and two alleles appeared in all countries. Positive selection was detected in the region coding for the peptide binding region (PBR). A maximum of three alleles per individual was detected by sequencing and the RFLP pattern consisted of 4-7 fragments, indicating a minimum number of 2-4 loci per individual. A phylogenetic analysis, demonstrated that the blue tit sequences are divergent compared to sequences from other passerines resembling a different MHC lineage than those possessed by most passerines studied to date.

MHC class II B diversity in blue tits: a preliminary study

PubMed Central

Aguilar, Juan Rivero-de; Schut, Elske; Merino, Santiago; Martínez, Javier; Komdeur, Jan; Westerdahl, Helena

2013-01-01

In this study, we partly characterize major histocompatibility complex (MHC) class II B in the blue tit (Cyanistes caeruleus). A total of 22 individuals from three different European locations: Spain, The Netherlands, and Sweden were screened for MHC allelic diversity. The MHC genes were investigated using both PCR-based methods and unamplified genomic DNA with restriction fragment length polymorphism (RFLP) and southern blots. A total of 13 different exon 2 sequences were obtained independently from DNA and/or RNA, thus confirming gene transcription and likely functionality of the genes. Nine out of 13 alleles were found in more than one country, and two alleles appeared in all countries. Positive selection was detected in the region coding for the peptide binding region (PBR). A maximum of three alleles per individual was detected by sequencing and the RFLP pattern consisted of 4–7 fragments, indicating a minimum number of 2–4 loci per individual. A phylogenetic analysis, demonstrated that the blue tit sequences are divergent compared to sequences from other passerines resembling a different MHC lineage than those possessed by most passerines studied to date. PMID:23919136

The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.

PubMed

Fédry, Juliette; Liu, Yanjie; Péhau-Arnaudet, Gérard; Pei, Jimin; Li, Wenhao; Tortorici, M Alejandra; Traincard, François; Meola, Annalisa; Bricogne, Gérard; Grishin, Nick V; Snell, William J; Rey, Félix A; Krey, Thomas

2017-02-23

Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and protists (including important human pathogens like Plasmodium)-suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Recovery of known T-cell epitopes by computational scanning of a viral genome

NASA Astrophysics Data System (ADS)

Logean, Antoine; Rognan, Didier

2002-04-01

A new computational method (EpiDock) is proposed for predicting peptide binding to class I MHC proteins, from the amino acid sequence of any protein of immunological interest. Starting from the primary structure of the target protein, individual three-dimensional structures of all possible MHC-peptide (8-, 9- and 10-mers) complexes are obtained by homology modelling. A free energy scoring function (Fresno) is then used to predict the absolute binding free energy of all possible peptides to the class I MHC restriction protein. Assuming that immunodominant epitopes are usually found among the top MHC binders, the method can thus be applied to predict the location of immunogenic peptides on the sequence of the protein target. When applied to the prediction of HLA-A*0201-restricted T-cell epitopes from the Hepatitis B virus, EpiDock was able to recover 92% of known high affinity binders and 80% of known epitopes within a filtered subset of all possible nonapeptides corresponding to about one tenth of the full theoretical list. The proposed method is fully automated and fast enough to scan a viral genome in less than an hour on a parallel computing architecture. As it requires very few starting experimental data, EpiDock can be used: (i) to predict potential T-cell epitopes from viral genomes (ii) to roughly predict still unknown peptide binding motifs for novel class I MHC alleles.

MHC class II expression in lung cancer.

PubMed

He, Yayi; Rozeboom, Leslie; Rivard, Christopher J; Ellison, Kim; Dziadziuszko, Rafal; Yu, Hui; Zhou, Caicun; Hirsch, Fred R

2017-10-01

Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). Seven (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were found to be MHC Class II positive. We assessed 139 lung cancer samples available in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly lower than that on TILs in NSCLC (P＜0.001). MHC Class II was also assessed in an additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland. Patients with positive staining of MHC Class II on TILs had longer regression-free survival (RFS) and overall survival (OS) than those whose TILs were MHC Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556-1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629-2.151, P=0.014). MHC Class II was expressed both in NSCLC cell lines and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs. Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC. Copyright © 2017. Published by Elsevier B.V.

Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8α+ dendritic cells.

PubMed

Parekh, Vrajesh V; Pabbisetty, Sudheer K; Wu, Lan; Sebzda, Eric; Martinez, Jennifer; Zhang, Jianhua; Van Kaer, Luc

2017-08-01

The class III PI3K Vacuolar protein sorting 34 (Vps34) plays a role in both canonical and noncanonical autophagy, key processes that control the presentation of antigens by dendritic cells (DCs) to naive T lymphocytes. We generated DC-specific Vps34 -deficient mice to assess the contribution of Vps34 to DC functions. We found that DCs from these animals have a partially activated phenotype, spontaneously produce cytokines, and exhibit enhanced activity of the classic MHC class I and class II antigen-presentation pathways. Surprisingly, these animals displayed a defect in the homeostatic maintenance of splenic CD8α + DCs and in the capacity of these cells to cross-present cell corpse-associated antigens to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor. Importantly, mice deficient in the Vps34-associated protein Rubicon, which is critical for a noncanonical form of autophagy called "Light-chain 3 (LC3)-associated phagocytosis" (LAP), lacked such defects. Finally, consistent with their defect in the cross-presentation of apoptotic cells, DC-specific Vps34 -deficient animals developed increased metastases in response to challenge with B16 melanoma cells. Collectively, our studies have revealed a critical role of Vps34 in the regulation of CD8α + DC homeostasis and in the capacity of these cells to process and present antigens associated with apoptotic cells to MHC class I-restricted T cells. Our findings also have important implications for the development of small-molecule inhibitors of Vps34 for therapeutic purposes.

25 CFR 522.10 - Individually owned class II and class III gaming operations other than those operating on...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II and class III gaming... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.10 Individually owned class II and class III...

Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

USGS Publications Warehouse

Minias, Piotr; Bateson, Zachary W.; Whittingham, Linda A.; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O.

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

Contrasting evolutionary histories of MHC class I and class II loci in grouse—effects of selection and gene conversion

PubMed Central

Minias, P; Bateson, Z W; Whittingham, L A; Johnson, J A; Oyler-McCance, S; Dunn, P O

2016-01-01

Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens. PMID:26860199

EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses.

PubMed

Molero-Abraham, Magdalena; Glutting, John-Paul; Flower, Darren R; Lafuente, Esther M; Reche, Pedro A

2015-01-01

Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes.

EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses

PubMed Central

Molero-Abraham, Magdalena; Glutting, John-Paul; Flower, Darren R.; Lafuente, Esther M.; Reche, Pedro A.

2015-01-01

Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. We recognized 8,106, and 8,483 unique class I and class II MHC-restricted T-cell epitopes that are shared by all mentioned orthopoxviruses. Subsequently, we developed an immunological resource, EPIPOX, upon the predicted T-cell epitome. EPIPOX is freely available online and it has been designed to facilitate reverse vaccinology. Thus, EPIPOX includes key epitope-focused protein annotations: time point expression, presence of leader and transmembrane signals, and known location on outer membrane structures of the infective viruses. These features can be used to select specific T-cell epitopes suitable for experimental validation restricted by single MHC alleles, as combinations thereof, or by MHC supertypes. PMID:26605344

Body talk: students' identity construction while discussing a socioscientific issue

NASA Astrophysics Data System (ADS)

Ideland, Malin; Malmberg, Claes

2012-06-01

Vision II school science is often stated to be a democratic and inclusive form of science education. But what characterizes the subject who fits into the Vision II school science? Who is the desirable student and who is constructed as ill-fitting? This article explores discourses that structure the Vision II science classroom, and how different students construct their identities inside these discourses. In the article we consider school science as an order of discourses which restricts and enables what is possible to think and say and what subject-positions those are available and non-available. The results show that students' talk about a SSI about body and health is constituted by several discourses. We have analyzed how school science discourse, body discourse and general school discourse are structuring the discussions. But these discourses are used in different ways depending on how the students construct their identities in relation to available subject positions, which are dependent on how students at the same time are "doing" gender and social class. As an example, middle class girls show resistance against SSI-work since the practice is threatening their identity as "successful students". This article uses a sociopolitical perspective in its discussions on inclusion and exclusion in the practice of Vision II. It raises critical issues about the inherited complexity of SSI with meetings and/or collisions between discourses. Even if the empirical results from this qualitative study are situated in specific cultural contexts, they contribute with new questions to ask concerning SSI and Vision II school science.

Enforced OX40 Stimulation Empowers Booster Vaccines to Induce Effective CD4+ and CD8+ T Cell Responses against Mouse Cytomegalovirus Infection

PubMed Central

Panagioti, Eleni; Boon, Louis; Arens, Ramon; van der Burg, Sjoerd H.

2017-01-01

There is an imperative need for effective preventive vaccines against human cytomegalovirus as it poses a significant threat to the immunologically immature, causing congenital disease, and to the immune compromised including transplant recipients. In this study, we examined the efficacy of synthetic long peptides (SLPs) as a CD4+ and CD8+ T cell-eliciting preventive vaccine approach against mouse CMV (MCMV) infection. In addition, the use of agonistic OX40 antibodies to enhance vaccine efficacy was explored. Immunocompetent C57BL/6 mice were vaccinated in a prime-boost vaccination regiment with SLPs comprising various MHC class I- and II-restricted peptide epitopes of MCMV-encoded antigens. Enforced OX40 stimulation resulted in superior MCMV-specific CD4+ as CD8+ T cell responses when applied during booster SLP vaccination. Vaccination with a mixture of SLPs containing MHC class II epitopes and OX40 agonistic antibodies resulted in a moderate reduction of the viral titers after challenge with lytic MCMV infection. Markedly, the combination of SLP vaccines containing both MHC class I and II epitopes plus OX40 activation during booster vaccination resulted in polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD4+ and CD8+ T cell responses that were even higher in magnitude when compared to those induced by the virus, and this resulted in the best containment of virus dissemination. Our results show that the induction of strong T cell responses can be a fundamental component in the design of vaccines against persistent viral infections. PMID:28265272

Molecular Analysis of Bacterial Community Dynamics During Bioaugmentation Studies in a Soil Column and at a Field Test Site

DTIC Science & Technology

2004-06-03

82 4.14 A GelComparII-generated UPGMA clustering dendrogram and corresponding normalized restriction...A GelComparII-generated UPGMA clustering dendrogram and corresponding normalized restriction profiles from the community...A GelComparII-generated UPGMA clustering dendrogram and corresponding normalized restriction profiles from the community

How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases.

PubMed

Kurian, P; Dunston, G; Lindesay, J

2016-02-21

Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme's displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations-a possible signature of quantum entanglement-may be explained by such a mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases

PubMed Central

Kurian, P.; Dunston, G.; Lindesay, J.

2015-01-01

Macroscopic quantum effects in living systems have been studied widely in pursuit of fundamental explanations for biological energy transport and sensing. While it is known that type II endonucleases, the largest class of restriction enzymes, induce DNA double-strand breaks by attacking phosphodiester bonds, the mechanism by which simultaneous cutting is coordinated between the catalytic centers remains unclear. We propose a quantum mechanical model for collective electronic behavior in the DNA helix, where dipole-dipole oscillations are quantized through boundary conditions imposed by the enzyme. Zero-point modes of coherent oscillations would provide the energy required for double-strand breakage. Such quanta may be preserved in the presence of thermal noise by the enzyme’s displacement of water surrounding the DNA recognition sequence. The enzyme thus serves as a decoherence shield. Palindromic mirror symmetry of the enzyme-DNA complex should conserve parity, because symmetric bond-breaking ceases when the symmetry of the complex is violated or when physiological parameters are perturbed from optima. Persistent correlations in DNA across longer spatial separations—a possible signature of quantum entanglement—may be explained by such a mechanism. PMID:26682627

Evaluation of four microbial Class II fructose 1,6-bisphosphate aldolase enzymes for use as biocatalysts.

PubMed

Labbé, Geneviève; de Groot, Sarah; Rasmusson, Timothy; Milojevic, Gorica; Dmitrienko, Gary I; Guillemette, J Guy

2011-12-01

Fructose 1,6-bisphosphate (FBP) aldolase has been used as biocatalyst in the synthesis of several pharmaceutical compounds such as monosaccharides and analogs. Is has been suggested that microbial metal-dependant Class II aldolases could be better industrial catalysts than mammalian Class I enzyme because of their greater stability. The Class II aldolases from four microbes were subcloned into the Escherichia coli vector pT7-7, expressed and purified to near homogeneity. The kinetic parameters, temperature stability, pH profile, and tolerance to organic solvents of the Class II enzymes were determined, and compared with the properties of the Class I aldolase from rabbit muscle. Contrary to results obtained previously with the E. coli Class II aldolase, which was reported to be more stable than the mammalian enzyme, other recombinant Class II aldolases were found to be generally less stable than the Class I enzyme, especially in the presence of organic solvents. Class II aldolase from Bacillus cereus showed higher temperature stability than the other enzymes tested, but only the Mycobacterium tuberculosis Class II aldolase had a stability comparable to the Class I mammalian enzyme under assay conditions. The turnover number of the recombinant M. tuberculosis and Magnaporthe grisea Class II type A aldolases was comparable or higher than that of the Class I enzyme. The recombinant B. cereus and Pseudomonas aeruginosa Class II type B aldolases had very low turnover numbers and low metal content, indicating that the E. coli overexpression system may not be suitable for the Class II type B aldolases from these microorganisms. Copyright © 2011 Elsevier Inc. All rights reserved.

Association of SNP variants of MHC Class II DRB gene with thermo-physiological traits in tropical goats.

PubMed

Yakubu, Abdulmojeed; Salako, Adebowale E; De Donato, Marcos; Peters, Sunday O; Takeet, Michael I; Wheto, Mathew; Okpeku, Moses; Imumorin, Ikhide G

2017-02-01

Host defense in vertebrates depend on many secreted regulatory proteins such as major histocompatibility complex (MHC) class II which provide important regulatory and effector functions of T cells. Gene polymorphism in the second exon of Capra-DRB gene in three major Nigerian goat breeds [West African Dwarf (WAD), Red Sokoto (RS), and Sahel (SH)] was analyzed by restriction fragment length polymorphisms (RFLP). Four restriction enzymes, BsaHI, AluI, HaeIII, and SacII, were utilized. The association between the polymorphic sites and some heat tolerance traits were also investigated in a total of 70 WAD, 90 RS, and 50 SH goats. Fourteen different types of alleles identified in the Nigerian goats, four of which were found in the peptide coding region (A57G, Q89R, G104D, and T112I), indicate a high degree of polymorphism at the DRB locus in this species. An obvious excess (P < 0.01) of non-synonymous substitutions than synonymous (dN/dS) in this locus is a reflection of adaptive evolution and positive selection. The phylogenetic trees revealed largely species-wise clustering in DRB gene. BsaHI, AluI, HaeIII, and SacII genotype frequencies were in Hardy-Weinberg equilibrium (P > 0.05), except AluI in RS goats and HaeIII in WAD goats (P < 0.05). The expected heterozygosity (H), which is a measure of gene diversity in the goat populations, ranged from 0.16 to 0.50. Genotypes AA (BsaHI), GG, GC and CC (AluI) and GG, GA, AA (HaeIII) appeared better in terms of heat tolerance. The heat-tolerant ability of SH and RS goats to the hot and humid tropical environment of Nigeria seemed better than that of the WAD goats. Sex effect (P < 0.05) was mainly on pulse rate and heat stress index, while there were varying interaction effects on heat tolerance. Variation at the DRB locus may prove to be important in possible selection and breeding for genetic resistance to heat stress in the tropics.

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2012 CFR

2012-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

25 CFR 547.3 - What are the definitions for this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.3 What are the... Commission. Class II game. The same as “class II gaming” in 25 U.S.C. 2703(7)(A). Class II gaming system. All..., that function together to aid the play of one or more Class II games, including accounting functions...

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography

PubMed Central

Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-01-01

Objective To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. Methods CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Results Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Conclusions Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients. PMID:23814708

Alveolar bone thickness and lower incisor position in skeletal Class I and Class II malocclusions assessed with cone-beam computed tomography.

PubMed

Baysal, Asli; Ucar, Faruk Izzet; Buyuk, Suleyman Kutalmis; Ozer, Torun; Uysal, Tancan

2013-06-01

To evaluate lower incisor position and bony support between patients with Class II average- and high-angle malocclusions and compare with the patients presenting Class I malocclusions. CBCT records of 79 patients were divided into 2 groups according to sagittal jaw relationships: Class I and II. Each group was further divided into average- and high-angle subgroups. Six angular and 6 linear measurements were performed. Independent samples t-test, Kruskal-Wallis, and Dunn post-hoc tests were performed for statistical comparisons. Labial alveolar bone thickness was significantly higher in Class I group compared to Class II group (p = 0.003). Lingual alveolar bone angle (p = 0.004), lower incisor protrusion (p = 0.007) and proclination (p = 0.046) were greatest in Class II average-angle patients. Spongious bone was thinner (p = 0.016) and root apex was closer to the labial cortex in high-angle subgroups when compared to the Class II average-angle subgroup (p = 0.004). Mandibular anterior bony support and lower incisor position were different between average- and high-angle Class II patients. Clinicians should be aware that the range of lower incisor movement in high-angle Class II patients is limited compared to average- angle Class II patients.

Natural Polymorphisms in Tap2 Influence Negative Selection and CD4∶CD8 Lineage Commitment in the Rat

PubMed Central

Tuncel, Jonatan; Haag, Sabrina; Yau, Anthony C. Y.; Norin, Ulrika; Baud, Amelie; Lönnblom, Erik; Maratou, Klio; Ytterberg, A. Jimmy; Ekman, Diana; Thordardottir, Soley; Johannesson, Martina; Gillett, Alan; Stridh, Pernilla; Jagodic, Maja; Olsson, Tomas; Fernández-Teruel, Alberto; Zubarev, Roman A.; Mott, Richard; Aitman, Timothy J.; Flint, Jonathan; Holmdahl, Rikard

2014-01-01

Genetic variation in the major histocompatibility complex (MHC) affects CD4∶CD8 lineage commitment and MHC expression. However, the contribution of specific genes in this gene-dense region has not yet been resolved. Nor has it been established whether the same genes regulate MHC expression and T cell selection. Here, we assessed the impact of natural genetic variation on MHC expression and CD4∶CD8 lineage commitment using two genetic models in the rat. First, we mapped Quantitative Trait Loci (QTLs) associated with variation in MHC class I and II protein expression and the CD4∶CD8 T cell ratio in outbred Heterogeneous Stock rats. We identified 10 QTLs across the genome and found that QTLs for the individual traits colocalized within a region spanning the MHC. To identify the genes underlying these overlapping QTLs, we generated a large panel of MHC-recombinant congenic strains, and refined the QTLs to two adjacent intervals of ∼0.25 Mb in the MHC-I and II regions, respectively. An interaction between these intervals affected MHC class I expression as well as negative selection and lineage commitment of CD8 single-positive (SP) thymocytes. We mapped this effect to the transporter associated with antigen processing 2 (Tap2) in the MHC-II region and the classical MHC class I gene(s) (RT1-A) in the MHC-I region. This interaction was revealed by a recombination between RT1-A and Tap2, which occurred in 0.2% of the rats. Variants of Tap2 have previously been shown to influence the antigenicity of MHC class I molecules by altering the MHC class I ligandome. Our results show that a restricted peptide repertoire on MHC class I molecules leads to reduced negative selection of CD8SP cells. To our knowledge, this is the first study showing how a recombination between natural alleles of genes in the MHC influences lineage commitment of T cells. PMID:24586191

Effect of monoclonal antibodies (MoAb) to class I and class II HLA antigens on lectin- and MoAb OKT3-induced lymphocyte proliferation.

PubMed

Akiyama, Y; Zicht, R; Ferrone, S; Bonnard, G D; Herberman, R B

1985-04-01

We have examined the effect of several monoclonal antibodies (MoAb) to monomorphic determinants of class II HLA antigens, and MoAb to monomorphic determinants of class I HLA antigens and to beta-2-microglobulin (beta 2-mu) on lectin- and MoAb OKT3-induced proliferation of human peripheral blood mononuclear cells (PBMNC) and cultured T cells (CTC). Some, but not all, anti-class II HLA MoAb inhibited the proliferative response of PBMNC to MoAb OKT3 and pokeweed mitogen (PWM). The degree of inhibitory effect varied considerably. This effect was not limited to anti-class II HLA MoAb since anti-class I HLA MoAb and anti-beta 2-mu MoAb also inhibited MoAb OKT3- or PWM-induced proliferative responses. In contrast, the response of PBMNC to phytohemagglutinin (PHA) and concanavalin A (Con A) was not blocked by any anti-class II HLA MoAb. However, some anti-class II HLA MoAb also inhibited the proliferative response of CTC plus allogeneic peripheral blood adherent accessory cells (AC) to PHA or Con A as well as to MoAb OKT3 or PWM. This may be attributable to the substantially greater class II HLA antigen expression by CTC than by fresh lymphocytes. Pretreatment of either CTC or AC with anti-class II HLA MoAb inhibited OKT3-induced proliferation. In contrast, pretreatment of CTC, but not AC, with anti-class I HLA MoAb inhibited the proliferative response of CTC to OKT3. Pretreatment of CTC with anti-class I HLA MoAb inhibited PHA-, Con A and PWM-induced proliferation, to a greater degree than the anti-class II HLA MoAb. It appears as if lymphocyte activation by different mitogens exhibits variable requirements for the presence of cells expressing major histocompatibility determinants. Binding of Ab to membrane markers may interfere with lymphocyte-AC cooperation, perhaps by inhibiting binding of mitogens to their receptors or by interfering with lymphocyte and AC function. We also have examined the role of class II HLA antigens on CTC by depleting class II HLA-positive cells. As expected, elimination of class II HLA-positive AC with anti-class II HLA MoAb plus complement caused a decrease in proliferation of CTC in response to all the mitogens tested. In contrast, elimination of class II HLA-positive CTC was shown to clearly increase proliferation of CTC, perhaps because this may deplete class II HLA-positive suppressor cells.

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor

PubMed Central

Ojeda, Norma B.; Royals, Thomas P.

2013-01-01

This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg−1·min−1) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P < 0.05). Cotreatment with the Rho kinase inhibitor fasudil (33 μg·kg−1·min−1) significantly attenuated these hemodynamic changes (P < 0.05), but it did not abolish the differential increase in blood pressure above baseline, suggesting that the impact of intrauterine growth restriction on blood pressure in intact male growth-restricted rats is independent of Rho kinase. Gonadectomy in conjunction with fasudil returned blood pressure back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats. PMID:23344570

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor.

PubMed

Ojeda, Norma B; Royals, Thomas P; Alexander, Barbara T

2013-04-01

This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg(-1)·min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P < 0.05). Cotreatment with the Rho kinase inhibitor fasudil (33 μg·kg(-1)·min(-1)) significantly attenuated these hemodynamic changes (P < 0.05), but it did not abolish the differential increase in blood pressure above baseline, suggesting that the impact of intrauterine growth restriction on blood pressure in intact male growth-restricted rats is independent of Rho kinase. Gonadectomy in conjunction with fasudil returned blood pressure back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.

Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: are we close to reality?

PubMed Central

Simoni, Y; Diana, J; Ghazarian, L; Beaudoin, L; Lehuen, A

2013-01-01

T cells reactive to lipids and restricted by major histocompatibility complex (MHC) class I-like molecules represent more than 15% of all lymphocytes in human blood. This heterogeneous population of innate cells includes the invariant natural killer T cells (iNK T), type II NK T cells, CD1a,b,c-restricted T cells and mucosal-associated invariant T (MAIT) cells. These populations are implicated in cancer, infection and autoimmunity. In this review, we focus on the role of these cells in autoimmunity. We summarize data obtained in humans and preclinical models of autoimmune diseases such as primary biliary cirrhosis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis and atherosclerosis. We also discuss the promise of NK T cell manipulations: restoration of function, specific activation, depletion and the relevance of these treatments to human autoimmune diseases. PMID:23199318

Immunological Functions of the Membrane Proximal Region of MHC Class II Molecules

PubMed Central

Harton, Jonathan; Jin, Lei; Hahn, Amy; Drake, Jim

2016-01-01

Major histocompatibility complex (MHC) class II molecules present exogenously derived antigen peptides to CD4 T cells, driving activation of naïve T cells and supporting CD4-driven immune functions. However, MHC class II molecules are not inert protein pedestals that simply bind and present peptides. These molecules also serve as multi-functional signaling molecules delivering activation, differentiation, or death signals (or a combination of these) to B cells, macrophages, as well as MHC class II-expressing T cells and tumor cells. Although multiple proteins are known to associate with MHC class II, interaction with STING (stimulator of interferon genes) and CD79 is essential for signaling. In addition, alternative transmembrane domain pairing between class II α and β chains influences association with membrane lipid sub-domains, impacting both signaling and antigen presentation. In contrast to the membrane-distal region of the class II molecule responsible for peptide binding and T-cell receptor engagement, the membrane-proximal region (composed of the connecting peptide, transmembrane domain, and cytoplasmic tail) mediates these “non-traditional” class II functions. Here, we review the literature on the function of the membrane-proximal region of the MHC class II molecule and discuss the impact of this aspect of class II immunobiology on immune regulation and human disease. PMID:27006762

Brucella melitensis T Cell Epitope Recognition in Humans with Brucellosis in Peru

PubMed Central

Cannella, Anthony P.; Arlehamn, Cecilia S. Lindestam; Sidney, John; Patra, Kailash P.; Torres, Katherine; Tsolis, Renee M.; Liang, Li; Felgner, Philip L.; Saito, Mayuko; Gotuzzo, Eduardo; Gilman, Robert H.; Sette, Alessandro

2014-01-01

Brucella melitensis, one of the causative agents of human brucellosis, causes acute, chronic, and relapsing infection. While T cell immunity in brucellosis has been extensively studied in mice, no recognized human T cell epitopes that might provide new approaches to classifying and prognosticating B. melitensis infection have ever been delineated. Twenty-seven pools of 500 major histocompatibility complex class II (MHC-II) restricted peptides were created by computational prediction of promiscuous MHC-II CD4+ T cell derived from the top 50 proteins recognized by IgG in human sera on a genome level B. melitensis protein microarray. Gamma interferon (IFN-γ) and interleukin-5 (IL-5) enzyme-linked immunospot (ELISPOT) analyses were used to quantify and compare Th1 and Th2 responses of leukapheresis-obtained peripheral blood mononuclear cells from Peruvian subjects cured after acute infection (n = 9) and from patients who relapsed (n = 5). Four peptide epitopes derived from 3 B. melitensis proteins (BMEI 1330, a DegP/HtrA protease; BMEII 0029, type IV secretion system component VirB5; and BMEII 0691, a predicted periplasmic binding protein of a peptide transport system) were found repeatedly to produce significant IFN-γ ELISPOT responses in both acute-infection and relapsing patients; none of the peptides distinguished the patient groups. IL-5 responses against the panel of peptides were insignificant. These experiments are the first to systematically identify B. melitensis MHC-II-restricted CD4+ T cell epitopes recognized by the human immune response, with the potential for new approaches to brucellosis diagnostics and understanding the immunopathogenesis related to this intracellular pathogen. PMID:24126518

Analysis of polyhydroxyalkanoate (PHA) synthase gene and PHA-producing bacteria in activated sludge that produces PHA containing 3-hydroxydodecanoate.

PubMed

Yang, Chao; Zhang, Wei; Liu, Ruihua; Zhang, Chi; Gong, Ting; Li, Qiang; Wang, Shufang; Song, Cunjiang

2013-09-01

Activated sludge is an alternative to pure cultures for polyhydroxyalkanoate (PHA) production due to the presence of many PHA-producing bacteria in activated sludge community. In this study, activated sludge was submitted to aerobic dynamic feeding in a sequencing batch reactor. During domestication, the changes of bacterial community structure were observed by terminal restriction fragment length polymorphism analysis. Furthermore, some potential PHA-producing bacteria, such as Thauera, Acinetobacter and Pseudomonas, were identified by denaturing gradient gel electrophoresis analysis. The constructed PHA synthase gene library was analyzed by DNA sequencing. Of the 80 phaC genes obtained, 76 belonged to the Class I PHA synthase, and four to the Class II PHA synthase. Gas chromatography-mass spectrometry analysis showed that PHA produced by activated sludge was composed of three types of monomers: 3-hydroxybutyrate, 3-hydroxyvalerate and 3-hydroxydodecanoate (3HDD). This is the first report of production of medium-chain-length PHAs (PHAMCL ) containing 3HDD by activated sludge. Further studies suggested that a Pseudomonas strain may play an important role in the production of PHAMCL containing 3HDD. Moreover, a Class II PHA synthase was found to have a correlation with the production of 3HDD-containing PHAMCL . © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Temporal Alterations in Vascular Angiotensin Receptors and Vasomotor Response in Offspring of Protein-restricted Rat Dams

PubMed Central

SATHISHKUMAR, Kunju; BALAKRISHNAN, Meena; CHINNATHAMBI, Vijayakumar; GAO, Haijun; YALLAMPALLI, Chandra

2012-01-01

Objective Examine temporal alterations in vascular angiotensin II (ANG II) receptors (AT1R and AT2R) and determine vascular response to ANG II in growth-restricted offspring. Study design Offspring of pregnant rats fed low-protein (6%) and control (20%) diet were compared. Results Prenatal protein restriction reprogrammed AT1aR mRNA expression in males’ mesenteric arteries to cause 1.7- and 2.3-fold increases at 3 and 6 months of age associated with arterial pressure increases of 10 and 33 mmHg, respectively; however, in females, increased AT1aR expression (2-fold) and arterial pressure (15 mmHg) occurred only at 6 months. Prenatal protein restriction did not affect AT2R expression. Losartan abolished hypertension, suggesting that AT1aR plays a primary role in arterial pressure elevation. Vasoconstriction to ANG II was exaggerated in all protein-restricted offspring, with greater potency and efficacy in males. Conclusion Prenatal protein restriction increased vascular AT1R expression and vasoconstriction to ANG II, possibly contributing to programmed hypertension. PMID:22537420

25 CFR 522.5 - Disapproval of a class II ordinance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Disapproval of a class II ordinance. 522.5 Section 522.5 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING ORDINANCE OR RESOLUTION § 522.5 Disapproval of a class II...

Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates

PubMed Central

2013-01-01

Background Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system. Results We discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish. Conclusions Teleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage. PMID:24279922

The overlooked "nonclassical" functions of major histocompatibility complex (MHC) class II antigens in immune and nonimmune cells.

PubMed

Altomonte, M; Pucillo, C; Maio, M

1999-06-01

Besides their "classical" antigenic peptide-presenting activity, major histocompatibility complex (MHC) class II antigens can activate different cellular functions in immune and nonimmune cells. However, this "nonclassical" role and its functional consequences are still substantially overlooked. In this review, we will focus on these alternative functional properties of MHC class II antigens, to reawaken attention to their present and foreseeable immunobiologic and pathogenetic implications. The main issues that will be addressed concern 1) the role of MHC class II molecules as basic components of exchangeable oligomeric protein complexes with intracellular signaling ability; 2) the nonclassical functions of MHC class II antigens in immune cells; 3) the pathogenetic role of MHC class II antigens in inflammatory/autoimmune and infectious disease; and 4) the functional role of MHC class II antigens in solid malignancies.

Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

PubMed

Sloan, M A; Alexandrov, A V; Tegeler, C H; Spencer, M P; Caplan, L R; Feldmann, E; Wechsler, L R; Newell, D W; Gomez, C R; Babikian, V L; Lefkowitz, D; Goldman, R S; Armon, C; Hsu, C Y; Goodin, D S

2004-05-11

To review the use of transcranial Doppler ultrasonography (TCD) and transcranial color-coded sonography (TCCS) for diagnosis. The authors searched the literature for evidence of 1) if TCD provides useful information in specific clinical settings; 2) if using this information improves clinical decision making, as reflected by improved patient outcomes; and 3) if TCD is preferable to other diagnostic tests in these clinical situations. TCD is of established value in the screening of children aged 2 to 16 years with sickle cell disease for stroke risk (Type A, Class I) and the detection and monitoring of angiographic vasospasm after spontaneous subarachnoid hemorrhage (Type A, Class I to II). TCD and TCCS provide important information and may have value for detection of intracranial steno-occlusive disease (Type B, Class II to III), vasomotor reactivity testing (Type B, Class II to III), detection of cerebral circulatory arrest/brain death (Type A, Class II), monitoring carotid endarterectomy (Type B, Class II to III), monitoring cerebral thrombolysis (Type B, Class II to III), and monitoring coronary artery bypass graft operations (Type B to C, Class II to III). Contrast-enhanced TCD/TCCS can also provide useful information in right-to-left cardiac/extracardiac shunts (Type A, Class II), intracranial occlusive disease (Type B, Class II to IV), and hemorrhagic cerebrovascular disease (Type B, Class II to IV), although other techniques may be preferable in these settings.

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

25 CFR 547.8 - What are the minimum technical software standards applicable to Class II gaming systems?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.8 What are the minimum technical software standards applicable to Class II... of Class II games. (a) Player interface displays. (1) If not otherwise provided to the player, the player interface shall display the following: (i) The purchase or wager amount; (ii) Game results; and...

Treatment Effects of Removable Functional Appliances in Pre-Pubertal and Pubertal Class II Patients: A Systematic Review and Meta-Analysis of Controlled Studies

PubMed Central

Perinetti, Giuseppe; Primožič, Jasmina; Franchi, Lorenzo; Contardo, Luca

2015-01-01

Background Treatment effects of removable functional appliances in Class II malocclusion patients according to the pre-pubertal or pubertal growth phase has yet to be clarified. Objectives To assess and compare skeletal and dentoalveolar effects of removable functional appliances in Class II malocclusion treatment between pre-pubertal and pubertal patients. Search methods Literature survey using the Medline, SCOPUS, LILACS and SciELO databases, the Cochrane Library from inception to May 31, 2015. A manual search was also performed. Selection criteria Randomised (RCTs) or controlled clinical trials with a matched untreated control group. No restrictions were set regarding the type of removable appliance whenever used alone. Data collection and analysis For the meta-analysis, cephalometric parameters on the supplementary mandibular growth were the main outcomes, with other cephalometric parameters considered as secondary outcomes. Risk of bias in individual and across studies were evaluated along with sensitivity analysis for low quality studies. Mean differences and 95% confidence intervals for annualised changes were computed according to a random model. Differences between pre-pubertal and pubertal patients were assessed by subgroup analyses. GRADE assessment was performed for the main outcomes. Results Twelve articles (but only 3 RCTs) were included accounting for 8 pre-pubertal and 7 pubertal groups. Overall supplementary total mandibular length and mandibular ramus height were 0.95 mm (0.38, 1.51) and 0.00 mm (-0.52, 0.53) for pre-pubertal patients and 2.91 mm (2.04, 3.79) and 2.18 mm (1.51, 2.86) for pubertal patients, respectively. The subgroup difference was significant for both parameters (p<0.001). No maxillary growth restrain or increase in facial divergence was seen in either subgroup. The GRADE assessment was low for the pre-pubertal patients, and generally moderate for the pubertal patients. Conclusions Taking into account the limited quality and heterogeneity of the included studies, functional treatment by removable appliances may be effective in treating Class II malocclusion with clinically relevant skeletal effects if performed during the pubertal growth phase. PMID:26510187

A comparison of the efficacy of fixed versus removable functional appliances in children with Class II malocclusion: A systematic review.

PubMed

Pacha, Moaiyad Moussa; Fleming, Padhraig S; Johal, Ama

2016-12-01

To systematically compare the efficacy of fixed and removable functional appliances in Class II malocclusion in terms of morphological and patient-centred outcomes. A comprehensive search of electronic databases without language or time restrictions was undertaken, applying a pre-specified search strategy. Supplementary electronic searching of orthodontics journals and references list of included studies was performed. Randomized (RCTs) and controlled (CCTs) clinical trials involving children under 16 years with Class II malocclusion and overjet more than 5mm were included. A range of clinician- and patient-centred outcomes were evaluated and compared. Risk of bias assessment was carried out using the Cochrane Collaboration tool. Only four clinical trials were found to meet our criteria, of which two were RCTs, comparing the Herbst and the Twin Block appliances. Two further CCTs, compared the Activator to the Forsus and the Twin Force Bite Corrector, respectively. One study was assessed to be at unclear and the remaining at high risk of bias, precluding meta-analysis. There was also significant clinical heterogeneity in terms of methodology, type of intervention and the measured outcomes. Both modalities were effective in correcting the overjet with little differences found in cephalometric changes and a shortage of data concerning patient-centred outcomes. There is little evidence concerning the relative effectiveness of fixed and functional appliances or in relation to patient experiences and perceptions of these treatment modalities. Further well-designed clinical trials assessing the relative merits of both clinician- and patient-centred outcomes are needed. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Both positive and negative effects on immune responses by expression of a second class II MHC molecule.

PubMed

Ni, Peggy P; Wang, Yaming; Allen, Paul M

2014-11-01

It is perplexing why vertebrates express a limited number of major histocompatibility complex (MHC) molecules when theoretically, having a greater repertoire of MHC molecules would increase the number of epitopes presented, thereby enhancing thymic selection and T cell response to pathogens. It is possible that any positive effects would either be neutralized or outweighed by negative selection restricting the T cell repertoire. We hypothesize that the limit on MHC number is due to negative consequences arising from expressing additional MHC. We compared T cell responses between B6 mice (I-A(+)) and B6.E(+) mice (I-A(+), I-E(+)), the latter expressing a second class II MHC molecule, I-E(b), due to a monomorphic Eα(k) transgene that pairs with the endogenous I-Eβ(b) chain. First, the naive T cell Vβ repertoire was altered in B6.E(+) thymi and spleens, potentially mediating different outcomes in T cell reactivity. Although the B6 and B6.E(+) responses to hen egg-white lysozyme (HEL) protein immunization remained similar, other immune models yielded differences. For viral infection, the quality of the T cell response was subtly altered, with diminished production of certain cytokines by B6.E(+) CD4(+) T cells. In alloreactivity, the B6.E(+) T cell response was significantly dampened. Finally, we observed markedly enhanced susceptibility to experimental autoimmune encephalomyelitis (EAE) in B6.E(+) mice. This correlated with decreased percentages of nTreg cells, supporting the concept of Tregs exhibiting differential susceptibility to negative selection. Altogether, our data suggest that expressing an additional class II MHC can produce diverse effects, with more severe autoimmunity providing a compelling explanation for limiting the expression of MHC molecules. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification and HLA-tetramer-validation of human CD4+ and CD8+ T cell responses against HCMV proteins IE1 and IE2.

PubMed

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Osterby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette

2014-01-01

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.

Identification and HLA-Tetramer-Validation of Human CD4+ and CD8+ T Cell Responses against HCMV Proteins IE1 and IE2

PubMed Central

Braendstrup, Peter; Mortensen, Bo Kok; Justesen, Sune; Østerby, Thomas; Rasmussen, Michael; Hansen, Andreas Martin; Christiansen, Claus Bohn; Hansen, Morten Bagge; Nielsen, Morten; Vindeløv, Lars; Buus, Søren; Stryhn, Anette

2014-01-01

Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ and CD8+ T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on CD8+ T cell responses against the pp65 phosphoprotein. In this study, we have focused on CD4+ and CD8+ T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-γ ELISpot and in vitro intracellular cytokine secretion assays. The specificities of CD4+ and CD8+ T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one CD4+ and 44 CD8+ T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy. PMID:24760079

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2012 CFR

2012-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

40 CFR 147.3200 - Fort Peck Indian Reservation: Assiniboine & Sioux Tribes-Class II wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

...: Assiniboine & Sioux Tribes-Class II wells. 147.3200 Section 147.3200 Protection of Environment ENVIRONMENTAL... INJECTION CONTROL PROGRAMS Assiniboine and Sioux Tribes § 147.3200 Fort Peck Indian Reservation: Assiniboine & Sioux Tribes—Class II wells. The UIC program for Class II injection wells on all lands within the...

78 FR 24061 - Minimum Technical Standards for Class II Gaming Systems and Equipment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Register that established technical standards for ensuring the integrity of electronic Class II games and aids. 73 FR 60508, Oct. 10, 2008. The technical standards were designed to assist tribal gaming... Class II gaming systems. The standards did not classify which games were Class II games and which games...

40 CFR 147.3400 - Navajo Indian lands-Class II wells.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Navajo Indian lands-Class II wells... Indian Lands § 147.3400 Navajo Indian lands—Class II wells. The UIC program for Class II injection wells... outside those exterior boundaries (collectively referred to as “Navajo Indian lands for which EPA has...

77 FR 37058 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

...] Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance... availability of the draft guidance entitled ``Class II Special Controls Guidance Document: Implanted Blood... blood access devices may comply with the requirement of special controls for class II devices. This...

Differential Transmembrane Domain GXXXG Motif Pairing Impacts Major Histocompatibility Complex (MHC) Class II Structure*

PubMed Central

Dixon, Ann M.; Drake, Lisa; Hughes, Kelly T.; Sargent, Elizabeth; Hunt, Danielle; Harton, Jonathan A.; Drake, James R.

2014-01-01

Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2+ class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2+ I-Ak conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2+ versus Ia.2− I-Ak class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response. PMID:24619409

40 CFR 144.19 - Transitioning from Class II to Class VI.

Code of Federal Regulations, 2011 CFR

2011-07-01

... primary purpose of long-term storage into an oil and gas reservoir must apply for and obtain a Class VI geologic sequestration permit when there is an increased risk to USDWs compared to Class II operations. In... Class II operations and a Class VI permit is required. In order to make this determination the Director...

A Triad of Molecular Regions Contribute to the Formation of Two Distinct MHC Class II Conformers

PubMed Central

Drake, Lisa A.; Drake, James R.

2016-01-01

MHC class II molecules present antigen-derived peptides to CD4 T cells to drive the adaptive immune response. Previous work has established that class II αβ dimers can adopt two distinct conformations, driven by the differential pairing of transmembrane domain GxxxG dimerization motifs. These class II conformers differ in their ability to be loaded with antigen-derived peptide and to effectively engage CD4 T cells. Motif 1 (M1) paired I-Ak class II molecules are efficiently loaded with peptides derived from the processing of B cell receptor-bound antigen, have unique B cell signaling properties and high T cell stimulation activity. The 11-5.2 mAb selectively binds M1 paired I-Ak class II molecules. However, the molecular determinants of 11-5.2 binding are currently unclear. Here, we report the ability of a human class II transmembrane domain to drive both M1 and M2 class II conformer formation. Protease sensitivity analysis further strengthens the idea that there are conformational differences between the extracellular domains of M1 and M2 paired class II. Finally, MHC class II chain alignments and site directed mutagenesis reveals a triad of molecular regions that contributes to 11-5.2 mAb binding. In addition to transmembrane GxxxG motif domain pairing, 11-5.2 binding is influenced directly by α chain residue Glu-71 and indirectly by the region around the inter-chain salt bridge formed by α chain Arg-52 and β chain Glu-86. These findings provide insight into the complexity of 11-5.2 mAb recognition of the M1 paired I-Ak class II conformer and further highlight the molecular heterogeneity of peptide-MHC class II complexes that drive T cell antigen recognition. PMID:27148821

Maxillary and mandibular contribution to the establishment of class II malocclusion in an adult Lebanese population.

PubMed

El Hajj, Nadine; Bassil-Nassif, Nayla; Tauk, Alain; Mouhanna-Fattal, Carole; Bouserhal, Joseph P

2017-12-01

The main aim of this study was to describe the contribution of the maxilla and the mandible to the establishment of a Class II skeletal malocclusion in an adult Lebanese population. Secondary aims were to detect the presence of sex-based dimorphism and to study the influence of the vertical dimension on the Class II skeletal pattern. A sample of 90 adults in skeletal Class II was recruited and equally distributed according to sex and vertical typology. The study describes the skeletal and dentoalveolar cephalometric characteristics of the Class II sample, essentially according to Coben's cephalometric analysis. The total effective depth of the cranial base and the anterior cranial base angle (SN-BaH) were both greater in the Class II sample. In females, the effective depth of the maxilla (Ptm-A) was larger than normal while SNB was smaller. The parameters describing the size and shape of the body of the mandible were significantly different from those of normal subjects. The upper incisors were in a retrusive position, while the axis of the lower incisors was located normally. The mandibular molars had a more distal sagittal position. Hyperdivergent subjects had more significant posterior alveolar growth, a more retrusive mandibular position and smaller mandibular dimensions than the other two vertical sub-groups. The cranial base contributes to the establishment of a Class II malocclusion, and mandibular retrusion cannot be considered as a characteristic shared by all skeletal Class II subjects. Lessening of the absolute length of the mandibular body is the second most frequent etiological factor noted in the Class II sample studied. Most individuals in skeletal Class II have an associated dental Class II malocclusion, and the vertical dimension has an influence on the Class II skeletal pattern. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanoma.

PubMed

Dankner, Matthew; Lajoie, Mathieu; Moldoveanu, Dan; Nguyen, Tan-Trieu; Savage, Paul; Rajkumar, Shivshankari; Huang, Xiu; Lvova, Maria; Protopopov, Alexei; Vuzman, Dana; Hogg, David; Park, Morag; Guiot, Marie-Christine; Petrecca, Kevin; Mihalcioiu, Catalin; Watson, Ian R; Siegel, Peter M; Rose, April A N

2018-06-14

Dual MAPK pathway inhibition (dMAPKi) with BRAF and MEK inhibitors improves survival in BRAF V600E/K mutant melanoma, but the efficacy of dMAPKi in non-V600 BRAF mutant tumors is poorly understood. We sought to characterize the responsiveness of class II (enhanced kinase activity, dimerization dependent) BRAF mutant melanoma to dMAPKi. Tumors from patients with BRAF WT, V600E (class I) and L597S (class II) metastatic melanoma were used to generate patient-derived-xenografts (PDX). We assembled a panel of melanoma cell lines with class IIa (activation segment) or IIb (p-loop) mutations and compared these to wild-type or V600E/K BRAF mutant cells. Cell lines and PDXs were treated with BRAFi (vemurafenib, dabrafenib, encorafenib, LY3009120), MEKi (cobimetinib, trametinib, binimetinib) or the combination. We identified two patients with BRAF L597S metastatic melanoma who were treated with dMAPKi. BRAFi impaired MAPK signalling and cell growth in class I and II BRAF mutant cells. dMAPKi was more effective than either single MAPKi at inhibiting cell growth in all class II BRAF mutant cells tested. dMAPKi caused tumor regression in two melanoma PDXs with class II BRAF mutations, and prolonged survival of mice with class II BRAF mutant melanoma brain metastases. Two patients with BRAF L597S mutant melanoma clinically responded to dMAPKi. Class II BRAF mutant melanoma are growth inhibited by dMAPKi. Responses to dMAPKi have been observed in two patients with class II BRAF mutant melanoma. This data provides rationale for clinical investigation of dMAPKi in patients with class II BRAF mutant metastatic melanoma. Copyright ©2018, American Association for Cancer Research.

Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro

PubMed Central

2014-01-01

Introduction The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n = 10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow cytometry. Tri-lineage differentiation assays were performed to confirm MSC multipotency. Recombinant equine IFN-γ was used to stimulate MHC class II negative MSCs in culture, after which expression of MHC class II was re-examined. To assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs. Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE attenuation by using flow cytometry and reported as the number of cells in the proliferating T-cell gate. Results MSCs varied widely in MHC class II expression despite being homogenous in terms of “stemness” marker expression and ability to undergo trilineage differentiation. Stimulation of MHC class II negative MSCs with IFN-γ resulted in markedly increased expression of MHC class II. MLR results revealed that MHC-mismatched MHC class II-positive MSCs caused significantly increased responder T-cell proliferation compared with MHC-mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of the positive control of MHC-mismatched leukocytes. Conclusions The results of this study suggest that MSCs should be confirmed as MHC class II negative before allogeneic application. Additionally, it must be considered that even MHC class II-negative MSCs could upregulate MHC class II expression if implanted into an area of active inflammation, as demonstrated with in vitro stimulation with IFN-γ. PMID:24461709

Creation of a type IIS restriction endonuclease with a long recognition sequence

PubMed Central

Lippow, Shaun M.; Aha, Patti M.; Parker, Matthew H.; Blake, William J.; Baynes, Brian M.; Lipovšek, Daša

2009-01-01

Type IIS restriction endonucleases cleave DNA outside their recognition sequences, and are therefore particularly useful in the assembly of DNA from smaller fragments. A limitation of type IIS restriction endonucleases in assembly of long DNA sequences is the relative abundance of their target sites. To facilitate ligation-based assembly of extremely long pieces of DNA, we have engineered a new type IIS restriction endonuclease that combines the specificity of the homing endonuclease I-SceI with the type IIS cleavage pattern of FokI. We linked a non-cleaving mutant of I-SceI, which conveys to the chimeric enzyme its specificity for an 18-bp DNA sequence, to the catalytic domain of FokI, which cuts DNA at a defined site outside the target site. Whereas previously described chimeric endonucleases do not produce type IIS-like precise DNA overhangs suitable for ligation, our chimeric endonuclease cleaves double-stranded DNA exactly 2 and 6 nt from the target site to generate homogeneous, 5′, four-base overhangs, which can be ligated with 90% fidelity. We anticipate that these enzymes will be particularly useful in manipulation of DNA fragments larger than a thousand bases, which are very likely to contain target sites for all natural type IIS restriction endonucleases. PMID:19304757

Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase.

PubMed

Klyushnenkova, Elena N; Kouiavskaia, Diana V; Kodak, James A; Vandenbark, Arthur A; Alexander, Richard B

2007-07-01

The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

49 CFR 1150.35 - Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Procedures and relevant dates-transactions that involve creation of Class I or Class II carriers. 1150.35 Section 1150.35 Transportation Other Regulations.... 10901 § 1150.35 Procedures and relevant dates—transactions that involve creation of Class I or Class II...

Prescription of land-surface boundary conditions in GISS GCM 2: A simple method based on high-resolution vegetation data bases

NASA Technical Reports Server (NTRS)

Matthews, E.

1984-01-01

A simple method was developed for improved prescription of seasonal surface characteristics and parameterization of land-surface processes in climate models. This method, developed for the Goddard Institute for Space Studies General Circulation Model II (GISS GCM II), maintains the spatial variability of fine-resolution land-cover data while restricting to 8 the number of vegetation types handled in the model. This was achieved by: redefining the large number of vegetation classes in the 1 deg x 1 deg resolution Matthews (1983) vegetation data base as percentages of 8 simple types; deriving roughness length, field capacity, masking depth and seasonal, spectral reflectivity for the 8 types; and aggregating these surface features from the 1 deg x 1 deg resolution to coarser model resolutions, e.g., 8 deg latitude x 10 deg longitude or 4 deg latitude x 5 deg longitude.

In vitro Peptide Immunization ofTargetTax Protein HumanT-Cell Leukemia Virus Type 1 – Specific CD4+ Helper T Lymphocytes

PubMed Central

Kobayashi, Hiroya; Ngato, Toshihiro; Sato, Keisuke; Aoki, Naoko; Kimura, Shoji; Tanaka, Yuetsu; Aizawa, Hitoshi; Tateno, Masatoshi; Celis, Esteban

2006-01-01

Purpose Adult T-cell leukemia/lymphoma induced by human T-cell leukemia virus type 1 (HTLV-1) is usually a fatal lymphoproliferative malignant disease. HTLV-1 Tax protein plays a critical role in HTLV-1-associated leukemogenesis and is an attractive target for vaccine development. Although HTLV-1Tax is the most dominant antigen for HTLV-1-specific CD8+ CTLs in HTLV-1-infected individuals, few epitopes recognized by CD4+ helper T lymphocytes in HTLV-1Tax protein have been described.The aim of the present study was to study T-helper-cell responses to HTLV-1 Tax and to identify naturally processed MHC class II – restricted epitopes that could be used for vaccine development. Experimental Design An MHC class II binding peptide algorithm was used to predict potential T-helper cell epitope peptides from HTLV-1 Tax. We assessed the ability of the corresponding peptides to elicit helper T-cell responses by in vitro vaccination of purified CD4+ T lymphocytes. Results Peptides Tax191–205 and Tax305–319 were effective in inducingT-helper-cell responses. Although Tax191–205 was restricted by the HLA-DR1 and DR9 alleles, responses to Tax305–319 were restricted by either DR15 or DQ9. Both these epitopes were found to be naturally processed by HTLV-1+ T-cell lymphoma cells and by autologous antigen-presenting cells that were pulsed with HTLV-1Tax+ tumor lysates. Notably, the two newly identified helper T-cell epitopes are found to lie proximal to known CTL epitopes, which will facilitate the development of prophylactic peptide – based vaccine capable of inducing simultaneous CTL andT-helper responses. Conclusion Our data suggest that HTLV-1 Tax protein could serve as tumor-associated antigen for CD4+ helper T cells and that the present epitopes might be used for T-cell-based immunotherapy against tumors expressing HTLV-1. PMID:16778109

Purification of antilisterial bacteriocins.

PubMed

Berjeaud, Jean-Marc; Cenatiempo, Yves

2004-01-01

In recent years, numerous contamination outbreaks, involving various pathogens (i.e., Listeria and Salmonella), have increased concern over food preservation. Research efforts have focused on the discovery of new molecules targeting such foodborne pathogens and therefore able to inhibit and or kill them. Lactic acid bacteria (LAB) extensively used in fermented foods for thousands of years not only improve their flavor and texture but also inhibit pathogenic and spoilage microorganisms. LAB inhibitory activity is primarily owing to pH decrease and competition for substrates. Antagonistic activity of LAB also depends on secreted antimicrobial compounds with a poor selectivity, such as metabolic compounds (i.e., hydrogen peroxide, acetoin, and others) or more specific ones like bacteriocins. The latter are proteinaceous compounds, ribosomally synthesized and subsequently secreted by Gram-positive as well as Gram-negative bacteria. Their antimicrobial activity is generally restricted to strains phylogenetically related to the producers.A classification of bacteriocins produced by LAB was first proposed by Klaenhammer in 1993 and was modified by Nes et al. in 1996; class I and class II bacteriocins are the most abundant and thoroughly studied. Bacteriocins from both classes exhibit antilisterial activity. Class I bacteriocins, namely, lantibiotics, have been widely studied, and among them, nisin is used in many countries as a preservative in food products. These bacteriocins are characterized by the presence, in their primary structure, of post-translationally modified amino acid residues (i.e., lanthionine and methylanthionine) that are formed. Class II bacteriocins, containing three subclasses, consist of small peptides that do not bear any modified amino acid residue. The most studied subclass corresponds to class IIa, also termed anti-Listeria bacteriocins. These peptides share strong structural homologies in their N-terminal domain, with the presence of one disulfide bond and a net positive charge. Their C-terminal domain is more variable but appears quite hydrophobic. Moreover, some of these bacteriocins, namely, sakacin G, pediocin PA-1, enterocin A, coagulin, and divercin V41, are characterized by the presence of a second disulfide bond in the C-terminal region.

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

49 CFR 572.127 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Forces—Class 1000; (ii) Moments—Class 600; (iii) Pendulum acceleration—Class 180; (iv) Rotation—Class 60 (if used). (3) Thorax: (i) Rib acceleration—Class 1000; (ii) Spine and pendulum accelerations—Class...

Postoperative surgical complications of lymphadenohysterocolpectomy

PubMed Central

Marin, F; Pleşca, M; Bordea, CI; Voinea, SC; Burlănescu, I; Ichim, E; Jianu, CG; Nicolăescu, RR; Teodosie, MP; Maher, K; Blidaru, A

2014-01-01

Rationale The current standard surgical treatment for the cervix and uterine cancer is the radical hysterectomy (lymphadenohysterocolpectomy). This has the risk of intraoperative accidents and postoperative associated morbidity. Objective The purpose of this article is the evaluation and quantification of the associated complications in comparison to the postoperative morbidity which resulted after different types of radical hysterectomy. Methods and results Patients were divided according to the type of surgery performed as follows: for cervical cancer – group A- 37 classic radical hysterectomies Class III Piver - Rutledge -Smith ( PRS ), group B -208 modified radical hysterectomies Class II PRS and for uterine cancer- group C -79 extended hysterectomies with pelvic lymphadenectomy from which 17 patients with paraaortic lymphnode biopsy . All patients performed preoperative radiotherapy and 88 of them associated radiosensitization. Discussion Early complications were intra-abdominal bleeding ( 2.7% Class III PRS vs 0.48% Class II PRS), supra-aponeurotic hematoma ( 5.4% III vs 2.4% II) , dynamic ileus (2.7% III vs 0.96% II) and uro - genital fistulas (5.4% III vs 0.96% II).The late complications were the bladder dysfunction (21.6% III vs 16.35% II) , lower limb lymphedema (13.5% III vs 11.5% II), urethral strictures (10.8% III vs 4.8% II) , incisional hernias ( 8.1% III vs 7.2% II), persistent pelvic pain (18.91% III vs 7.7% II), bowel obstruction (5.4% III vs 1.4% II) and deterioration of sexual function (83.3% III vs 53.8% II). PRS class II radical hysterectomy is associated with fewer complications than PRS class III radical hysterectomy , except for the complications of lymphadenectomy . A new method that might reduce these complications is a selective lymphadenectomy represented by sentinel node biopsy . In conclusion PRS class II radical hysterectomy associated with neoadjuvant radiotherapy is a therapeutic option for the incipient stages of cervical cancer. Abbreviations: PRS- Piver Rutledge-Smith, II- class II, III- class III PMID:24653760

An amino acid sequence coded by the exon 2 of the BoLA DRB3 gene associated with a BoLA class I specificity constitutes a likely genetic marker of resistance to dermatophilosis in Brahman zebu cattle of Martinique (FWI).

PubMed

Maillard, J C; Martinez, D; Bensaid, A

1996-07-23

One hundred and twenty-seven Brahman cattle from several locations in Martinique (FWI), reared under different environmental conditions, were followed over three years and checked for clinical signs of dermatophilosis. To confirm that these animals had been in contact with the pathogen Dermatophilus congolensis, their sera were tested by ELISA. On the basis of this epidemiological study, 12 animals were classified as resistant (seropositive without clinical signs), belonging to herds in which the prevalence of the disease ranged from 25 to nearly 98%. Eighteen animals classified as highly susceptible displayed severe characteristic skin lesions. These 30 selected animals were typed for class I antigens of the major histocompatibility complex (MHC). MHC class II genes were analyzed using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques, on the exon 2 of the bovine leucocyte antigen (BoLA) DRB3 gene. Several alleles were found, according to patterns provided by the restriction enzymes used: Fnu 4HI, Dpn II, Hae III, and Rsa I. A particular sequence "EIAY" at amino acid positions 66/67/74/78 located in the antigen recognition sites (ARS) was found in the 12 animals classified as resistant, and 10 of them displayed also class I BoLA-A8 specificity. On the other hand, only 3 out of the 18 susceptible animals showed simultaneously the BoLA-DRB3 "EIAY" sequence and BoLA-A8 specificity. Interestingly, a serine residue at position 30 of the ARS was found in 8 of the susceptible animals and was completely absent from all resistant animals. Furthermore, in a same animal, the serine at position 30 and the EIAY sequence were never found simultaneously on the same haplotype. These results show a strong correlation between the resistant character to dermatophilosis and the association of MHC haplotypes: the BoLA-A8 specificity and the BoLA-DRB3 "EIAY" sequence at ARS positions 66/67/74/78 with the lack of serine in position 30. To confirm these results, family segregation studies are in progress and some interesting observations have been obtained.

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

49 CFR 572.146 - Test conditions and instrumentation.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Head acceleration—Class 1000 (2) Neck (i) Force—Class 1000 (ii) Moments—Class 600 (iii) Pendulum... acceleration—Class 1000 (ii) Spine and pendulum accelerations—Class 180 (iii) Sternum deflection—Class 600 (iv...

HLA-F polymorphisms in a Euro-Brazilian population from Southern Brazil.

PubMed

Manvailer, L F S; Wowk, P F; Mattar, S B; da Siva, J S; da Graça Bicalho, M; Roxo, V M M S

2014-12-01

HLA-F is a non-classical major histocompatibility complex (MHC) gene. It codes class Ib MHC molecules with restricted distribution and less nucleotide variations than MHC class Ia genes. Of the 22 alleles registered on the IMGT database only four alleles encode for proteins that differ in their primary structure. To estimate genotype and allele frequencies, this study targeted on known protein coding regions of the HLA-F gene. Genotyping was performed by Sequence Base Typing (SBT). The sample was composed by 199-unrelated bone marrow donors from the Brazilian Bone Marrow Donor Registry (REDOME), Euro-Brazilians, from Southern Brazil. About 1673 bp were analyzed. The most frequent allele was HLA-F*01:01 (87.19%), followed by HLA-F*01:03 (12.31%), HLA-F*01:02 (0.25%) and HLA-F*01:04 (0.25%). Significant linkage disequilibrium (LD) was verified between HLA-F and HLA classes I and II alleles. This is the first study regarding HLA-F polymorphisms in a Euro-Brazilian population contributing to the Southern Brazilian genetic characterization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dental cavity liners for Class I and Class II resin-based composite restorations.

PubMed

Schenkel, Andrew B; Peltz, Ivy; Veitz-Keenan, Analia

2016-10-25

Resin-based composite (RBC) is currently accepted as a viable material for the restoration of caries for posterior permanent teeth requiring surgical treatment. Despite the fact that the thermal conductivity of the RBC restorative material closely approximates that of natural tooth structure, postoperative hypersensitivity is sometimes still an issue. Dental cavity liners have historically been used to protect the pulp from the toxic effects of some dental restorative materials and to prevent the pain of thermal conductivity by placing an insulating layer between restorative material and the remaining tooth structure. The objective of this review was to assess the effects of using dental cavity liners in the placement of Class I and Class II resin-based composite posterior restorations in permanent teeth in children and adults. Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 25 May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 4) in the Cochrane Library (searched 25 May 2016), MEDLINE Ovid (1946 to 25 May 2016), Embase Ovid (1980 to 25 May 2016) and LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 25 May 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We included randomized controlled trials assessing the effects of the use of liners under Class I and Class II posterior resin-based composite restorations in permanent teeth (in both adults and children). We included both parallel and split-mouth designs. We utilized standard methodological procedures prescribed by Cochrane for data collection and analysis. Two review authors screened the search results and assessed the eligibility of studies for inclusion against the review inclusion criteria. We conducted risk of bias assessments and data extraction independently and in duplicate. Where information was unclear we contacted study authors for clarification. Eight studies, recruiting over 700 participants, compared the use of dental cavity liners to no liners for Class I and Class II resin-based composite restorations.Seven studies evaluated postoperative hypersensitivity measured by various methods. All studies were at unclear or high risk of bias. There was inconsistent evidence regarding postoperative hypersensitivity (either measured using cold response or patient-reported), with a benefit shown at some, but not all, time points (low-quality evidence).Four trials measured restoration longevity. Two of the studies were judged to be at high risk and two at unclear risk of bias. No difference in restoration failure rates were shown at one year follow-up, with no failures reported in either group for three of the four studies; the fourth study had a risk ratio (RR) 1.00 (95% confidence interval (CI) 0.07 to 15.00) (low-quality evidence). Three studies evaluated restoration longevity at two years follow-up and, again, no failures were shown in either group.No adverse events were reported in any of the included studies. There is inconsistent, low-quality evidence regarding the difference in postoperative hypersensitivity subsequent to placing a dental cavity liner under Class I and Class II posterior resin-based composite restorations in permanent posterior teeth in adults or children 15 years or older. Furthermore, no evidence was found to demonstrate a difference in the longevity of restorations placed with or without dental cavity liners.

Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample.

PubMed

Florián-Vargas, Karla; Honores, Marcos J Carruitero; Bernabé, Eduardo; Flores-Mir, Carlos

2016-01-01

To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively) from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES) and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA) was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 ± 3.96, 21.96 ± 3.27 and 21.26 ± 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted.

Occlusal status in Asian male adults: prevalence and ethnic variation.

PubMed

Soh, Jen; Sandham, Andrew; Chan, Yiong Huak

2005-09-01

The purpose of this study was to determine the occlusal status in young Asian male adults of three ethnic groups. Study models of a sample of male army recruits (N = 339, age 17-22 years) with no history of orthodontic treatment were assessed. The ethnic proportions of the sample were Chinese 76.1% (n = 258), Malay 17.7% (n = 60), and Indian 6.2% (n = 21). British Standard Institute (BSI) and Angle's classification were used to determine incisor and molar relationships, respectively. Chi-square test or Fisher's Exact test was performed to compare the occlusal traits between ethnic groups. The distribution of incisor relationships of the total sample consisted of Class I = 48.1%, Class II/1 = 26.3%, Class II/2 = 3.2%, and Class III = 22.4%. Right Angle's molar relationships were 49.9%, 24.5%, and 24.2% whereas left Angle's molar relationships were 53.1%, 25.1%, and 21.2% for Class I, II, and III, respectively. Comparison between ethnic groups found that Indian subjects were more likely to have Class II/1 malocclusions and clinically missing permanent teeth (P < .05). The study found that the overall prevalence of malocclusion (BSI) was Class I, Class II/1, Class III, and Class II/2 in descending order of proportions. Angle's Class I molar was most prevalent followed by Class II and Class III relations. A significant difference in occlusal status between the ethnic groups was found regarding incisor relationship and missing permanent teeth (P < .05).

Sequence, distribution and chromosomal context of class I and class II pilin genes of Neisseria meningitidis identified in whole genome sequences

PubMed Central

2014-01-01

Background Neisseria meningitidis expresses type four pili (Tfp) which are important for colonisation and virulence. Tfp have been considered as one of the most variable structures on the bacterial surface due to high frequency gene conversion, resulting in amino acid sequence variation of the major pilin subunit (PilE). Meningococci express either a class I or a class II pilE gene and recent work has indicated that class II pilins do not undergo antigenic variation, as class II pilE genes encode conserved pilin subunits. The purpose of this work was to use whole genome sequences to further investigate the frequency and variability of the class II pilE genes in meningococcal isolate collections. Results We analysed over 600 publically available whole genome sequences of N. meningitidis isolates to determine the sequence and genomic organization of pilE. We confirmed that meningococcal strains belonging to a limited number of clonal complexes (ccs, namely cc1, cc5, cc8, cc11 and cc174) harbour a class II pilE gene which is conserved in terms of sequence and chromosomal context. We also identified pilS cassettes in all isolates with class II pilE, however, our analysis indicates that these do not serve as donor sequences for pilE/pilS recombination. Furthermore, our work reveals that the class II pilE locus lacks the DNA sequence motifs that enable (G4) or enhance (Sma/Cla repeat) pilin antigenic variation. Finally, through analysis of pilin genes in commensal Neisseria species we found that meningococcal class II pilE genes are closely related to pilE from Neisseria lactamica and Neisseria polysaccharea, suggesting horizontal transfer among these species. Conclusions Class II pilins can be defined by their amino acid sequence and genomic context and are present in meningococcal isolates which have persisted and spread globally. The absence of G4 and Sma/Cla sequences adjacent to the class II pilE genes is consistent with the lack of pilin subunit variation in these isolates, although horizontal transfer may generate class II pilin diversity. This study supports the suggestion that high frequency antigenic variation of pilin is not universal in pathogenic Neisseria. PMID:24690385

Comparison of second molar eruption patterns in patients with skeletal Class II and skeletal Class I malocclusions.

PubMed

Brin, Ilana; Camasuvi, Semin; Dali, Nasser; Aizenbud, Dror

2006-12-01

The eruptive positions of the second molars in Class I and Class II malocclusions were studied. Pretreatment records of 221 patients with a mean age of 11.3 years were evaluated. About 19% of them had skeletal Class I, 31% had skeletal maxillary Class II, and 50% had skeletal mandibular Class II malocclusions. The mean values of the dental and chronologic ages of the subjects were similar. The eruptive positions in relation to a reference line, the developmental stages of the patients' second molars and dental ages were recorded from the panoramic roentgenograms. The distribution of the various developmental stages in each malocclusion group was similar, and no association between skeletal malocclusion and dental developmental stage of the second molars was encountered. The eruptive position of the maxillary second molars was more occlusal only in the oldest maxillary Class II group, above 12 years of age (P = .02). These results support, in part, previous reports suggesting that the maxillary second molars may erupt earlier in patients with skeletal maxillary Class II malocclusions.

Inhibitory effects of thymus-independent type 2 antigens on MHC class II-restricted antigen presentation: comparative analysis of carbohydrate structures and the antigen presenting cell.

PubMed

González-Fernández, M; Carrasco-Marín, E; Alvarez-Domínguez, C; Outschoorn, I M; Leyva-Cobián, F

1997-02-25

The role of thymus-independent type 2 (TI-2) antigens (polysaccharides) on the MHC-II-restricted processing of protein antigens was studied in vitro. In general, antigen presentation is inhibited when both peritoneal and splenic macrophages (M phi) as well as Küpffer cells (KC) are preincubated with acidic polysaccharides or branched dextrans. However, the inhibitory effect of neutral polysaccharides was minimal when KC were used as antigen presenting cells (APC). Morphological evaluation of the uptake of fluoresceinated polysaccharides clearly correlates with this selective and differential interference. Polysaccharides do not block MHC-I-restricted antigen presentation. Some chemical characteristics shared by different saccharides seem to be specially related to their potential inhibitory abilities: (i) those where two anomeric carbon atoms of two interlinked sugars and (ii) those containing several sulfate groups per disaccharide repeating unit. No polysaccharide being inhibitory in M phi abrogated antigen processing in other APC: lipopolysaccharide-activated B cells, B lymphoma cells, or dendritic cells (DC). Using radiolabeled polysaccharides it was observed that DC and B cells incorporated less radioactivity as a function of time than M phi. Morphological evaluation of these different APC incubated for extended periods of time with inhibitory concentrations of polysaccharides revealed intense cytoplasmic vacuolization in M phi but not in B cells or DC. The large majority of M phi lysosomes containing polysaccharides fail to fuse with incoming endocytic vesicles and delivery of fluid-phase tracers was reduced, suggesting that indigestible carbohydrates reduced the fusion of these loaded lysosomes with endosomes containing recently internalized tracers. It is suggested that the main causes of this antigen presentation blockade are (i) the chemical characteristics of certain carbohydrates and whether the specific enzymatic machinery for their intracellular degradation exists; and (ii) the different phagocytic abilities of distinct APC populations, fluid-phase pinocytosis and receptor-mediated saccharide uptake, and existence of a differential antigen-processing pathway in M phi and DC or B cells, which could be based on a polysaccharide-inhibited step present in M phi but unaffected or irrelevant in both B cells and DC.

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Nonessential Class II products and... PROGRAMS (CONTINUED) PROTECTION OF STRATOSPHERIC OZONE Ban on Nonessential Products Containing Class I Substances and Ban on Nonessential Products Containing or Manufactured With Class II Substances § 82.70...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

14 CFR 61.5 - Certificates and ratings issued under this part.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-control aircraft. (2) Airplane class ratings— (i) Single-engine land. (ii) Multiengine land. (iii) Single-engine sea. (iv) Multiengine sea. (3) Rotorcraft class ratings— (i) Helicopter. (ii) Gyroplane. (4) Lighter-than-air class ratings— (i) Airship. (ii) Balloon. (5) Weight-shift-control aircraft class ratings...

Molecular characterization of two types of resistance in sunflower to Plasmopara halstedii, the causal agent of downy mildew.

PubMed

Radwan, Osman; Bouzidi, Mohamed Fouad; Mouzeyar, Said

2011-08-01

Depending on host-pathotype combination, two types of sunflower-Plasmopara halstedii incompatibility reactions have previously been identified. Type I resistance can restrict the growth of the pathogen in the basal region of the hypocotyls, whereas type II cannot, thus allowing the pathogen to reach the cotyledons. In type II resistance, a large portion of the hypocotyls is invaded by the pathogen and, subsequently, a hypersensitive reaction (HR) is activated over a long portion of the hypocotyls. Thus, the HR in type II resistance coincides with a higher induction of hsr203j sunflower homologue in comparison with type I resistance, where the HR is activated only in the basal part of hypocotyls. Although the pathogen was not detected in cotyledons of type I resistant plants, semiquantitative polymerase chain reaction confirmed the early abundant growth of the pathogen in cotyledons of susceptible plants by 6 days postinfection (dpi). This was in contrast to scarce growth of the pathogen in cotyledons of type II-resistant plants at a later time point (12 dpi). This suggests that pathogen growth differs according to the host-pathogen combination. To get more information about sunflower downy mildew resistance genes, the full-length cDNAs of RGC151 and RGC203, which segregated with the PlARG gene (resistance type I) and Pl14 gene (resistance type II), were cloned and sequenced. Sequence analyses revealed that RGC151 belongs to the Toll/interleukin-1 receptor (TIR) nucleotide-binding site leucine-rich repeat (NBS-LRR) class whereas RGC203 belongs to class coiled-coil (CC)-NBS-LRR. This study suggests that type II resistance may be controlled by CC-NBS-LRR gene transcripts which are enhanced upon infection by P. halstedii, rather than by the TIR-NBS-LRR genes that might control type I resistance.

HLA Class II Defects in Burkitt Lymphoma: Bryostatin-1-Induced 17 kDa Protein Restores CD4+ T-Cell Recognition

PubMed Central

Hossain, Azim; God, Jason M.; Radwan, Faisal F. Y.; Amria, Shereen; Zhao, Dan; Bethard, Jennifer R.; Haque, Azizul

2011-01-01

While the defects in HLA class I-mediated Ag presentation by Burkitt lymphoma (BL) have been well documented, CD4+ T-cells are also poorly stimulated by HLA class II Ag presentation, and the reasons underlying this defect(s) have not yet been fully resolved. Here, we show that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. The observed defect was not associated with low levels of BL-expressed costimulatory molecules, as addition of external co-stimulation failed to result in BL-mediated CD4+ T-cell activation. We further demonstrate that BL cells express the components of the class II pathway, and the defect was not caused by faulty Ag/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Treatment of BL with broystatin-1, a potent modulator of protein kinase C, led to significant improvement of functional class II Ag presentation in BL. The restoration of immune recognition appeared to be linked with an increased expression of a 17 kDa peptidylprolyl-like protein. These results demonstrate the presence of a specific defect in HLA class II-mediated Ag presentation in BL and reveal that treatment with bryostatin-1 could lead to enhanced immunogenicity. PMID:22162713

Refinement of the MHC Risk Map in a Scandinavian Primary Sclerosing Cholangitis Population

PubMed Central

Næss, Sigrid; Lie, Benedicte A.; Melum, Espen; Olsson, Marita; Hov, Johannes R.; Croucher, Peter J. P.; Hampe, Jochen; Thorsby, Erik; Bergquist, Annika; Traherne, James A.; Schrumpf, Erik; Boberg, Kirsten Muri; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H.

2014-01-01

Background Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel. Methodology/Principal Findings A total of 365 PSC cases and 368 healthy controls of Scandinavian ancestry were included in the study. We incorporated data from HLA typing (HLA-A, -B, -C, -DRB3, -DRB1, -DQB1) and single nucleotide polymorphisms across the MHC (n = 18,644; genotyped and imputed) alongside previously suggested PSC risk determinants in the MHC, i.e. amino acid variation of DRβ, a MICA microsatellite polymorphism and HLA-C and HLA-B according to their ligand properties for killer immunoglobulin-like receptors. Breakdowns of the association signal by unconditional and conditional logistic regression analyses demarcated multiple PSC associated MHC haplotypes, and for eight of these classical HLA class I and II alleles represented the strongest association. A novel independent risk locus was detected near NOTCH4 in the HLA class III region, tagged by rs116212904 (odds ratio [95% confidence interval] = 2.32 [1.80, 3.00], P = 1.35×10−11). Conclusions/Significance Our study shows that classical HLA class I and II alleles, predominantly at HLA-B and HLA-DRB1, are the main risk factors for PSC in the MHC. In addition, the present assessments demonstrated for the first time an association near NOTCH4 in the HLA class III region. PMID:25521205

Genetic susceptibility to endomyocardial fibrosis

PubMed Central

Beaton, Andrea; Sable, Craig; Brown, Juliette; Hoffman, Joshua; Mungoma, Michael; Mondo, Charles; Cereb, Nezith; Brown, Colin; Summar, Marshall; Freers, Jurgen; Ferreira, Maria Beatriz; Yacoub, Magdi; Mocumbi, Ana Olga

2014-01-01

Background: Endomyocardial fibrosis (EMF) is the most common form of restrictive cardiomyopathy worldwide. It has been linked to poverty and various environmental factors, but—for unknown reasons—only some people who live in similar conditions develop the disease. EMF cases cluster within both families and ethnic groups, suggesting a role for a genetic factor in host susceptibility. The human leukocyte antigen (HLA) system is associated with predisposition to various diseases. This two-center study was designed to investigate variation in the HLA system between EMF patients and unaffected controls. We provide the first genetic investigation of patients with EMF, as well as a comprehensive review of the literature. Methods: HLA class I (HLA-A, -B, -C) and class II (DRB1, DQB1) types were determined in 71 patients with severe EMF and 137 controls from Uganda and Mozambique. Chi Square analysis was used to identify any significant difference in frequency of class I and class II HLA types between cases and controls. Results: Compared to ethnically matched controls, HLA-B*58 occurred more frequently in Mozambique patients with EMF and HLA-A*02:02 occurred more frequently in Ugandan patients with EMF. Conclusions: Ample subjective evidence in the historical literature suggests the importance of a genetically susceptible host in EMF development. In this first formal genetic study, we found HLA alleles associated with cases of EMF in two populations from sub-Saharan Africa, with EMF patients being more likely than controls to have the HLA-B*58 allele in Mozambique (p-0.03) and the HLA-A*02:02 in Uganda (p = 0.005). Further investigations are needed to more fully understand the role of genetics in EMF development. PMID:25780800

38 CFR 36.4362 - Rights and restrictions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... parking areas or facilities. (ii) Any contract or lease, including franchises and licenses, to which a declarant is a party. (iii) The requirements of paragraphs (a)(2)(i) and (ii) of this section do not apply... restrictions are acceptable: (i) A requirement that leases have a minimum initial term of up to 1 year; or (ii...

Mechanisms regulating enhanced HLA class II-mediated CD4+ T cell recognition of human B-cell lymphoma by resveratrol

PubMed Central

RADWAN, FAISAL F. Y.; ZHANG, LIXIA; HOSSAIN, AZIM; DOONAN, BENTLY P.; GOD, JASON; HAQUE, AZIZUL

2015-01-01

Malignant B-cells express measurable levels of HLA class II proteins, but often escape immune recognition by CD4+ T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an upregulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4+ T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through upregulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma. PMID:21854084

Shark class II invariant chain reveals ancient conserved relationships with cathepsins and MHC class II.

PubMed

Criscitiello, Michael F; Ohta, Yuko; Graham, Matthew D; Eubanks, Jeannine O; Chen, Patricia L; Flajnik, Martin F

2012-03-01

The invariant chain (Ii) is the critical third chain required for the MHC class II heterodimer to be properly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells. Here, we report the isolation of the nurse shark Ii gene, and the comparative analysis of Ii splice variants, expression, genomic organization, predicted structure, and function throughout vertebrate evolution. Alternative splicing to yield Ii with and without the putative protease-protective, thyroglobulin-like domain is as ancient as the MHC-based adaptive immune system, as our analyses in shark and lizard further show conservation of this mechanism in all vertebrate classes except bony fish. Remarkable coordinate expression of Ii and class II was found in shark tissues. Conserved Ii residues and cathepsin L orthologs suggest their long co-evolution in the antigen presentation pathway, and genomic analyses suggest 450 million years of conserved Ii exon/intron structure. Other than an extended linker preceding the thyroglobulin-like domain in cartilaginous fish, the Ii gene and protein are predicted to have largely similar physiology from shark to man. Duplicated Ii genes found only in teleosts appear to have become sub-functionalized, as one form is predicted to play the same role as that mediated by Ii mRNA alternative splicing in all other vertebrate classes. No Ii homologs or potential ancestors of any of the functional Ii domains were found in the jawless fish or lower chordates. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acculturation levels and personalizing orthognathic surgery for the Asian American patient.

PubMed

Sy, A A; Kim, W S; Chen, J; Shen, Y; Tao, C; Lee, J S

2016-10-01

This study was performed to investigate whether the level of acculturation among Asians living in the USA plays a significant role in their opinion of facial profiles. One hundred and ninety-eight Asian American subjects were asked to complete a pre-validated survey to measure their level of acculturation and to evaluate four sets of pictures that displayed a class II male, class II female, class III male, and class III female. Each set consisted of three lateral profile pictures: an initial unaltered photo, a picture simulating a flatter profile (orthodontic camouflage in class II; mandibular setback in class III), and a picture simulating a fuller profile (mandibular advancement in class II; maxillary advancement in class III). For the class II male, subjects who were more acculturated indicated that a flatter profile (orthodontic camouflage) was less attractive. For the class II female, higher acculturated subjects chose expansive treatment (mandibular advancement) as more aesthetic compared to the less acculturated subjects. Each of these scenarios had statistically significant odds ratios. In general, highly acculturated subjects preferred a fuller facial profile, while low acculturated subjects preferred a flatter facial profile appearance, except for the class III female profile, which did not follow this trend. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

SO(N) restricted Schur polynomials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kemp, Garreth, E-mail: garreth.kemp@students.wits.ac.za

2015-02-15

We focus on the 1/4-BPS sector of free super Yang-Mills theory with an SO(N) gauge group. This theory has an AdS/CFT (an equivalence between a conformal field theory in d-1 dimensions and type II string theory defined on an AdS space in d-dimensions) dual in the form of type IIB string theory with AdS{sub 5}×RP{sup 5} geometry. With the aim of studying excited giant graviton dynamics, we construct an orthogonal basis for this sector of the gauge theory in this work. First, we demonstrate that the counting of states, as given by the partition function, and the counting of restrictedmore » Schur polynomials match by restricting to a particular class of Young diagram labels. We then give an explicit construction of these gauge invariant operators and evaluate their two-point function exactly. This paves the way to studying the spectral problem of these operators and their D-brane duals.« less

Tanning beds: Impact on health, and recent regulations.

PubMed

Madigan, Lauren M; Lim, Henry W

2016-01-01

As the use of indoor tanning beds gained popularity in the decades after their appearance in the market in the early 1970s, concerns arose regarding their use. Clinical research has revealed an association between indoor tanning and several health risks, including the subsequent occurrence of melanoma and nonmelanoma skin cancers, the development of psychologic dependence, and a tendency toward other high-risk health behaviors. In the face of mounting evidence, legislation has been passed, which includes the restriction of access to tanning beds by minors in 42 states and the District of Columbia, and the recent reclassification by the Food and Drug Administration, which now categorizes tanning beds as class II devices and worthy of restrictions and oversight. Early evidence suggests that these labors are resulting in cultural change, although continued efforts are necessary to limit further exposure and better inform the public of the dangers associated with indoor tanning use. Copyright © 2016 Elsevier Inc. All rights reserved.

Antigen-specific and non-specific CD4{sup +} T cell recruitment and proliferation during influenza infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Timothy J.; Castrucci, Maria R.; Padrick, Ryan C.

To track epitope-specific CD4{sup +} T cells at a single-cell level during influenza infection, the MHC class II-restricted OVA{sub 323-339} epitope was engineered into the neuraminidase stalk of influenza/A/WSN, creating a surrogate viral antigen. The recombinant virus, influenza A/WSN/OVA{sub II}, replicated well, was cleared normally, and stimulated both wild-type and DO11.10 or OT-II TCR transgenic OVA-specific CD4{sup +} T cells. OVA-specific CD4 T cells proliferated during infection only when the OVA epitope was present. However, previously primed (but not naive) transgenic CD4{sup +} T cells were recruited to the infected lung both in the presence and absence of the OVA{submore » 323-339} epitope. These data show that, when primed, CD4{sup +} T cells may traffic to the lung in the absence of antigen, but do not proliferate. These results also document a useful tool for the study of CD4 T cells in influenza infection.« less

Evaluation of skeletal and dental asymmetries in Angle Class II subdivision malocclusions with cone-beam computed tomography.

PubMed

Minich, Craig M; Araújo, Eustáquio A; Behrents, Rolf G; Buschang, Peter H; Tanaka, Orlando M; Kim, Ki Beom

2013-07-01

The purpose of this study was to determine whether Angle Class II subdivision malocclusions have skeletal or dental asymmetries between the Class II and Class I sides. A sample of 54 untreated Angle Class II subdivision patients with pretreatment photos and cone-beam computed tomography (CBCT) scans was used. The photos were used to identify the Class II subdivision malocclusion and to record the amount of crowding per quadrant. Landmarks were plotted on each CBCT volume so that direct 3-dimensional measurements could be made to compare the positions and dimensions of the skeletal and dental structures on the Class II side vs the Class I side. Significant differences were found for 2 skeletal measurements: the position of the maxilla relative to the cranial base, and the mandibular dimension from the mandibular foramen to the mental foramen. Statistically significant dental differences were found for the position of the mandibular first molars and canines in relation to the maxilla and the mandible. Statistically significant differences were found for the maxillary first molars and canines in relation to the mandible. There were significant skeletal and dental differences between the Class I and Class II sides. The dental asymmetries accounted for about two thirds of the total asymmetry. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Antimalarial compounds in Phase II clinical development.

PubMed

Held, Jana; Jeyaraj, Sankarganesh; Kreidenweiss, Andrea

2015-03-01

Malaria is a major health problem in endemic countries and chemotherapy remains the most important tool in combating it. Treatment options are limited and essentially rely on a single drug class - the artemisinins. Efforts are ongoing to restrict the evolving threat of artemisinin resistance but declining sensitivity has been reported. Fueled by the ambitious aim of malaria eradication, novel antimalarial compounds, with improved properties, are now in the progressive phase of drug development. Herein, the authors describe antimalarial compounds currently in Phase II clinical development and present the results of these investigations. Thanks to recent efforts, a number of promising antimalarial compounds are now in the pipeline. First safety data have been generated for all of these candidates, although their efficacy as antimalarials is still unclear for most of them. Of particular note are KAE609, KAF156 and DSM265, which are of chemical scaffolds new to malaria chemotherapy and would truly diversify antimalarial options. Apart from SAR97276, which also has a novel chemical scaffold that has had its development stopped, all other compounds in the pipeline belong to already known substance classes, which have been chemically modified. At this moment in time, there is not one standout compound that will revolutionize malaria treatment but several compounds that will add to its control in the future.

Streptococcus suis Serotype 2 Infection Impairs Interleukin-12 Production and the MHC-II-Restricted Antigen Presentation Capacity of Dendritic Cells

PubMed Central

Letendre, Corinne; Auger, Jean-Philippe; Lemire, Paul; Galbas, Tristan; Gottschalk, Marcelo; Thibodeau, Jacques; Segura, Mariela

2018-01-01

Streptococcus suis is an important swine pathogen and emerging zoonotic agent. Encapsulated strains of S. suis modulate dendritic cell (DC) functions, leading to poorly activated CD4+ T cells. However, the antigen presentation ability of S. suis-stimulated DCs has not been investigated yet. In this work, we aimed to characterize the antigen presentation profiles of S. suis-stimulated DCs, both in vitro and in vivo. Upon direct activation in vitro, S. suis-stimulated murine bone marrow-derived DCs (bmDCs) preserved their antigen capture/processing capacities. However, they showed delayed kinetics of MHC-II expression compared to lipopolysaccharide-stimulated bmDCs. Meanwhile, splenic DCs from infected mice exhibited a compromised MHC-II expression, despite an appropriate expression of maturation markers. To identify potential interfering mechanisms, Class II Major Histocompatibility Complex Transactivator (CIITA) and membrane-associated RING-CH (MARCH)1/8 transcription were studied. S. suis-stimulated DCs maintained low levels of CIITA at early time points, both in vitro and in vivo, which could limit their ability to increase MHC-II synthesis. S. suis-stimulated DCs also displayed sustained/upregulated levels of MARCH1/8, thus possibly leading to MHC-II lysosomal degradation. The bacterial capsular polysaccharide played a partial role in this modulation. Finally, interleukin (IL)-12p70 production was inhibited in splenic DCs from infected mice, a profile compatible with DC indirect activation by pro-inflammatory compounds. Consequently, these cells induced lower levels of IL-2 and TNF-α in an antigen-specific CD4+ T cell presentation assay and blunted T cell CD25 expression. It remains unclear at this stage whether these phenotypical and transcriptional modulations observed in response to S. suis in in vivo infections are part of a bacterial immune evasion strategy or rather a feature common to systemic inflammatory response-inducing agents. However, it appears that the MHC-II-restricted antigen presentation and Th1-polarizing cytokine production capacities of DCs are impaired during S. suis infection. This study highlights the potential consequences of inflammation on the type and magnitude of the immune response elicited by a pathogen. PMID:29899744

25 CFR 522.11 - Individually owned class II gaming operations operating on September 1, 1986.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Individually owned class II gaming operations operating on September 1, 1986. 522.11 Section 522.11 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR APPROVAL OF CLASS II AND CLASS III ORDINANCES AND RESOLUTIONS SUBMISSION OF GAMING...

Glass ionomer-silver cermet Class II tunnel-restorations for primary molars.

PubMed

Croll, T P

1988-01-01

Tunnel preparations preserve the anatomical marginal ridge and minimize the loss of healthy tooth structure adjacent to the carious lesion. When the practitioner has developed proficiency in restoring class II carious lesions with tunnel restorations, less treatment time is required than with traditional class II preparations. The technique for restoring a primary first molar with a class II carious lesion, using a tunnel preparation and Ketac-Silver restorative material is described.

Diversity and evolutionary patterns of immune genes in free-ranging Namibian leopards (Panthera pardus pardus).

PubMed

Castro-Prieto, Aines; Wachter, Bettina; Melzheimer, Joerg; Thalwitzer, Susanne; Sommer, Simone

2011-01-01

The genes of the major histocompatibility complex (MHC) are a key component of the mammalian immune system and have become important molecular markers for fitness-related genetic variation in wildlife populations. Currently, no information about the MHC sequence variation and constitution in African leopards exists. In this study, we isolated and characterized genetic variation at the adaptively most important region of MHC class I and MHC class II-DRB genes in 25 free-ranging African leopards from Namibia and investigated the mechanisms that generate and maintain MHC polymorphism in the species. Using single-stranded conformation polymorphism analysis and direct sequencing, we detected 6 MHC class I and 6 MHC class II-DRB sequences, which likely correspond to at least 3 MHC class I and 3 MHC class II-DRB loci. Amino acid sequence variation in both MHC classes was higher or similar in comparison to other reported felids. We found signatures of positive selection shaping the diversity of MHC class I and MHC class II-DRB loci during the evolutionary history of the species. A comparison of MHC class I and MHC class II-DRB sequences of the leopard to those of other felids revealed a trans-species mode of evolution. In addition, the evolutionary relationships of MHC class II-DRB sequences between African and Asian leopard subspecies are discussed.

77 FR 16123 - Draft Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

...; Class II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the... Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... II Special Controls Guidance Document: Nucleic Acid-Based In Vitro Diagnostic Devices for the...

Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation.

PubMed

Chaigne, Benjamin; Geneugelijk, Kirsten; Bédat, Benoît; Ahmed, Mohamed Alibashe; Hönger, Gideon; De Seigneux, Sophie; Demuylder-Mischler, Sandrine; Berney, Thierry; Spierings, Eric; Ferrari-Lacraz, Sylvie; Villard, Jean

2016-11-01

The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant. Eleven out of 18 patients (61.1%) in the islet group and 12 out of 26 patients (46.2%) in the pancreas group had anti-HLA antibodies. Six patients (33.3%) developed DSAs against HLA of the islets, and 10 patients (38.4%) developed DSAs against HLA of the pancreas. Most of the DSAs were at a low level. Several parameters such as gender, number of times cells were transplanted, HLA mismatch, eplet mismatch and PIRCHE-II numbers, rejection, and infection were analyzed. Only the number of PIRCHE-II was associated with the development of anti-HLA class II de novo DSAs. Overall, the development of de novo DSAs did not influence graft survival as estimated by insulin independence. Our results indicated that pretransplant DSAs at low levels do not restrict islet or pancreas transplantation [especially islet transplantation (27.8% vs. 15.4.%)]. De novo DSAs do occur at a similar rate in both pancreas and islet transplant recipients (mainly of class II), and the immunogenicity of donor HLA is a parameter that should be taken into consideration. When combined with an immunosuppressive regimen and close follow-up, development of low levels of DSAs was not found to result in reduced graft survival or graft function in the current study.

Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4+ T Cell Immunity

PubMed Central

Ascough, Stephanie; Ingram, Rebecca J.; Chu, Karen K.; Reynolds, Catherine J.; Musson, Julie A.; Doganay, Mehmet; Metan, Gökhan; Ozkul, Yusuf; Baillie, Les; Sriskandan, Shiranee; Moore, Stephen J.; Gallagher, Theresa B.; Dyson, Hugh; Williamson, E. Diane; Robinson, John H.; Maillere, Bernard; Boyton, Rosemary J.; Altmann, Daniel M.

2014-01-01

Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified. PMID:24788397

Comparison of temporomandibular joint and ramus morphology between class II and class III cases before and after bi-maxillary osteotomy.

PubMed

Iguchi, Ran; Yoshizawa, Kunio; Moroi, Akinori; Tsutsui, Takamitsu; Hotta, Asami; Hiraide, Ryota; Takayama, Akihiro; Tsunoda, Tatsuya; Saito, Yuki; Sato, Momoko; Baba, Nana; Ueki, Koichiro

2017-12-01

The purpose of this study was to compare changes in temporomandibular joint (TMJ) and ramus morphology between class II and III cases before and after sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. The subjects were 39 patients (78 sides) who underwent bi-maxillary surgery. They consisted of 2 groups (18 class II cases and 21 class III cases), and were selected randomly from among patients who underwent surgery between 2012 and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus inclination and condylar square were assessed by computed tomography (CT), pre- and post-operatively. The number of joints with anterior disc displacement in class II was significantly higher than that in class III (p < 0.0001). However, there were no significant differences between the two classes regarding ratio of joint symptoms and ratio of joint effusion pre- and post-operatively. Class II was significantly better than class III regarding reduction ratio of condylar height (p < 0.0001) and square (p = 0.0005). The study findings suggest that condylar morphology could change in both class II and III after bi-maxillary surgery. The findings of the numerical analysis also demonstrated that reduction of condylar volume occurred frequently in class II, although TMJ disc position classification did not change significantly, as previously reported. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Resonance Properties of Class I and Class II Neurons Differentially Modulated by Channel Noise

NASA Astrophysics Data System (ADS)

Wang, Lei

2018-01-01

Resonance properties of two different neuron types (Class I and Class II) induced by channel noise are investigated in this study. It is found that for Class I neuron, spiking activity is enhanced when certain noise intensity is presented, especially under weak current stimuli -- a typical phenomenon of stochastic resonance (SR); while for Class II neuron, in addition to perform the SR, certain noise intensity would inhibit neuronal activity under some current stimuli -- a typical phenomenon of inverse stochastic resonance (ISR). Moreover, we show that only sodium channel noise or potassium channel noise variation can achieve the similar phenomena. Consequently, the model results suggest that channel noise may exert differential roles in modulating the resonance properties of Class I and Class II neurons.

11 CFR 114.3 - Disbursements for communications to the restricted class in connection with a Federal election.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 11 Federal Elections 1 2010-01-01 2010-01-01 false Disbursements for communications to the... communications to the restricted class in connection with a Federal election. (a) General. (1) Corporations and labor organizations may make communications on any subject, including communications containing express...

Multiple factors govern the association between pharmacology and toxicity in a class of drugs: toward a unification of class effect terminology.

PubMed

Smith, Dennis A; Harrison, Anthony; Morgan, Paul

2011-04-18

The term class effect has gained in use to describe a side effect including toxicity common to a series of drugs. There is no definition of what constitutes a class effect, and it is not applied against a rigid set of criteria.Thus, the finding of toxicity in one of a series of drugs can raise the concern of a class effect, especially if one or more of the others shows findings even slightly related or at very much lower incidence. This is particularly problematic when the term is used loosely or speculatively on initial events that are themselves of low incidence and serious. This speculation exaggerates and distorts the scientific process in establishing the true benefit risk of the individual drugs and can lead to lengthy development times, or highly restrictive labeling, to the detriment of patient welfare. To provide better definition and application of the term, we suggest that the term class effect toxicity is only used when a clear mechanistic link has been established between a safety concern and drug class based on (I) where the primary pharmacology delivers a clear rationale for the observed findings and toxicities; and (II) where the secondary pharmacology is obligate to the class of the molecule and not subject to variation of structure, and the selectivity cannot be impacted significantly by variations in potency introduced by structural manipulation. With these categorizations, we believe class effect toxicity will be mainly confined to I with examples such as the tetracycline class of antibacterials which inhibit protein synthesis both as a mechanism of antibacterial activity and to produce hepatic injury by mitochondrial injury in the liver.

Thin-plate spline analysis of craniofacial growth in Class I and Class II subjects.

PubMed

Franchi, Lorenzo; Baccetti, Tiziano; Stahl, Franka; McNamara, James A

2007-07-01

To compare the craniofacial growth characteristics of untreated subjects with Class II division 1 malocclusion with those of subjects with normal (Class I) occlusion from the prepubertal through the postpubertal stages of development. The Class II division 1 sample consisted of 17 subjects (11 boys and six girls). The Class I sample also consisted of 17 subjects (13 boys and four girls). Three craniofacial regions (cranial base, maxilla, and mandible) were analyzed on the lateral cephalograms of the subjects in both groups by means of thin-plate spline analysis at T1 (prepubertal) and T2 (postpubertal). Both cross-sectional and longitudinal comparisons were performed on both size and shape differences between the two groups. The results showed an increased cranial base angulation as a morphological feature of Class II malocclusion at the prepubertal developmental phase. Maxillary changes in either shape or size were not significant. Subjects with Class II malocclusion exhibited a significant deficiency in the size of the mandible at the completion of active craniofacial growth as compared with Class I subjects. A significant deficiency in the size of the mandible became apparent in Class II subjects during the circumpubertal period and it was still present at the completion of active craniofacial growth.

Influence of pharyngeal airway respiration pressure on Class II mandibular retrusion in children: A computational fluid dynamics study of inspiration and expiration.

PubMed

Iwasaki, T; Sato, H; Suga, H; Takemoto, Y; Inada, E; Saitoh, I; Kakuno, K; Kanomi, R; Yamasaki, Y

2017-05-01

To examine the influence of negative pressure of the pharyngeal airway on mandibular retraction during inspiration in children with nasal obstruction using the computational fluid dynamics (CFD) method. Sixty-two children were divided into Classes I, II (mandibular retrusion) and III (mandibular protrusion) malocclusion groups. Cone-beam computed tomography data were used to reconstruct three-dimensional shapes of the nasal and pharyngeal airways. Airflow pressure was simulated using CFD to calculate nasal resistance and pharyngeal airway pressure during inspiration and expiration. Nasal resistance of the Class II group was significantly higher than that of the other two groups, and oropharyngeal airway inspiration pressure in the Class II (-247.64 Pa) group was larger than that in the Class I (-43.51 Pa) and Class III (-31.81 Pa) groups (P<.001). The oropharyngeal airway inspiration-expiration pressure difference in the Class II (-27.38 Pa) group was larger than that in the Class I (-5.17 Pa) and Class III (0.68 Pa) groups (P=.006). Large negative inspiratory pharyngeal airway pressure due to nasal obstruction in children with Class II malocclusion may be related to their retrognathia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Disruption of HLA class II antigen presentation in Burkitt lymphoma: implication of a 47 000 MW acid labile protein in CD4+ T-cell recognition

PubMed Central

God, Jason M; Zhao, Dan; Cameron, Christine A; Amria, Shereen; Bethard, Jennifer R; Haque, Azizul

2014-01-01

While Burkitt lymphoma (BL) has a well-known defect in HLA class I-mediated antigen presentation, the exact role of BL-associated HLA class II in generating a poor CD4+ T-cell response remains unresolved. Here, we found that BL cells are deficient in their ability to optimally stimulate CD4+ T cells via the HLA class II pathway. This defect in CD4+ T-cell recognition was not associated with low levels of co-stimulatory molecules on BL cells, as addition of external co-stimulation failed to elicit CD4+ T-cell activation by BL. Further, the defect was not caused by faulty antigen/class II interaction, because antigenic peptides bound with measurable affinity to BL-associated class II molecules. Interestingly, functional class II–peptide complexes were formed at acidic pH 5·5, which restored immune recognition. Acidic buffer (pH 5·5) eluate from BL cells contained molecules that impaired class II-mediated antigen presentation and CD4+ T-cell recognition. Biochemical analysis showed that these molecules were greater than 30 000 molecular weight in size, and proteinaceous in nature. In addition, BL was found to have decreased expression of a 47 000 molecular weight enolase-like molecule that enhances class II-mediated antigen presentation in B cells, macrophages and dendritic cells, but not in BL cells. These findings demonstrate that BL likely has multiple defects in HLA class II-mediated antigen presentation and immune recognition, which may be exploited for future immunotherapies. PMID:24628049

Re-evaluating the generation of a "proteasome-independent" MHC class I-restricted CD8 T cell epitope.

PubMed

Wherry, E John; Golovina, Tatiana N; Morrison, Susan E; Sinnathamby, Gomathinayagam; McElhaugh, Michael J; Shockey, David C; Eisenlohr, Laurence C

2006-02-15

The proteasome is primarily responsible for the generation of MHC class I-restricted CTL epitopes. However, some epitopes, such as NP(147-155) of the influenza nucleoprotein (NP), are presented efficiently in the presence of proteasome inhibitors. The pathways used to generate such apparently "proteasome-independent" epitopes remain poorly defined. We have examined the generation of NP(147-155) and a second proteasome-dependent NP epitope, NP(50-57), using cells adapted to growth in the presence of proteasome inhibitors and also through protease overexpression. We observed that: 1) Ag processing and presentation proceeds in proteasome-inhibitor adapted cells but may become more dependent, at least in part, on nonproteasomal protease(s), 2) tripeptidyl peptidase II does not substitute for the proteasome in the generation of NP(147-155), 3) overexpression of leucine aminopeptidase, thymet oligopeptidase, puromycin-sensitive aminopeptidase, and bleomycin hydrolase, has little impact on the processing and presentation of NP(50-57) or NP(147-155), and 4) proteasome-inhibitor treatment altered the specificity of substrate cleavage by the proteasome using cell-free digests favoring NP(147-155) epitope preservation. Based on these results, we propose a central role for the proteasome in epitope generation even in the presence of proteasome inhibitors, although such inhibitors will likely alter cleavage patterns and may increase the dependence of the processing pathway on postproteasomal enzymes.

Sibling rivalry: competition between MHC class II family members inhibits immunity.

PubMed

Denzin, Lisa K; Cresswell, Peter

2013-01-01

Peptide loading of major histocompatibility complex (MHC) class II molecules in the endosomes and lysosomes of antigen-presenting cells is catalyzed by human leukocyte antigen-DM (HLA-DM) and modulated by HLA-DO. In a structural study in this issue, Guce et al. show that HLA-DO is an MHC class II mimic and functions as a competitive and essentially irreversible inhibitor of HLA-DM activity, thereby inhibiting MHC class II antigen presentation.

Factors associated with prescribing restriction on oncology formulary drugs in Malaysia.

PubMed

Fatokun, Omotayo; Olawepo, Michael N

2016-10-01

Background Drugs listed on formularies are often subjected to a variety of utilization restriction measures. However, the degree of restriction is influenced by multiple factors, including the characteristics and attributes of the listed drugs. Objective To identify the factors that are associated with the levels of prescribing restriction on oncology formulary drugs in Malaysia. Setting Oncology formulary in Malaysia. Method The Malaysia Drug Code assigned to each of the drug products on the Malaysia Ministry of Health (MOH) drug formulary was used to identify oncology drugs belonging to WHO ATC class L (antineoplastic and immunomodulating agents). Main outcome measures Categories of prescribing restrictions, therapeutic class, drug type, administration mode, number of sources and the post-approval use period. Results Oncology drugs having a shorter post-approval use period (p < 0.001), biologic oncology drugs (p = 0.01) and oncology drugs belonging to immunosuppressant therapeutic class (p = 0.03) were all significantly associated with a greater likelihood of being subjected to a higher level of prescribing restriction. Conclusion This study suggests that safety concerns, costs and potentials for inappropriate use were the important considerations influencing a higher level of prescribing restriction placement on oncology drugs in the Malaysia MOH drug formulary.

Restrictive transfusion threshold is safe in high-risk patients undergoing brain tumor surgery.

PubMed

Alkhalid, Yasmine; Lagman, Carlito; Sheppard, John P; Nguyen, Thien; Prashant, Giyarpuram N; Ziman, Alyssa F; Yang, Isaac

2017-12-01

To assess the safety of a restrictive threshold for the transfusion of red blood cells (RBCs) compared to a liberal threshold in high-risk patients undergoing brain tumor surgery. We reviewed patients who were 50 years of age or older with a preoperative American Society of Anesthesiologists physical status class II to V who underwent open craniotomy for tumor resection and were transfused packed RBCs during or after surgery. We retrospectively assigned patients to a restrictive-threshold (a pretransfusion hemoglobin level <8g/dL) or a liberal-threshold group (a pretransfusion hemoglobin level of 8-10/dL). The primary outcome was in-hospital mortality rate. Secondary outcomes were in-hospital complication rates, length of stay, and discharge disposition. Twenty-five patients were included in the study, of which 17 were assigned to a restrictive-threshold group and 8 patients to a liberal-threshold group. The in-hospital mortality rates were 12% for the restrictive-threshold group (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.07-12.11) and 13% for the liberal-threshold group. The in-hospital complication rates were 52.9% for the restrictive-threshold group (OR 1.13, 95% CI 0.21-6.05) and 50% for the liberal-threshold group. The average number of days in the intensive care unit and hospital were 8.6 and 22.4 days in the restrictive-threshold group and 6 and 15 days in the liberal-threshold group, respectively (P=0.69 and P=0.20). The rates of non-routine discharge were 71% in the restrictive-threshold group (OR 2.40, 95% CI 0.42-13.60) and 50% in the liberal-threshold group. A restrictive transfusion threshold did not significantly influence in-hospital mortality or complication rates, length of stay, or discharge disposition in patients at high operative risk. Copyright © 2017. Published by Elsevier B.V.

Restriction enzyme body doubles and PCR cloning: on the general use of type IIs restriction enzymes for cloning.

PubMed

Tóth, Eszter; Huszár, Krisztina; Bencsura, Petra; Kulcsár, Péter István; Vodicska, Barbara; Nyeste, Antal; Welker, Zsombor; Tóth, Szilvia; Welker, Ervin

2014-01-01

The procedure described here allows the cloning of PCR fragments containing a recognition site of the restriction endonuclease (Type IIP) used for cloning in the sequence of the insert. A Type IIS endonuclease--a Body Double of the Type IIP enzyme--is used to generate the same protruding palindrome. Thus, the insert can be cloned to the Type IIP site of the vector without digesting the PCR product with the same Type IIP enzyme. We achieve this by incorporating the recognition site of a Type IIS restriction enzyme that cleaves the DNA outside of its recognition site in the PCR primer in such a way that the cutting positions straddle the desired overhang sequence. Digestion of the PCR product by the Body Double generates the required overhang. Hitherto the use of Type IIS restriction enzymes in cloning reactions has only been used for special applications, the approach presented here makes Type IIS enzymes as useful as Type IIP enzymes for general cloning purposes. To assist in finding Body Double enzymes, we summarised the available Type IIS enzymes which are potentially useful for Body Double cloning and created an online program (http://group.szbk.u-szeged.hu/welkergr/body_double/index.html) for the selection of suitable Body Double enzymes and the design of the appropriate primers.

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

25 CFR 547.9 - What are the minimum technical standards for Class II gaming system accounting functions?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.9 What are the minimum technical standards for Class II gaming system... digits to accommodate the design of the game. (3) Accounting data displayed to the player may be... audit, configuration, recall and test modes; or (ii) Temporarily, during entertaining displays of game...

Finishing occlusion in Class II or Class III molar relation: therapeutic Class II and III.

PubMed

Nangia, A; Darendeliler, M A

2001-11-01

The most frequent extraction regime consists of the removal of upper and lower premolars. Depending on anchorage requirements, camouflage treatment options, surgical intervention, or the absence of teeth in only one arch, it may become necessary to finalize the occlusion with a one-dental-unit discrepancy between the upper and lower dental arches. Guidelines are presented for finishing occlusions in Class II or Class III molar relation.

Evolution and Distribution of Class II-Related Endogenous Retroviruses†

PubMed Central

Gifford, Robert; Kabat, Peter; Martin, Joanne; Lynch, Clare; Tristem, Michael

2005-01-01

Endogenous retroviruses (ERVs) are widespread in vertebrate genomes and have been loosely grouped into “classes” on the basis of their phylogenetic relatedness to the established genera of exogenous retroviruses. Four of these genera—the lentiviruses, alpharetroviruses, betaretroviruses, and deltaretroviruses—form a well-supported clade in retroviral phylogenies, and ERVs that group with these genera have been termed class II ERVs. We used PCR amplification and sequencing of retroviral fragments from more than 130 vertebrate taxa to investigate the evolution of the class II retroviruses in detail. We confirm that class II retroviruses are largely confined to mammalian and avian hosts and provide evidence for a major novel group of avian retroviruses, and we identify additional members of both the alpha- and the betaretrovirus genera. Phylogenetic analyses demonstrated that the avian and mammalian viruses form distinct monophyletic groups, implying that interclass transmission has occurred only rarely during the evolution of the class II retroviruses. In contrast to previous reports, the lentiviruses clustered as sister taxa to several endogenous retroviruses derived from rodents and insectivores. This topology was further supported by the shared loss of both the class II PR-Pol frameshift site and the class II retrovirus G-patch domain. PMID:15858031

Variations in tooth size and arch dimensions in Malay schoolchildren.

PubMed

Hussein, Khalid W; Rajion, Zainul A; Hassan, Rozita; Noor, Siti Noor Fazliah Mohd

2009-11-01

To compare the mesio-distal tooth sizes and dental arch dimensions in Malay boys and girls with Class I, Class II and Class III malocclusions. The dental casts of 150 subjects (78 boys, 72 girls), between 12 and 16 years of age, with Class I, Class II and Class III malocclusions were used. Each group consisted of 50 subjects. An electronic digital caliper was used to measure the mesio-distal tooth sizes of the upper and lower permanent teeth (first molar to first molar), the intercanine and intermolar widths. The arch lengths and arch perimeters were measured with AutoCAD software (Autodesk Inc., San Rafael, CA, U.S.A.). The mesio-distal dimensions of the upper lateral incisors and canines in the Class I malocclusion group were significantly smaller than the corresponding teeth in the Class III and Class II groups, respectively. The lower canines and first molars were significantly smaller in the Class I group than the corresponding teeth in the Class II group. The lower intercanine width was significantly smaller in the Class II group as compared with the Class I group, and the upper intermolar width was significantly larger in Class III group as compared with the Class II group. There were no significant differences in the arch perimeters or arch lengths. The boys had significantly wider teeth than the girls, except for the left lower second premolar. The boys also had larger upper and lower intermolar widths and lower intercanine width than the girls. Small, but statistically significant, differences in tooth sizes are not necessarily accompanied by significant arch width, arch length or arch perimeter differences. Generally, boys have wider teeth, larger lower intercanine width and upper and lower intermolar widths than girls.

A method to discriminate between closely related bovine major histocompatibility complex class I alleles by combining established PCR-SSP assays with RFLPs.

PubMed

Svitek, N; Nzau, B; Steinaa, L; Nene, V

2015-04-01

We have developed a polymerase chain reaction-sequence-specific primers-restriction fragment length polymorphism (PCR-SSP-RFLP) method to rapidly differentiate between the A18 and A18 variant (v) BoLA haplotypes and between A14 and A15/A15v BoLA haplotypes in Holstein/Friesian cattle. We used published SSP to PCR amplify BoLA alleles expressed in animals of known haplotype and exposed the amplicons to the restriction enzyme PvuII that was predicted to cut at a unique site in the middle of BoLA-6*01302 (A18v) and BoLA-1*00901 (A15) but not in BoLA-6*01301 (A18) or BoLA-1*02301 (A14) alleles. Whereas the method does not discriminate between the A15 and A15v haplotypes, as the BoLA-1*00902 allele associated with A15v also contains a PvuII site, we are interested in cattle of A18 and A14 haplotype for vaccine related studies. Our results also indicated that the BoLA-6*01302 (A18v) allele is much more abundant than BoLA-6*01301 (A18) in the cattle that we sampled. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

MYCIN II: design and implementation of a therapy reference with complex content-based indexing.

PubMed Central

Kim, D. K.; Fagan, L. M.; Jones, K. T.; Berrios, D. C.; Yu, V. L.

1998-01-01

We describe the construction of MYCIN II, a prototype system that provides for content-based markup and search of a forthcoming clinical therapeutics textbook, Antimicrobial Therapy and Vaccines. Existing commercial search technology for digital references utilizes generic tools such as textword-based searches with geographical or statistical refinements. We suggest that the drawbacks of such systems significantly restrict their use in everyday clinical practice. This is in spite of the fact that there is a great need for the information contained within these same references. The system we describe is intended to supplement keyword searching so that certain important questions can be asked easily and can be answered reliably (in terms of precision and recall). Our method attacks this problem in a restricted domain of knowledge-clinical infectious disease. For example, we would like to be able to answer the class of questions exemplified by the following query: "What antimicrobial agents can be used to treat endocarditis caused by Eikenella corrodens?" We have compiled and analyzed a list of such questions to develop a concept-based markup scheme. This scheme was then applied within an HTML markup to electronically "highlight" passages from three textbook chapters. We constructed a functioning web-based search interface. Our system also provides semi-automated querying of PubMed using our concept markup and the user's actions as a guide. PMID:9929205

MYCIN II: design and implementation of a therapy reference with complex content-based indexing.

PubMed

Kim, D K; Fagan, L M; Jones, K T; Berrios, D C; Yu, V L

1998-01-01

We describe the construction of MYCIN II, a prototype system that provides for content-based markup and search of a forthcoming clinical therapeutics textbook, Antimicrobial Therapy and Vaccines. Existing commercial search technology for digital references utilizes generic tools such as textword-based searches with geographical or statistical refinements. We suggest that the drawbacks of such systems significantly restrict their use in everyday clinical practice. This is in spite of the fact that there is a great need for the information contained within these same references. The system we describe is intended to supplement keyword searching so that certain important questions can be asked easily and can be answered reliably (in terms of precision and recall). Our method attacks this problem in a restricted domain of knowledge-clinical infectious disease. For example, we would like to be able to answer the class of questions exemplified by the following query: "What antimicrobial agents can be used to treat endocarditis caused by Eikenella corrodens?" We have compiled and analyzed a list of such questions to develop a concept-based markup scheme. This scheme was then applied within an HTML markup to electronically "highlight" passages from three textbook chapters. We constructed a functioning web-based search interface. Our system also provides semi-automated querying of PubMed using our concept markup and the user's actions as a guide.

77 FR 50760 - Notice and request for comments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

... rehabilitation to Class II and Class III railroad infrastructure damaged by hurricanes, floods, and natural... issued by the President ( http://www.fema.gov/news/disasters.fema#sev1 ). Class II and Class III railroad...

Polymorphism at Expressed DQ and DR Loci in Five Common Equine MHC Haplotypes

PubMed Central

Miller, Donald; Tallmadge, Rebecca L.; Binns, Matthew; Zhu, Baoli; Mohamoud, Yasmin Ali; Ahmed, Ayeda; Brooks, Samantha A.; Antczak, Douglas F.

2016-01-01

The polymorphism of Major Histocompatibility Complex (MHC) class II DQ and DR genes in five common Equine Leukocyte Antigen (ELA) haplotypes was determined through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA homozygous horses. Ten expressed MHC class II genes were detected in horses of the ELA-A3 haplotype carried by the donor horses of the equine Bacterial Artificial Chromosome (BAC) library and the reference genome sequence: four DR genes and six DQ genes. The other four ELA haplotypes contained at least eight expressed polymorphic MHC class II loci. Next Generation Sequencing (NGS) of genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the other MHC class II genes that were not amplified in these horses. The amino acid sequences across haplotypes contained locus-specific residues, and the locus clusters produced by phylogenetic analysis were well supported. The MHC class II alleles within the five tested haplotypes were largely non-overlapping between haplotypes. The complement of equine MHC class II DQ and DR genes appears to be well conserved between haplotypes, in contrast to the recently described variation in class I gene loci between equine MHC haplotypes. The identification of allelic series of equine MHC class II loci will aid comparative studies of mammalian MHC conservation and evolution and may also help to interpret associations between the equine MHC class II region and diseases of the horse. PMID:27889800

40 CFR 82.23 - Transfers of allowances of class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., any production, and allowable imports and exports of class II controlled substances reported by the... quantity of the transferor's class II consumption allowances, production allowances, export production... EPA; and (G) For trades of consumption allowances, production allowances, export production allowances...

Interaction of Mycobacterium avium-containing phagosomes with the antigen presentation pathway.

PubMed

Ullrich, H J; Beatty, W L; Russell, D G

2000-12-01

Pathogenic mycobacteria infect macrophages where they replicate in phagosomes that minimize contact with late endosomal/lysosomal compartments. Loading of Ags to MHC class II molecules occurs in specialized compartments with late endosomal characteristics. This points to a sequestration of mycobacteria-containing phagosomes from the sites where Ags meet MHC class II molecules. Indeed, in resting macrophages MHC class II levels decreased strongly in phagosomes containing M. avium during a 4-day infection. Phagosomal MHC class II of early (4 h) infections was partly surface-derived and associated with peptide. Activation of host macrophages led to the appearance of H2-M, a chaperon of Ag loading, and to a strong increase in MHC class II molecules in phagosomes of acute (1 day) infections. Comparison with the kinetics of MHC class II acquisition by IgG-coated bead-containing phagosomes suggests that the arrest in phagosome maturation by mycobacteria limits the intersection of mycobacteria-containing phagosomes with the intracellular trafficking pathways of Ag-presenting molecules.

Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow fever virus structural proteins and BALB/c (H2d) mice model.

PubMed

Maciel, Milton; Kellathur, Srinivasan N; Chikhlikar, Pryia; Dhalia, Rafael; Sidney, John; Sette, Alessandro; August, Thomas J; Marques, Ernesto T A

2008-08-15

Immunomics research uses in silico epitope prediction, as well as in vivo and in vitro approaches. We inoculated BALB/c (H2d) mice with 17DD yellow fever vaccine to investigate the correlations between approaches used for epitope discovery: ELISPOT assays, binding assays, and prediction software. Our results showed a good agreement between ELISPOT and binding assays, which seemed to correlate with the protein immunogenicity. PREDBALB/c prediction software partially agreed with the ELISPOT and binding assay results, but presented low specificity. The use of prediction software to exclude peptides containing no epitopes, followed by high throughput screening of the remaining peptides by ELISPOT, and the use of MHC-biding assays to characterize the MHC restrictions demonstrated to be an efficient strategy. The results allowed the characterization of 2 MHC class I and 17 class II epitopes in the envelope protein of the YF virus in BALB/c (H2d) mice.

Bone-anchored intermaxillary elastics in an asymmetric Class II malocclusion: A case report.

PubMed

Manni, Antonio; Lupini, Daniela; Cozzani, Mauro

2017-06-01

A 13-year-old male patient, presenting a Class II, division 1 malocclusion and crowding was treated by an innovative technique. After rapid palatal expansion by a Hyrax appliance, the teeth were bonded with straightwire brackets. Two miniscrews were inserted, one per side, in the mandibular buccal bone between the roots of the mandibular first molar and the second premolar. On the right side, the miniscrew implant was connected to the hook clamped on a 0.021×0.028″ SS wire with a twisted SS ligature in order to maintain the inclination of the frontal incisors during the Class II mechanics. On the left side, where the Class II relationship was more marked, intermaxillary elastics were applied from the upper left hook clamped on the archwire to the lower first molar and a power chain (100g) was stretched from the lower left hook to the miniscrew implant. Class II correction was accomplished using sequential Class II elastics of progressive strength coupled with rectangular stainless steel wires. After 22 months of active treatment, the results were balanced facial esthetics and a good occlusion. This dual anchorage set-up of Class II elastics reinforced with TADs produced protrusive action on the mandible with minimal side effects and with no significant change in the vertical dimension during the sagittal correction of the Class II malocclusion. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

Detection of novel cancer-testis antigen-specific T-cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma.

PubMed

Mizukami, Yoshiki; Kono, Koji; Daigo, Yataro; Takano, Atsushi; Tsunoda, Takuya; Kawaguchi, Yoshihiko; Nakamura, Yusuke; Fujii, Hideki

2008-07-01

We recently identified three HLA-A2402-restricted epitope peptides derived from cancer-testis antigens (CTA), TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3) for the development of immunotherapies against esophageal squamous cell carcinoma (ESCC). In order to evaluate their immunotherapeutic potential in ESCC patients, we estimated by ELISPOT assay the TTK-, LY6K-, or IMP-3-specific T-cell immune responses in tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) expanded from 20HLA-A2402 (+) ESCC patients, and correlated their immune activity with the expression levels of TTK, LY6K, and IMP-3, and MHC class I in the tumors. Induction of TTK-antigen specific T-cell response in TIL to the peptide-pulsed target cells was detected in 14 out of 20 (70%) cases, while LY6K or IMP-3 specific T-cell activity was observed in 11 of 20 (55%) or in eight of 20 (40%) cases, respectively. Furthermore, T-cell activity in RLNL and PBL was detectable in the similar proportion of the 20 ESCC patients. Interestingly, CTA-specific T-cell immune response was found in 13 of 14 (93%) TIL obtained from ESCC tumors with strong MHC class I expression, while it could be observed only in two of six (33%) TIL from ESCC tumors with weak MHC class I expression. These results strongly suggest the pre-existence of specific T-cell responses to HLA-A24-restricted epitope peptides from TTK, LY6K, and IMP-3 in ESCC patients. Monitoring antigen-specific T-cell responses, as well as the expression levels of MHC class I and epitope CTA in tumors, should be a selection index for application of cancer vaccine therapies to the patients who are likely to show good immune response.

Anteroposterior condylar position: a comparative study between subjects with normal occlusion and patients with Class I, Class II Division 1, and Class III malocclusions.

PubMed

Fraga, Marcelo Reis; Rodrigues, Andréia Fialho; Ribeiro, Luiz Claudio; Campos, Marcio José da Silva; Vitral, Robert Willer Farinazzo

2013-10-29

The present study aimed to determine and compare the anteroposterior position of the condyle in the mandibular fossa between groups of asymptomatic subjects with normal occlusion and asymptomatic subjects with Class I, Class II Division 1, and Class III malocclusions. Thirty persons with normal occlusion, 30 with Class I malocclusion, 30 with Class II Division 1, and 30 with Class III had computed tomography scans of their temporomandibular joints. The anterior joint space/posterior joint space (AJS/PJS) ratio was determined for the right and left joints. The paired t test was used to analyze the AJS/PJS ratio between both sides for each group. The ANOVA test was applied to verify the differences between the groups for the measurements of the right and left sides. In case the ANOVA test confirmed significance, the Dunnett's t test was performed to compare the groups of malocclusion with that of normal occlusion. The paired t test between the AJS/PJS relationships in the right and left sides showed the following p values: Class I (0.168), Class II Division 1 (0.662), Class III (0.991), and normal occlusion (0.390). The ANOVA test showed a p value of 0.445 for the comparisons of the right side and 0.040 for the left side. The Dunnett's t test demonstrated a statistically significant difference between the Class II group and the normal occlusion group (p value of 0.026) in the joints of the left side. Bilateral symmetry and lack of condyle centralization were common characteristics among all groups. The greatest condylar decentralization was observed in the Class II group, whereas the least condylar decentralization was found in the normal occlusion group.

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant.

PubMed

Kamburova, E G; Wisse, B W; Joosten, I; Allebes, W A; van der Meer, A; Hilbrands, L B; Baas, M C; Spierings, E; Hack, C E; van Reekum, F E; van Zuilen, A D; Verhaar, M C; Bots, M L; Drop, A C A D; Plaisier, L; Seelen, M A J; Sanders, J S F; Hepkema, B G; Lambeck, A J A; Bungener, L B; Roozendaal, C; Tilanus, M G J; Voorter, C E; Wieten, L; van Duijnhoven, E M; Gelens, M; Christiaans, M H L; van Ittersum, F J; Nurmohamed, S A; Lardy, N M; Swelsen, W; van der Pant, K A; van der Weerd, N C; Ten Berge, I J M; Bemelman, F J; Hoitsma, A; van der Boog, P J M; de Fijter, J W; Betjes, M G H; Heidt, S; Roelen, D L; Claas, F H; Otten, H G

2018-02-21

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10-year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10-year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10-year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence. © 2018 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

7 CFR 1000.53 - Announcement of class prices, component prices, and advanced pricing factors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... order) for the preceding month: (1) The Class II price; (2) The Class II butterfat price; (3) The Class... the following month: (1) The Class I price; (2) The Class I skim milk price; (3) The Class I butterfat...; (7) The butterfat price; (8) The nonfat solids price; (9) The protein price; (10) The other solids...

Comparison of BMI, AHI, and apolipoprotein E ε4 (APOE-ε4) alleles among sleep apnea patients with different skeletal classifications.

PubMed

Roedig, Jason J; Phillips, Barbara A; Morford, Lorri A; Van Sickels, Joseph E; Falcao-Alencar, Gabriel; Fardo, David W; Hartsfield, James K; Ding, Xiuhua; Kluemper, G Thomas

2014-04-15

This case-control study investigated whether variations within the APOE-ε gene were associated with having a convex facial profile (skeletal Class II) compared to exhibiting a straight or concave facial profile (Class I or Class III) among patients with obstructive sleep apnea (OSA). Associations between the apnea-hypopnea index (AHI) and body mass index (BMI) scores for these OSA patients were also examined in the context of facial profile. OSA patients with an AHI ≥ 15 were recruited from a sleep clinic and classified by facial and dental occlusal relationships based on a profile facial analysis, lateral photographs, and dental examination. Saliva was collected as a source of DNA. The APOE-ε1-4 allele-defining single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped. A χ(2) analysis was used to assess Hardy-Weinberg equilibrium and for association analysis (significance at p < 0.05). ANOVA and Fisher exact test were also used. Seventy-six Caucasian OSA patients participated in the study-25 Class II cases and 51 non-Class II cases. There was no association of the APOE-ε4 allele with facial profile among these OSA patients. Class II OSA patients had significantly lower BMIs (30.7 ± 5.78) than Class I (37.3 ± 6.14) or Class III (37.8 ± 6.17) patients (p < 0.001), although there was no statistical difference in AHI for Class II patients compared with other groups. OSA patients with Class II convex profile were more likely to have a lower BMI than those in other skeletal groups. In fact 20% of them were not obese, suggesting that a Class II convex profile may influence or be associated with OSA development independent of BMI.

A cephalometric analysis of Class II dentate subjects to establish a formula to determine the occlusal plane in Class II edentate subjects: A neo adjunct.

PubMed

Sinha, Nikita; Reddy, K Mahendranadh; Gupta, Nidhi; Shastry, Y M

2017-01-01

Occlusal plane (OP) differs considerably in participants with skeletal Class I and Class II participants. In this study, cephalometrics has been used to help in the determination of orientation of the OP utilizing the nonresorbable bony anatomic landmarks in skeletal Class II participants and an attempt has been made to predict and examine the OP in individuals with skeletal class II jaw relationship. One hundred dentulous participants with skeletal Class II malocclusion who came to the hospital for correcting their jaw relationship participated in the study. Their right lateral cephalogram was taken using standardized procedures, and all the tracings were manually done by a single trained examiner. The cephalograms which were taken for the diagnostic purpose were utilized for the study, and the patient was not exposed to any unnecessary radiation. The numerical values obtained from the cephalograms were subjected to statistical analysis. Pearson's correlation of <0.001 was considered significant, and a linear regression analysis was performed to determine a formula which would help in the determination of orientation of the OP in Class II edentulous participants. Pearson's correlation coefficient and linear regression analysis were performed, and a high correlation was found between A2 and (A2 + B2)/(B2 + C2) with " r " value of 0.5. A medium correlation was found between D2 and (D2 + E2)/(E2 + F2) with " r " value of 0.42. The formula obtained for posterior reference frame through linear regression equation was y = 0.018* × +0.459 and the formula obtained for anterior reference frame was y1 = 0.011* × 1 + 0.497. It was hypothesized that by substituting these formulae in the cephalogram obtained from the Class II edentate individual, the OP can be obtained and verified. It was concluded that cephalometrics can be useful in examining the orientation of OP in skeletal Class II participants.

Restriction fragment length polymorphism within the class I gene loci of the equine major histocompatibility complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, A.J.; Bailey, E.; Woodward, J.G.

1986-03-05

Fourteen standard bred horses were serotyped as homozygous for 1 of 6 Equine Leukocyte Antigen (ELA) specificities. DNA was purified from peripheral leukocytes and digested with Hind III or Pvu II. Southern blot hybridization analysis was carried out using a /sup 32/P-labeled mouse cDNA probe (PH2IIa) specific for class I MHC genes. Both enzymes generated blots that contained a large number of bands (23 to 30) per horse. Significant polymorphism existed among most fragment sizes, while a dozen highly conserved band sizes suggested the presence of Qa/tla - like genes. Only 2 animals (both W6's) showed identical band patterns. Polymorphismmore » was greatest between horses of different serotypes and was significantly decreased within serotypes. Unique bands were present on both blots for both W1's and W6's and may account for the serologic specificity seen in ELA W1 and W6 horses. This study is consistent with the findings in other higher vertebrates and implies that the MHC of the horse includes a highly polymorphic class I multigene family.« less

Latent Class Analysis of Incomplete Data via an Entropy-Based Criterion

PubMed Central

Larose, Chantal; Harel, Ofer; Kordas, Katarzyna; Dey, Dipak K.

2016-01-01

Latent class analysis is used to group categorical data into classes via a probability model. Model selection criteria then judge how well the model fits the data. When addressing incomplete data, the current methodology restricts the imputation to a single, pre-specified number of classes. We seek to develop an entropy-based model selection criterion that does not restrict the imputation to one number of clusters. Simulations show the new criterion performing well against the current standards of AIC and BIC, while a family studies application demonstrates how the criterion provides more detailed and useful results than AIC and BIC. PMID:27695391

77 FR 32465 - Technical Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-01

... minimum odds for Class II games; amend standards for test labs; remove references to the Federal... the Play of Class II Games. 73 FR 60508. The rule added a new part to the Commission's regulations establishing a process for ensuring the integrity of electronic Class II games and aids. The standards were...

40 CFR 147.1600 - State-administered program-Class II wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS New Mexico § 147.1600 State-administered program—Class II wells. The UIC program for Class II wells in the State of New Mexico, except for those on Indian lands, is the program administered by the New...

40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized by...

40 CFR 144.22 - Existing Class II enhanced recovery and hydrocarbon storage wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and hydrocarbon storage wells. 144.22 Section 144.22 Protection of Environment ENVIRONMENTAL... of Underground Injection by Rule § 144.22 Existing Class II enhanced recovery and hydrocarbon storage wells. (a) An existing Class II enhanced recovery or hydrocarbon storage injection well is authorized by...

40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... kilograms) of production of each class II controlled substance used in processes resulting in their...) The quantity (in kilograms) of production of each class II controlled substance used in processes... processes resulting in their transformation or eventual destruction; (vi) A list of the quantities and names...

Effect of immunodepletion of MHC class II-positive cells from pancreatic islets on generation of cytotoxic T-lymphocytes in mixed islet-lymphocyte coculture.

PubMed

Stock, P G; Ascher, N L; Platt, J L; Kaufman, D B; Chen, S; Field, M J; Sutherland, D E

1989-01-01

In vitro manipulation of pancreatic islets to decrease islet immunogenicity before transplantation has largely been directed at eliminating the major histocompatibility complex (MHC) class II-positive passenger leukocytes from the islets. The mixed islet-lymphocyte coculture (MILC) system was used to quantitate the efficacy of immunodepletion of MHC class II-positive cells from pancreatic islets in terms of reducing immunogenicity. With these experiments we compared the in vitro immunogenicity of MHC class II-depleted islets with untreated islets. B10.BR (H-2k) islets were treated with anti-Iak alloserum followed by complement. This treatment successfully eliminated MHC class II-positive cells from the islets, as demonstrated by indirect immunofluorescence techniques. Depleted islets generated slightly lower amounts of allospecific cytotoxic T-lymphocyte (CTL) activity when exposed to C57BL/6 (H-2b) splenocytes in the MILC than untreated control islets. Although the amount of CTL generated by the depleted islets was slightly less than that generated by untreated islets, there was significant stimulation of CTL by the MHC class II-depleted islets. Therefore, the presence or absence of MHC class II cells within the islet is unlikely to be the decisive factor contributing to islet immunogenicity.

Skeletal effects in Angle Class II/1 patients treated with the functional regulator type II : Cephalometric and tensor analysis.

PubMed

Schulz, Simone; Koos, Bernd; Duske, Kathrin; Stahl, Franka

2016-11-01

The purpose of this work was to employ both cephalometric and tensor analysis in characterizing the skeletal changes experienced by patients with Angle Class II/1 malocclusion during functional orthodontic treatment with the functional regulator type II. A total of 23 patients with Class II/1 malocclusion based on lateral cephalograms obtained before and after treatment with the functional regulator type II were analyzed. Another 23 patients with Angle Class II/1 malocclusion who had not undergone treatment were included as controls. Our cephalometric data attest to significant therapeutic effects of the functional regulator type II on the skeletal mandibular system, including significant advancement of the mandible, increases in effective mandibular length with enhancement of the chin profile, and reduction of growth-related bite deepening. No treatment-related effects were observed at the cranial-base and midface levels. In addition, tensor analysis revealed significant stimulation of mandibular growth in sagittal directions, without indications of growth effects on the maxilla. Its growth-pattern findings differed from those of cephalometric analysis by indicating that the appliance did promote horizontal development, which supports the functional orthodontic treatment effect in Angle Class II/1 cases. Tensor analysis yielded additional insights into sagittal and vertical growth changes not identifiable by strictly cephalometric means. The functional regulator type II was an effective treatment modality for Angle Class II/1 malocclusion and influenced the skeletal development of these patients in favorable ways.

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.

PubMed

Gangaiah, Dharanesh; Spinola, Stanley M

2016-12-01

Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

Constitutive CD40L Expression on B Cells Prematurely Terminates Germinal Center Response and Leads to Augmented Plasma Cell Production in T Cell Areas

PubMed Central

Bolduc, Anna; Long, Eugene; Stapler, Dale; Cascalho, Marilia; Tsubata, Takeshi; Koni, Pandelakis A.; Shimoda, Michiko

2013-01-01

CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction. PMID:20505142

Type II Natural Killer T (NKT) Cells And Their Emerging Role In Health And Disease

PubMed Central

Dhodapkar, Madhav V.; Kumar, Vipin

2016-01-01

Natural killer T (NKT) cells recognize lipid antigens presented by a class I MHC-like molecule CD1d, a member of the CD1 family. While most of the initial studies on NKT cells focused on a subset with semi-invariant T cell receptor (TCR) termed iNKT cells, majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed as type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self lipid ligands, and share some properties with both iNKT as well as conventional T cells. Emerging body of evidence points to their role in the regulation of immunity to pathogens/tumors and in autoimmune/metabolic disorders. Improved understanding of the biology of these cells and the ability to manipulate their function may be of therapeutic benefit in diverse disease conditions. PMID:28115591

Effectiveness of laparoscopic Roux-en-Y gastric bypass on obese class I type 2 diabetes mellitus patients.

PubMed

Xu, Lu; Yin, Jun; Mikami, Dean J; Portenier, Dana D; Zhou, Xiaojun; Mao, Zhongqi

2015-01-01

Laparoscopic Roux-en-Y gastric bypass (LRYGB) can dramatically improve type 2 diabetes mellitus (T2D) in obese class II and III patients. There is increasing evidence that shows bariatric surgery can also ameliorate T2D in patients with BMI between 30 kg/m(2) and 35 kg/m(2) (obese class I). To compare the effectiveness of LRYGB on T2D in obese class I patients with that of obese class II and III T2D patients. University Hospital, China A prospective study was performed in the authors' center from March 2010 to July 2011. Forty-two consecutive obese patients were included in the study. Anthropometric and metabolism parameters were compared between obese class II and III patients and obese class I patients before and after LRYGB. No patients were lost to follow up. After 36 months, metabolic parameters significantly improved in both groups. Partial remission rates between the 2 groups at each time point (12 months, 24 months, and 36 months) were comparable. Obese class II and III patients had higher complete remission rates at 12 months and 24 months, but no difference was observed at 36 months. Both obese class II and III patients and obese class I T2D patients showed significant improvement in multiple parameters after LRYGB. Obese class II and III patients had a higher complete remission rate than obese class I patients. Standardized remission criteria are needed to make outcomes form different centers comparable. Large prospective studies are needed and long-term outcomes have to be observed to better evaluate effectiveness of LRYGB on obese class I T2D patients. Copyright © 2015 American Society for Bariatric Surgery. All rights reserved.

Pathognomonic features of Angle's Class II division 2 malocclusion: A comparative cephalometric and arch width study

PubMed Central

Prasad, Singamsetty E.R.V.; Indukuri, Ravikishore Reddy; Singh, Rupesh; Nooney, Anitha; Palagiri, Firoz Babu; Narayana, Veera

2014-01-01

Background: A thorough knowledge of the salient features of malocclusion helps the clinician in arriving at a proper diagnosis and treatment plan, and also to predict the prognosis, prior to the onset of treatment process. Among the four classes of Angle's classification of malocclusion, Class II division 2 occurs with the least frequency. There is still continuing debate in the literature whether the Class II division 2 patients ascribe the pathognomonic skeletal and dental features. Aim of the study: The aim of this study is to describe the unique features of Angle's Class II division 2 malocclusion to differentiate it from Angle's Class II division 1 malocclusion. Materials and Methods: A total of 582 pre-treatment records (study models and cephalograms), with the age of patients ranging from 15 to 22 years, were obtained from the hospital records of Vishnu Dental College, Bhimavaram and Geetam's Dental College, Visakhapatnam. Out of these, 11 pre-treatment records were excluded because of lack of clarity. In the rest of the sample, 283 were Class II division 1 and 288 were Class II division 2. The lateral cephalograms were analyzed by using digiceph and the arch width analysis was done based on the anatomical points described by Staley et al. and Sergl et al. Results: An intergroup evaluation was done by using unpaired Student's “t” test. The skeletal vertical parameters, dental parameters, and the maxillary arch width parameters revealed a statistically significant difference between the two groups of malocclusion. Conclusion: Angle's Class II division 2 malocclusion has a pronounced horizontal growth pattern with decreased lower anterior facial height, retroclined upper anteriors, and significantly increased maxillary arch width parameters. PMID:25558449

Recombinant plasmids for encoding restriction enzymes DpnI and DpnII of streptococcus pneumontae

DOEpatents

Lacks, Sanford A.

1990-01-01

Chromosomal DNA cassettes containing genes encoding either the DpnI or DpnII restriction endonucleases from Streptococcus pneumoniae are cloned into a streptococcal vector, pLS101. Large amounts of the restriction enzymes are produced by cells containing the multicopy plasmids, pLS202 and pLS207, and their derivatives pLS201, pLS211, pLS217, pLS251 and pLS252.

Recombinant plasmids for encoding restriction enzymes DpnI and DpnII of Streptococcus pneumontae

DOEpatents

Lacks, S.A.

1990-10-02

Chromosomal DNA cassettes containing genes encoding either the DpnI or DpnII restriction endonucleases from Streptococcus pneumoniae are cloned into a streptococcal vector, pLS101. Large amounts of the restriction enzymes are produced by cells containing the multicopy plasmids, pLS202 and pLS207, and their derivatives pLS201, pLS211, pLS217, pLS251 and pLS252. 9 figs.

Analysis of class II (hydrolytic) and class I (beta-lyase) apurinic/apyrimidinic endonucleases with a synthetic DNA substrate.

PubMed Central

Levin, J D; Demple, B

1990-01-01

We have developed simple and sensitive assays that distinguish the main classes of apurinic/apyrimidinic (AP) endonucleases: Class I enzymes that cleave on the 3' side of AP sites by beta-elimination, and Class II enzymes that cleave by hydrolysis on the 5' side. The distinction of the two types depends on the use of a synthetic DNA polymer that contains AP sites with 5'-[32P]phosphate residues. Using this approach, we now show directly that Escherichia coli endonuclease IV and human AP endonuclease are Class II enzymes, as inferred previously on the basis of indirect assays. The assay method does not exhibit significant interference by nonspecific nucleases or primary amines, which allows the ready determination of different AP endonuclease activities in crude cell extracts. In this way, we show that virtually all of the Class II AP endonuclease activity in E. coli can be accounted for by two enzymes: exonuclease III and endonuclease IV. In the yeast Saccharomyces cerevisiae, the Class II AP endonuclease activity is totally dependent on a single enzyme, the Apn1 protein, but there are probably multiple Class I enzymes. The versatility and ease of our approach should be useful for characterizing this important class of DNA repair enzymes in diverse systems. PMID:1698278

Somatic HLA Mutations Expose the Role of Class I-Mediated Autoimmunity in Aplastic Anemia and its Clonal Complications.

PubMed

Babushok, Daria V; Duke, Jamie L; Xie, Hongbo M; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J D; Kearns, Jane; Porter, David L; Podsakoff, Gregory M; Eisenlohr, Laurence C; Biegel, Jaclyn A; Chou, Stella T; Monos, Dimitrios S; Bessler, Monica; Olson, Timothy S

2017-10-10

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by Human Leukocyte Antigen (HLA)-restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole exome sequencing (WES), we recently identified two aAA patients with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the Major Histocompatibility Complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping we screened 66 aAA patients for somatic HLA class I loss. We found somatic HLA loss in eleven patients (17%), with thirteen loss-of-function mutations in HLA-A *33:03, HLA-A *68:01, HLA-B *14:02 and HLA-B *40:02 alleles. Three patients had more than one mutation targeting the same HLA allele. Interestingly, HLA-B *14:02 and HLA-B *40:02 were significantly overrepresented in aAA patients, compared to ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA, and establishes a novel link between aAA patients' immunogenetics and clonal evolution.

Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

PubMed Central

Duke, Jamie L.; Xie, Hongbo M.; Stanley, Natasha; Atienza, Jamie; Perdigones, Nieves; Nicholas, Peter; Ferriola, Deborah; Li, Yimei; Huang, Hugh; Ye, Wenda; Morrissette, Jennifer J. D.; Kearns, Jane; Porter, David L.; Podsakoff, Gregory M.; Eisenlohr, Laurence C.; Biegel, Jaclyn A.; Chou, Stella T.; Monos, Dimitrios S.; Bessler, Monica; Olson, Timothy S.

2017-01-01

Acquired aplastic anemia (aAA) is an acquired deficiency of early hematopoietic cells, characterized by inadequate blood production, and a predisposition to myelodysplastic syndrome (MDS) and leukemia. Although its exact pathogenesis is unknown, aAA is thought to be driven by human leukocyte antigen (HLA)–restricted T cell immunity, with earlier studies favoring HLA class II-mediated pathways. Using whole-exome sequencing (WES), we recently identified 2 patients with aAA with somatic mutations in HLA class I genes. We hypothesized that HLA class I mutations are pathognomonic for autoimmunity in aAA, but were previously underappreciated because the major histocompatibility complex (MHC) region is notoriously difficult to analyze by WES. Using a combination of targeted deep sequencing of HLA class I genes and single nucleotide polymorphism array (SNP-A) genotyping, we screened 66 patients with aAA for somatic HLA class I loss. We found somatic HLA loss in 11 patients (17%), with 13 loss-of-function mutations in HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, and HLA-B*40:02 alleles. Three patients had more than 1 mutation targeting the same HLA allele. Interestingly, HLA-B*14:02 and HLA-B*40:02 were significantly overrepresented in patients with aAA compared with ethnicity-matched controls. Patients who inherited the targeted HLA alleles, regardless of HLA mutation status, had a more severe disease course with more frequent clonal complications as assessed by WES, SNP-A, and metaphase cytogenetics, and more frequent secondary MDS. The finding of recurrent HLA class I mutations provides compelling evidence for a predominant HLA class I-driven autoimmunity in aAA and establishes a novel link between immunogenetics and clonal evolution of patients with aAA. PMID:28971166

40 CFR 147.2201 - State-administered program-Class II wells

Code of Federal Regulations, 2011 CFR

2011-07-01

... Application to Oil, Gas, and Geothermal Resource Operations, sections .051.02.02.000 to .051.02.02.080... wells 147.2201 Section 147.2201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Texas § 147.2201 State-administered program—Class II wells The UIC program for Class II wells in the...

38 CFR 17.162 - Eligibility for Class II dental treatment without rating action.

Code of Federal Regulations, 2011 CFR

2011-07-01

... dental treatment without rating action. 17.162 Section 17.162 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Dental Services § 17.162 Eligibility for Class II dental treatment without rating action. When an application has been made for class II dental treatment under § 17.161(b...

38 CFR 17.162 - Eligibility for Class II dental treatment without rating action.

Code of Federal Regulations, 2014 CFR

2014-07-01

... dental treatment without rating action. 17.162 Section 17.162 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Dental Services § 17.162 Eligibility for Class II dental treatment without rating action. When an application has been made for class II dental treatment under § 17.161(b...

38 CFR 17.162 - Eligibility for Class II dental treatment without rating action.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dental treatment without rating action. 17.162 Section 17.162 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Dental Services § 17.162 Eligibility for Class II dental treatment without rating action. When an application has been made for class II dental treatment under § 17.161(b...

38 CFR 17.162 - Eligibility for Class II dental treatment without rating action.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dental treatment without rating action. 17.162 Section 17.162 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Dental Services § 17.162 Eligibility for Class II dental treatment without rating action. When an application has been made for class II dental treatment under § 17.161(b...

38 CFR 17.162 - Eligibility for Class II dental treatment without rating action.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dental treatment without rating action. 17.162 Section 17.162 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Dental Services § 17.162 Eligibility for Class II dental treatment without rating action. When an application has been made for class II dental treatment under § 17.161(b...

40 CFR 147.2201 - State-administered program-Class II wells

Code of Federal Regulations, 2010 CFR

2010-07-01

... Application to Oil, Gas, and Geothermal Resource Operations, sections .051.02.02.000 to .051.02.02.080... wells 147.2201 Section 147.2201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Texas § 147.2201 State-administered program—Class II wells The UIC program for Class II wells in the...

The Effect of MHC Class II Transactivator on the Growth and Metastasis of Breast Tumors

DTIC Science & Technology

1999-06-01

F. Manca, and R. S. Accolla. 1998. HLA class II expression in uninducible hepatocarcinoma cells after transfection of AIR-1 gene product CIITA...Cestari, A. D’Agostino, ’ A M Megiovanni, F. Manca, and R. S. Accolla. 1998. HLA class II expression in uninducible hepatocarcinoma cells after

40 CFR 82.23 - Transfers of allowances of class II controlled substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... section. (2) Inter-pollutant transfers will be permitted at any time during the control period and during... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Transfers of allowances of class II... § 82.23 Transfers of allowances of class II controlled substances. (a) Inter-company transfers...

40 CFR 82.23 - Transfers of allowances of class II controlled substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... section. (2) Inter-pollutant transfers will be permitted at any time during the control period and during... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Transfers of allowances of class II... § 82.23 Transfers of allowances of class II controlled substances. (a) Inter-company transfers...

76 FR 16292 - Medical Devices; Immunology and Microbiology Devices; Classification of Ovarian Adnexal Mass...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-23

... test system into class II (special controls). The special control that will apply to these devices is the guidance document entitled ``Guidance for Industry and FDA Staff; Class II Special Controls... devices into class II (special controls) because special controls, in addition to general controls, will...

Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

PubMed Central

Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

2014-01-01

Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

Evolution of major histocompatibility complex class I and class II genes in the brown bear

PubMed Central

2012-01-01

Background Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia. PMID:23031405

Evolution of major histocompatibility complex class I and class II genes in the brown bear.

PubMed

Kuduk, Katarzyna; Babik, Wiesław; Bojarska, Katarzyna; Sliwińska, Ewa B; Kindberg, Jonas; Taberlet, Pierre; Swenson, Jon E; Radwan, Jacek

2012-10-02

Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

A vitellogenic-like carboxypeptidase expressed by human macrophages is localized in endoplasmic reticulum and membrane ruffles

PubMed Central

Harris, James; Schwinn, Nicole; Mahoney, James A; Lin, Hsi-Hsien; Shaw, Michael; Howard, Chris J; da Silva, Rosangela P; Gordon, Siamon

2006-01-01

Carboxypeptidase, vitellogenic-like (CPVL) is a serine carboxypeptidase of unknown function that was first characterized in human macrophages. Initial studies suggested that CPVL is largely restricted to the monocytic lineage, although it may also be expressed by cells outside the immune system. Here, we use a new monoclonal antibody to characterize the properties and localization of CPVL in human macrophages to elucidate a possible function for the protease. CPVL is up-regulated during the maturation of monocytes (MO) to macrophages, although the protein can be seen in both. In primary macrophages, CPVL is glycosylated with high mannose residues and colocalizes with markers for endoplasmic reticulum, while in MO it is more disperse and less clearly associated with endoplasmic reticulum. CPVL is highly expressed in lamellipodia and membrane ruffles, which also concentrate markers of the secretory pathway (MIP-1α and tumour necrosis factor-α) and major histocompatibility complex (MHC) class I and II molecules. CPVL can be seen on early latex bead and Candida albicans phagosomes, but it is not retained in the maturing phagosome, unlike MHC class I/II. CPVL has a mixed cytosolic and membrane-associated localization but is not detectable on the outer plasma membrane. We propose that CPVL may be involved in antigen processing, the secretory pathway and/or in actin remodelling and lamellipodium formation. PMID:16436111

Treatment effects of the Jasper Jumper and the Bionator associated with fixed appliances.

PubMed

Neves, Leniana Santos; Janson, Guilherme; Cançado, Rodrigo Hermont; de Lima, Karina Jerônimo Rodrigues Santiago; Fernandes, Thaís Maria Freire; Henriques, José Fernando Castanha

2014-01-01

The aim of this study was to evaluate the effects of Class II malocclusion treatment with the Jasper Jumper and the Bionator, associated with fixed appliances. The sample comprised 77 young individuals divided into 3 groups: Group 1 consisted of 25 patients treated with the Jasper Jumper appliance associated with fixed appliances for a mean period of 2.15 years; group 2 had 30 patients, treated with the Bionator and fixed appliances, for a mean treatment time of 3.92 years; and the control group included 22 subjects followed for a mean period of 2.13 years. The initial and final lateral cephalograms of the patients were evaluated. Intergroup comparison at the initial stage and of the treatment changes were performed by analysis of variance. Their effects consisted in a restrictive effect on the maxilla, a slight increase in anterior face height, retrusion and extrusion of the maxillary incisors, labial tipping and protrusion of the mandibular incisors in both groups and intrusion with the Jasper Jumper appliance, maxillary molar distalization with the Jasper Jumper, extrusion and mesialization of the mandibular molars, both appliances provided significant improvement of the maxillomandibular relationship, overjet, overbite and molar relationship. The effects of both appliances in class II malocclusion treatment are similar; however, treatment with the Jasper Jumper was shorter than with the Bionator.

Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

PubMed

Gelber, C; Gemmell, L; McAteer, D; Homola, M; Swain, P; Liu, A; Wilson, K J; Gefter, M

1997-03-01

Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.

[Trade-offs in the development of various dosage form (overview)].

PubMed

Uchida, Takahiro

2015-01-01

In this symposium we focused on trade-offs which might occur in the process of development of many types of formulation and corresponding dissolution methods. Firstly, we focused on a solubility-permeability trade-off in the case of micelle with surfactant or molecular complex with CyD. The micelle would be successful in increasing drug solubility, however it rather decreased permeability of model drug progesterone (Biopharmaceutics Classfication System (BCS) Class II) as an overall flux. Secondly in order to reduce bitterness of branched chain amino acid (BCAA), increasing particle sizes of each amino acid crystals involved in formulation was effective since the release rate of amino acid was restricted efficiently. Thirdly, in the case of injection of paclitaxel (BCS Class II)formulation, the drug was adsorbed to albumin. Thereby the risk of allergy was dramatically decreased compared to the case when non-ionic surfactant was used as an additive. Fourth, anticancer drug was incorporated into the internal (core) phase of an orally disintegrating tablet (ODT), this is also merit to avoid exposure of the drug to a nursing person or individual working person in manufacturing process. Fifth, the convenient syringe type kit pharmaceutical preparation for administration of total parenteral nutrition (TPN) to avoid incompatibility and its risk management effect was briefly discussed. Finally, the risk of an additive such as alcohol for a preterm infant was described.

Genetic variation of the MHC class II DRB genes in the Japanese weasel, Mustela itatsi, endemic to Japan, compared with the Siberian weasel, Mustela sibirica.

PubMed

Nishita, Y; Abramov, A V; Kosintsev, P A; Lin, L-K; Watanabe, S; Yamazaki, K; Kaneko, Y; Masuda, R

2015-12-01

Major histocompatibility complex (MHC) genes encode proteins that play a critical role in vertebrate immune system and are highly polymorphic. To further understand the molecular evolution of the MHC genes, we compared MHC class II DRB genes between the Japanese weasel (Mustela itatsi), a species endemic to Japan, and the Siberian weasel (Mustela sibirica), a closely related species on the continent. We sequenced a 242-bp region of DRB exon 2, which encodes antigen-binding sites (ABS), and found 24 alleles from 31 M. itatsi individuals and 17 alleles from 21 M. sibirica individuals, including broadly distributed, species-specific and/or geographically restricted alleles. Our results suggest that pathogen-driven balancing selection have acted to maintain the diversity in the DRB genes. For predicted ABS, nonsynonymous substitutions exceeded synonymous substitutions, also indicating positive selection, which was not seen at non-ABS. In a Bayesian phylogenetic tree, two M. sibirica DRB alleles were basal to the rest of the sequences from mustelid species and may represent ancestral alleles. Trans-species polymorphism was evident between many mustelid DRB alleles, especially between M. itatsi and M. sibirica. These two Mustela species divided about 1.7 million years ago, but still share many MHC alleles, indicative of their close phylogenetic relationship. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maxillary molar distalization with first class appliance

PubMed Central

Ramesh, Namitha; Palukunnu, Biswas; Ravindran, Nidhi; Nair, Preeti P

2014-01-01

Non-extraction treatment has gained popularity for corrections of mild-to-moderate class II malocclusion over the past few decades. The distalization of maxillary molars is of significant value for treatment of cases with minimal arch discrepancy and mild class II molar relation associated with a normal mandibular arch and acceptable profile. This paper describes our experience with a 16-year-old female patient who reported with irregularly placed upper front teeth and unpleasant smile. The patient was diagnosed to have angles class II malocclusion with moderate maxillary anterior crowding, deep bite of 4 mm on a skeletal class II base with an orthognathic maxilla and retrognathic mandible and normal growth pattern. She presented an ideal profile and so molar distalization was planned with the first-class appliance. Molars were distalised by 8 mm on the right and left quadrants and class I molar relation achieved within 4 months. The space gained was utilised effectively to align the arch and establish a class I molar and canine relation. PMID:24577171

Distalization of maxillary arch and correction of Class II with mini-implants: A report of two cases

PubMed Central

Tekale, Pawankumar Dnyandeo; Vakil, Ketan K.; Vakil, Jeegar K.; Gore, Ketan A.

2015-01-01

This article reports the successful use of mini-screws in the maxilla to treat two patients of age 21-year and 17-year-old girls. Both the patients had a skeletal Class II malocclusion with protrusive maxillary teeth and angels Class II mal-occlusion. Temporary anchorage devices (TADs) in the posterior dental region between maxillary second premolar and maxillary first molar teeth on both sides were used as anchorage for the retraction and intrusion of her maxillary anterior teeth. Those appliances, combined with a compensatory curved maxillary archwire, eliminated spacing, deep bite, forwardly placed and proclined upper front teeth and the protrusive profile, corrected the molar relationship from Class II to Class I. With no extra TADs in the anterior region for intrusion, the treatment was workable and simple. The patient received a satisfactory occlusion and an attractive smile. This technique requires minimal compliance and is particularly useful for correcting Class II patients with protrusive maxillary front teeth and dental deep bite. PMID:26097360

Comparison of inducible nitric oxide synthase expression in the brains of Listeria monocytogenes-infected cattle, sheep, and goats and in macrophages stimulated in vitro.

PubMed

Jungi, T W; Pfister, H; Sager, H; Fatzer, R; Vandevelde, M; Zurbriggen, A

1997-12-01

The expression of inducible nitric oxide synthase (iNOS) was studied in the brains of cattle, sheep, and goat that succumbed to a natural infection with Listeria monocytogenes. The lesions in infected brains are characterized by microabscesses, perivascular cuffs, gliosis, glial nodules, and large areas of malacia. Using immunocytochemistry, we detected bacteria in microabscesses, particularly in sheep and goats, and in areas without signs of inflammation, but not in perivascular infiltrates. iNOS was expressed by macrophage (Mphi)-type cells of microabscesses and glial nodules but rarely by Mphi in areas of malacia, as determined by immunohistochemistry with iNOS-specific antibodies. iNOS was not detected in perivascular cuffs. Major histocompatibility complex class II molecules (MHC-II), another marker of cell activation, showed a different pattern of distribution. Perivascular cuffs contained high numbers of MHC-II-positive cells, including some with Mphi characteristics. Microabscesses in sheep and goats showed low expression of MHC-II, particularly in iNOS-expressing cells. In cattle, the expression of markers for activated or recruited phagocytes, the calcium-binding proteins S100A8 and S100A9 (formerly called MRP-8 and MRP-14, respectively), was largely restricted to cells showing weak or undetectable iNOS expression; iNOS-positive Mphi showed a low expression of S100A8 and S100A9. Thus, iNOS is expressed by a restricted subset of Mphi in listeric encephalitis. In cultured sheep and goat Mphi, a low proportion of cells expressed iNOS upon activation by L. monocytogenes and gamma interferon, resulting in nitrite generation at least 1 order of magnitude lower than that in similarly treated cattle Mphi. Since these species differences were much less obvious in vivo, it appears that the well-known species variation in iNOS expression by Mphi could reflect an in vitro phenomenon.

47 CFR 13.9 - Eligibility and application for new license or endorsement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Radar Endorsement, Six Months Service Endorsement, GMDSS Radio Operator's License, Restricted GMDSS... Operator License, Marine Radio Operator Permit, First Class Radiotelegraph Operator's Certificate, Second... Restricted Radiotelephone Operator Permit or a Restricted Radiotelephone Operator Permit-Limited Use must be...

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

25 CFR 547.7 - What are the minimum technical hardware standards applicable to Class II gaming systems?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.7 What are the minimum technical hardware standards applicable to Class II... the game, and are specially manufactured or proprietary and not off-the-shelf, shall display a unique... outcome or integrity of any game, progressive award, financial instrument, cashless transaction, voucher...

40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... transformation; (v) The date on which the class II controlled substances were imported; (vi) The port of entry.... Customs entry form; (xiv) Dated records documenting the sale or transfer of class II controlled substances... source facility; (vii) The U.S. port of entry for the import, the expected date of shipment and the...

40 CFR 82.24 - Recordkeeping and reporting requirements for class II controlled substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... transformation; (v) The date on which the class II controlled substances were imported; (vi) The port of entry.... Customs entry form; (xiv) Dated records documenting the sale or transfer of class II controlled substances... source facility; (vii) The U.S. port of entry for the import, the expected date of shipment and the...

25 CFR 547.6 - What are the minimum technical standards for enrolling and enabling Class II gaming system...

Code of Federal Regulations, 2010 CFR

2010-04-01

... and enabling Class II gaming system components? 547.6 Section 547.6 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR HUMAN SERVICES MINIMUM TECHNICAL STANDARDS FOR GAMING EQUIPMENT USED WITH THE PLAY OF CLASS II GAMES § 547.6 What are the minimum technical standards for enrolling and...

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Class II Controlled Substances a B Appendix B to Subpart A of Part 82 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled...

40 CFR 82.17 - Apportionment of baseline production allowances for class II controlled substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... allowances for class II controlled substances. 82.17 Section 82.17 Protection of Environment ENVIRONMENTAL... Consumption Controls § 82.17 Apportionment of baseline production allowances for class II controlled... 1,759,681 MDA Manufacturing HCFC-22 2,383,835 Solvay Solexis HCFC-142b 6,541,764 [ 74 FR 66446, Dec...

40 CFR 144.21 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... recovery and hydrocarbon storage) and III wells. 144.21 Section 144.21 Protection of Environment... hydrocarbon storage) and III wells. (a) An existing Class I, II (except enhanced recovery and hydrocarbon... decision; or (9) For Class II wells (except enhanced recovery and hydrocarbon storage), five years after...

40 CFR 144.21 - Existing Class I, II (except enhanced recovery and hydrocarbon storage) and III wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... recovery and hydrocarbon storage) and III wells. 144.21 Section 144.21 Protection of Environment... hydrocarbon storage) and III wells. (a) An existing Class I, II (except enhanced recovery and hydrocarbon... decision; or (9) For Class II wells (except enhanced recovery and hydrocarbon storage), five years after...

77 FR 24978 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Leases, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...

76 FR 14686 - Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-17

... Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Proposed Class II Reinstatement of Terminated Oil and Gas Lease, Utah. SUMMARY: In accordance with Title IV of the Federal Oil and Gas Royalty Management Act (Pub. L. 97-451...

76 FR 20840 - Medical Devices; General and Plastic Surgery Devices; Classification of the Low Level Laser...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

... into class II (special controls). The special control(s) that will apply to the device is entitled ``Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use.'' The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety...

Assessment of the changes in quality of life of patients with class II and III deformities during and after orthodontic-surgical treatment.

PubMed

Baherimoghaddam, T; Tabrizi, R; Naseri, N; Pouzesh, A; Oshagh, M; Torkan, S

2016-04-01

The aim of this longitudinal study was to assess and compare the oral health-related quality of life (OHRQoL) of patients with class II and III deformities during and after orthodontic-surgical treatment. Thirty class III and 28 class II patients were evaluated at baseline (T0), just prior to surgery (T1), at 6 months after surgery (T2), and at 12 months after debonding (T3). OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). Friedman two-way analysis of variance and the Wilcoxon signed-rank test were performed to compare the relative changes in OHRQoL during treatment. Significant changes in the overall OHIP-14 scores were observed during and after orthodontic-surgical treatment in both groups. During the pre-surgical stage, psychological discomfort and psychological disability decreased in class III patients, and class II patients experienced a significant deterioration in psychological discomfort during the same period. Six months after surgery, patients in both groups showed improvements in psychological discomfort, social disability, and handicap. Physical disability and functional limitation showed further improvement at 12 months after debonding in class II patients. This study reaffirms that orthodontic-surgical treatment has a significant effect on the OHRQoL of class III and class II patients. Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens

PubMed Central

Xing, Dongxia; Li, Sufang; Robinson, Simon N.; Yang, Hong; Steiner, David; Komanduri, Krishna V.; Shpall, Elizabeth J.

2009-01-01

In the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must interpret a complex array of stimuli, many of which are poorly understood. Here we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous phenomena triggered by the loading of DCs with antigenically matched major histocompatibility complex (MHC) class I and class II determinants, that is, class I and II peptide epitopes exhibiting significant amino acid sequence overlap (such as would be physiologically present during infectious processes requiring Th-1 immunity for clearance). Data were derived from 13 independent antigenic models including whole-cell systems, single-protein systems, and 3 different pairs of overlapping class I and II binding epitopes. Once loaded with matched class I and II antigens, these “Th-1 DCs” exhibited differential cytokine secretion and surface marker expression, a distinct transcriptional signature, and acquired the ability to enhance generation of CD8+ T lymphocytes. Mechanistically, tRNA-synthetases were implicated as components of a putative sensor complex involved in the comparison of class I and II epitopes. These data provide rigorous conceptual explanations for the process of Th-1 polarization and the antigenic specificity of cognate T-cell help, enhance the understanding of Th-1 responses, and should contribute to the formulation of more effective vaccination strategies. PMID:19171878

DMA and DMB are the only genes in the class II region of the human MHC needed for class II-associated antigen processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ceman, S.; Rudersdorf, R.A.; Petersen, J.M.

1995-03-15

Previous studies have shown that homozygous mutations between the LMP2 and DNA loci in the human MHC cause class II molecules to be abnormally conformed and unstable in the presence of SDS at low temperature, and impede class II-associated Ag processing and presentation. These abnormalities result from impaired ability to form intracellular class II/peptide complexes that predominate in normal cells. We show in this work that this defect results from deficient expression of either the DMA or the DMB gene. Human B-LCL.174 (DR3) cells, which have a deletion of all known expressible genes in the class II region, express transgene-encodedmore » HLA-DR3, but have the abnormalities. Transfer of cosmid HA14, which contains the DMA and DMB genes, into .174 (DR3) cells restored normal DR3 conformation, stability in 0.4% SDS at 0{degrees}, and ability to process and present tetanus toxoid, but only when both DMA and DMB mRNAs were present. The requirement for both genetic expressions in engendering normal phenotypes was confirmed by transferring the cloned genes into .174 (DR3) cells separately or together. Because normal phenotypes were fully restored in transferent cells expressing DMA plus DMB, other genes in the {approximately} 1-mb homozygous class II region deletion in .174 (DR3) cells either do not participate in or are dispensable for apparently normal production of intracellular class II/peptide complexes. The properties of DM-deficient EBV-transformed B lymphoblastoid cell lines (LCLs) suggest ways of identifying humans in whom DM deficiency contributes to congenital immunodeficiency and malignancy. 67 refs., 5 figs., 1 tab.« less

A retrospective study of Class II mixed-dentition treatment.

PubMed

Oh, Heesoo; Baumrind, Sheldon; Korn, Edward L; Dugoni, Steven; Boero, Roger; Aubert, Maryse; Boyd, Robert

2017-01-01

To consider the effectiveness of early treatment using one mixed-dentition approach to the correction of moderate and severe Class II malocclusions. Three groups of Class II subjects were included in this retrospective study: an early treatment (EarlyTx) group that first presented at age 7 to 9.5 years (n = 54), a late treatment (LateTx) group whose first orthodontic visit occurred between ages 12 and 15 (n = 58), and an untreated Class II (UnTx) group to assess the pretreatment comparability of the two treated groups (n = 51). Thirteen conventional cephalometric measurements were reported for each group and Class II molar severity was measured on the study casts of the EarlyTx and LateTx groups. Successful Class II correction was observed in approximately three quarters of both the EarlyTx group and the LateTx group at the end of treatment. EarlyTx patients had fewer permanent teeth extracted than did the LateTx patients (5.6% vs 37.9%, P < .001) and spent less time in full-bonded appliance therapy in the permanent dentition than did LateTx patients (1.7 ± 0.8 vs 2.6 ± 0.7years, P < .001). When supervision time is included, the EarlyTx group had longer total treatment time and averaged more visits than did the LateTx group (53.1 ± 18. 8 vs 33.7 ± 8.3, P < .0001). Fifty-five percent of the LateTx extraction cases involved removal of the maxillary first premolars only and were finished in a Class II molar relationship. EarlyTx comprehensive mixed-dentition treatment was an effective modality for early correction of Class II malocclusions.

Selection and Trans-Species Polymorphism of Major Histocompatibility Complex Class II Genes in the Order Crocodylia

PubMed Central

Jaratlerdsiri, Weerachai; Isberg, Sally R.; Higgins, Damien P.; Miles, Lee G.; Gongora, Jaime

2014-01-01

Major Histocompatibility Complex (MHC) class II genes encode for molecules that aid in the presentation of antigens to helper T cells. MHC characterisation within and between major vertebrate taxa has shed light on the evolutionary mechanisms shaping the diversity within this genomic region, though little characterisation has been performed within the Order Crocodylia. Here we investigate the extent and effect of selective pressures and trans-species polymorphism on MHC class II α and β evolution among 20 extant species of Crocodylia. Selection detection analyses showed that diversifying selection influenced MHC class II β diversity, whilst diversity within MHC class II α is the result of strong purifying selection. Comparison of translated sequences between species revealed the presence of twelve trans-species polymorphisms, some of which appear to be specific to the genera Crocodylus and Caiman. Phylogenetic reconstruction clustered MHC class II α sequences into two major clades representing the families Crocodilidae and Alligatoridae. However, no further subdivision within these clades was evident and, based on the observation that most MHC class II α sequences shared the same trans-species polymorphisms, it is possible that they correspond to the same gene lineage across species. In contrast, phylogenetic analyses of MHC class II β sequences showed a mixture of subclades containing sequences from Crocodilidae and/or Alligatoridae, illustrating orthologous relationships among those genes. Interestingly, two of the subclades containing sequences from both Crocodilidae and Alligatoridae shared specific trans-species polymorphisms, suggesting that they may belong to ancient lineages pre-dating the divergence of these two families from the common ancestor 85–90 million years ago. The results presented herein provide an immunogenetic resource that may be used to further assess MHC diversity and functionality in Crocodylia. PMID:24503938

Changes in Cranial Base Morphology in Class I and Class II Division 1 Malocclusions

PubMed Central

Agarwal, Anirudh; Pandey, Harsh; Bajaj, Kamal; Pandey, Lavesh

2013-01-01

Introduction: The cranial base plays a key role in craniofacial growth; it helps to integrate spatially and functionally different patterns of growth in various adjoining regions of the skull such as components of the brain, the nasal and oral cavity and the pharynx. The aim of this study was to evaluate the difference in cranial base flexure between skeletal and dental Class I and Class II division 1. Materials & Methods: Lateral cephalometric radiograph, of Class I and Class II with an average growth pattern were analyzed and compared. A total of 103 patients having class I (n=52) and class II (n=51) malocclusion, were taken from Department of Orthodontics, Rajasthan Dental College & Hospital, Jaipur. Cranial base angle (N-S-Ar) and ANB were measured on pre treatment lateral cephalograms. Results: In this study cranial base angle did not show statistically significant difference between the two groups studied. Conclusion: In the assessment of orthodontic problems involving anteroposterior malrelationships of the jaws, the problem is usually the result of size, form and position of the jaw. The present study failed to find any differences in cranial base angle between sagittal malocclusions. How to cite this article: Agarwal A, Pandey H, Bajaj K, Pandey L. Changes in Cranial Base Morphology in Class I and Class II Division 1 Malocclusion. J Int Oral Health 2013; 5(1):39-42. PMID:24155576

Investigation into the Emerging Role of the Basic Amino Acid L-Lysine in Enhancing Solubility and Permeability of BCS Class II and BCS Class IV Drugs.

PubMed

Abdelkader, Hamdy; Fathalla, Zeinab

2018-06-18

The search for a simple and scalable approach that can improve the two key biopharmaceutical processes (solubility and permeability) for BCS Class II and BCS Class IV has still been unmet need. In this study, L-lysine was investigated as a potential excipient to tackle problems with solubility and permeability. Bendazac (Class II); quercetin and rutin (Class IV) were employed. Drugs-lysine complexes in 1:1 M ratios were prepared by co-precipitation and co-grinding; characterized for solubility, partition coefficient, DSC, FTIR, SEM, dissolution rate and permeability. Chemical stability of quercetin-lysine and rutin-lysine was studied by assessing antioxidant capacity using Trolox and CUPRAC assays. Drugs-lysine salt/complexes were confirmed. Solubility enhancement factors ranged from 68- to 433-fold increases and dissolution rates were also significantly enhanced by up to 6-times, compared with drugs alone. With the exception of rutin-lysine, P app for bendazac-lysine and quercetin-lysine enhanced by 2.3- to 4-fold. P app for quercetin (Class IV) benefited more than bendazac (Class II) when complexed with lysine. This study warrants the use of L-lysine as a promising excipient for enhanced solubility and permeability of Class II and Class IV, providing that the solubility of the drug is ensured at 'the door step' of absorption sites.

Growth in individuals with Majewski osteodysplastic primordial dwarfism type II caused by pericentrin mutations.

PubMed

Bober, Michael B; Niiler, Tim; Duker, Angela L; Murray, Jennie E; Ketterer, Tara; Harley, Margaret E; Alvi, Sabah; Flora, Christina; Rustad, Cecilie; Bongers, Ernie M H F; Bicknell, Louise S; Wise, Carol; Jackson, Andrew P

2012-11-01

Microcephalic primordial dwarfism (MPD) is a class of disorders characterized by intrauterine growth restriction (IUGR), impaired postnatal growth and microcephaly. Majewski osteodysplastic primordial dwarfism type II (MOPD II) is one of the more common conditions within this group. MOPD II is caused by truncating mutations in pericentrin (PCNT) and is inherited in an autosomal recessive manner. Detailed growth curves for length, weight, and OFC are presented here and derived from retrospective data from 26 individuals with MOPD II confirmed by molecular or functional studies. Severe pre- and postnatal growth failure is evident in MOPD II patients. The length, weight, and OFC at term (when corrected for gestational age) were -7.0, -3.9, and -4.6 standard deviation (SD) below the population mean and equivalent to the 50th centile of a 28-29-, 31-32-, and 30-31-week neonate, respectively. While at skeletal maturity, the height, weight, and OFC were -10.3, -14.3, and -8.5 SD below the population mean and equivalent to the size of 3-year 10- to 11-month-old, a 5-year 2- to 3-month-old, and 5- to 6-month-old, respectively. During childhood, MOPD II patients grow with slowed, but fairly constant growth velocities and show no evidence of any pubertal growth spurt. Treatment with human growth hormone (n = 11) did not lead to any significant improvement in final stature. The growth charts presented here will be of assistance with diagnosis and management of MOPD II, and should have particular utility in nutritional management of MOPD II during infancy. Copyright © 2012 Wiley Periodicals, Inc.

MHC class II is an important genetic risk factor for canine systemic lupus erythematosus (SLE)-related disease: implications for reproductive success.

PubMed

Wilbe, M; Andersson, G

2012-01-01

Major histocompatibility complex (MHC) class II genes are important genetic risk factors for development of immune-mediated diseases in mammals. Recently, the dog (Canis lupus familiaris) has emerged as a useful model organism to identify critical MHC class II genotypes that contribute to development of these diseases. Therefore, a study aimed to evaluate a potential genetic association between the dog leukocyte antigen (DLA) class II region and an immune-mediated disease complex in dogs of the Nova Scotia duck tolling retriever breed was performed. We show that DLA is one of several genetic risk factors for this disease complex and that homozygosity of the risk haplotype is disadvantageous. Importantly, the disease is complex and has many genetic risk factors and therefore we cannot provide recommendations for breeders exclusively on the basis of genetic testing for DLA class II genotype. © 2012 Blackwell Verlag GmbH.

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

PubMed

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

2012-10-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

PubMed Central

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

2012-01-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies

PubMed Central

Gangaiah, Dharanesh

2016-01-01

Background Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. Methodology/Principal Findings We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. Conclusions/Significance CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities. PMID:28027326

Neurobehavioral toxicology of pyrethroid insecticides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crofton, K.M.

1986-01-01

Pyrethroid insecticides are classified as either Type I or Type II based upon in vivo toxic signs, and neurophysiological and biochemical data. Both axonal sodium channels and the ..gamma..-aminobutyric acid (GABA) receptor complex have been proposed as the major site of action of the Type II pyrethroids. This investigation characterized the behavior and biochemical effects of low dosages of pyrethroids in rats. Type I and II pyrethroids were tested for effects on figure-eight maze activity and the acoustic startle response (ASR). All compounds decreased figure-eight maze activity. Interactions of Type I and II pyrethroids with the three major binding sitesmore » on the GABA complex were determined in vivo. Radioligand binding experiments assessed in vitro interactions of pyrethroids with the three major GABA-complex binding sites. None of the pyrethroids competed for (/sup 3/H)-muscimol or (/sup 3/H)-flunitrazepam binding. Only Type II pyrethroids inhibited binding of (/sup 35/S)-t-butylbicyclophosphorothionate (TBPS) in cortical synaptosome preparations with K/sub i/ values of 5 to 10 ..mu..M. The (/sup 35/S)-TBPS data implicate the TBPS/picrotoxinin binding site in the mechanism of Type II pyrethroid toxicity. The results of these experiments support the classification of pyrethroids into two classes, and demonstrate the utility of the figure-eight maze and the ASR in studies to elucidate neurotoxic mechanisms. The interaction of the Type II pyrethroids is probably restricted to the TBPS/picrotoxinin binding domain on the GABA complex as shown by both the in vivo and in vitro studies.« less

77 FR 36951 - Gastroenterology-Urology Devices; Reclassification of Implanted Blood Access Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... into class II (special controls). FDA is proposing this reclassification on its own initiative based on... categories (classes) of devices, reflecting the regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three categories of devices are class I (general controls), class II...

78 FR 5327 - Medical Devices; Ophthalmic Devices; Classification of the Scleral Plug

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... Agency) is proposing to classify the scleral plug into class II (special controls), and proposing to... controls needed to provide reasonable assurance of their safety and effectiveness. The three categories of devices are class I (general controls), class II (special controls), and class III (premarket approval...

Association of maternal anti-HLA class II antibodies with protection from allergy in offspring.

PubMed

Jones, M; Jeal, H; Harris, J M; Smith, J D; Rose, M L; Taylor, A N; Cullinan, P

2013-09-01

Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years. Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age. Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order. This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2010 CFR

2010-04-01

... OF CLASS II GAMES § 547.12 What are the minimum technical standards for downloading on a Class II... software, files, data, and prize schedules. (2) Downloads of software, games, prize schedules, or other... performed in a manner that will not affect game play. (5) Downloads shall not affect the integrity of...

25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2011 CFR

2011-04-01

... OF CLASS II GAMES § 547.12 What are the minimum technical standards for downloading on a Class II... software, files, data, and prize schedules. (2) Downloads of software, games, prize schedules, or other... performed in a manner that will not affect game play. (5) Downloads shall not affect the integrity of...

25 CFR 547.12 - What are the minimum technical standards for downloading on a Class II gaming system?

Code of Federal Regulations, 2012 CFR

2012-04-01

... OF CLASS II GAMES § 547.12 What are the minimum technical standards for downloading on a Class II... software, files, data, and prize schedules. (2) Downloads of software, games, prize schedules, or other... performed in a manner that will not affect game play. (5) Downloads shall not affect the integrity of...

40 CFR 147.650 - State-administrative program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Idaho § 147.650 State-administrative program—Class I, II, III, IV, and V wells. The UIC program for Class I, II, III, IV, and V wells in the State of Idaho, other than those on Indian lands, is the program administered by the Idaho Department of Water Resources, approved by EPA pursuant to...

40 CFR Appendix B to Subpart A of... - Class II Controlled Substances a

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 17 2010-07-01 2010-07-01 false Class II Controlled Substances a B..., Subpt. A, App. B Appendix B to Subpart A of Part 82—Class II Controlled Substances a Controlled... the highest ODP, and the lower value is the estimate of the ODP of the isomer with the lowest ODP...

Poster - Thur Eve - 07: CNSC Update: "What's New in Class II".

PubMed

Heimann, M

2012-07-01

The Accelerators and Class II Facilities Division (ACFD) of the Canadian Nuclear Safety Commission (CNSC), is responsible for the oversight of radiotherapy facilities containing Class II prescribed equipment in Canada. This poster will highlight a number of new initiatives that the CNSC has implemented recently that have an impact on radiotherapy facility licensees. The presentation will discuss the recent policy decision to regulate particle accelerators of above 1 MeV. Challenges and progress with respect to the implementation of the policy will be presented. Other initiatives which will be described include: • The new ACFD webspace on the CNSC website, with direct links to relevant information on licensing, compliance and Class II prescribed equipment • The improved structure of the Appendix of Licence Documents that is part of every Class II licence • Updated licence application guides • Changes to Annual Compliance reporting requirements and progress on the ACR-Online initiative • Changes to some regulatory expectations related to medical accelerator facilities • Consolidation of Class II facility licences The poster will also include other initiatives that may be of particular interest to COMP membership. © 2012 American Association of Physicists in Medicine.

Class II G Protein-Coupled Receptors and Their Ligands in Neuronal Function and Protection

PubMed Central

Martin, Bronwen; de Maturana, Rakel Lopez; Brenneman, Randall; Walent, Tom; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class II GPCRs which couples predominantly to the Gs–adenylate cyclase–cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class II GPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class II GPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class II GPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders. PMID:16052036

49 CFR 1150.45 - Procedures and relevant dates-transactions under section 10902 that involve creation of Class I...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Procedures and relevant dates-transactions under section 10902 that involve creation of Class I or Class II rail carriers. 1150.45 Section 1150.45... dates—transactions under section 10902 that involve creation of Class I or Class II rail carriers. (a...

49 CFR 1150.45 - Procedures and relevant dates-transactions under section 10902 that involve creation of Class I...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 8 2014-10-01 2014-10-01 false Procedures and relevant dates-transactions under section 10902 that involve creation of Class I or Class II rail carriers. 1150.45 Section 1150.45... dates—transactions under section 10902 that involve creation of Class I or Class II rail carriers. (a...

49 CFR 1150.45 - Procedures and relevant dates-transactions under section 10902 that involve creation of Class I...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Procedures and relevant dates-transactions under section 10902 that involve creation of Class I or Class II rail carriers. 1150.45 Section 1150.45... dates—transactions under section 10902 that involve creation of Class I or Class II rail carriers. (a...

49 CFR 1150.45 - Procedures and relevant dates-transactions under section 10902 that involve creation of Class I...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 8 2013-10-01 2013-10-01 false Procedures and relevant dates-transactions under section 10902 that involve creation of Class I or Class II rail carriers. 1150.45 Section 1150.45... dates—transactions under section 10902 that involve creation of Class I or Class II rail carriers. (a...

49 CFR 1150.45 - Procedures and relevant dates-transactions under section 10902 that involve creation of Class I...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Procedures and relevant dates-transactions under section 10902 that involve creation of Class I or Class II rail carriers. 1150.45 Section 1150.45... dates—transactions under section 10902 that involve creation of Class I or Class II rail carriers. (a...

Prevalence of class-I, class-II and class-III obesity in Australian adults between 1995 and 2011-12.

PubMed

Keating, Catherine; Backholer, Kathryn; Gearon, Emma; Stevenson, Christopher; Swinburn, Boyd; Moodie, Marj; Carter, Rob; Peeters, Anna

2015-01-01

To compare the prevalence of class-I, II and III obesity in Australian adults between 1995, 2007-08 and 2011-12. Prevalence data for adults (aged 18+ years) were sourced from customised data from the nationally representative National Nutrition Survey (1995), the National Health Survey (2007-08), and the Australian Health Survey (2011-12) conducted by the Australian Bureau of Statistics. Obesity classifications were based on measured height and weight (class-I body mass index: 30.0-34.9 kg/m(2), class-II: 35.0-39.9 kg/m(2) and class-III: ≥ 40.0 kg/m(2)). Severe obesity was defined as class-II or class-III obesity. Between 1995 and 2011-12, the prevalence of obesity (all classes combined) increased from 19.1% to 27.2%. During this 17 year period, relative increases in class I, II and III obesity were 1.3, 1.7 and 2.2-fold respectively. In 2011-12, the prevalence of class I, II and III obesity was 19.4, 5.9 and 2.0 per cent respectively in men, and 16.1, 6.9 and 4.2 per cent respectively in women. One in every ten people was severely obese, increasing from one in twenty in 1995, and women were disproportionally represented in this population. Obesity prevalence increased with increasing levels of area-level socioeconomic disadvantage, particularly for the more severely obese classes. Severe obesity affected 6.2% and 13.4% in the least and most disadvantaged quintiles respectively. Over the last two decades, there have been substantial increases in the prevalence of obesity, particularly the more severe levels of obesity. This study highlights high risk groups who warrant targeted weight gain prevention interventions. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Predominant typologies of psychopathology in the United States: a latent class analysis.

PubMed

El-Gabalawy, Renée; Tsai, Jack; Harpaz-Rotem, Ilan; Hoff, Rani; Sareen, Jitender; Pietrzak, Robert H

2013-11-01

Latent class analysis (LCA) offers a parsimonious way of classifying common typologies of psychiatric comorbidity. We used LCA to identify the nature and correlates of predominant typologies of Axis I and II disorders in a large and comprehensive population-based sample of U.S. adults. We analyzed data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (2004-2005; n = 34,653), a population-based sample of U.S. adults. We derived latent classes based on all assessed Axis I and II disorders and examined the relationship between the identified Axis I classes and lifetime psychiatric disorders and suicide attempts, and physical and mental health-related quality of life. A four-class solution was optimal in characterizing predominant typologies of both Axis I and II disorders. For Axis I disorders, these included low psychopathology (n = 28,935, 84.0%), internalizing (n = 3693, 9.9%), externalizing (n = 1426, 4.5%), and high psychopathology (n = 599, 1.6%) classes. For Axis II disorders, these included no/low personality disorders (n = 31,265, 90.9%), obsessive/paranoid (n = 1635, 4.6%), borderline/dysregulated (n = 1319, 3.4%), and highly comorbid (n = 434, 1.1%) classes. Compared to the low psychopathology class, all other Axis I classes had significantly increased odds of mental disorders, elevated Axis II classes, suicide attempts and poorer quality of life, with the high psychopathology class having the overall highest rates of these correlates, with the exception of substance use disorders. Compared to the low psychopathology class, the internalizing and externalizing classes had increased rates of mood and anxiety disorders, and substance use disorders, respectively. Axis I and II psychopathology among U.S. adults may be best represented by four predominant typologies. Characterizing co-occurring patterns of psychopathology using person-based typologies represents a higher-order classification system that may be useful in clinical and research settings. Published by Elsevier Ltd.

A yeast-based assay identifies drugs that interfere with immune evasion of the Epstein-Barr virus.

PubMed

Voisset, Cécile; Daskalogianni, Chrysoula; Contesse, Marie-Astrid; Mazars, Anne; Arbach, Hratch; Le Cann, Marie; Soubigou, Flavie; Apcher, Sébastien; Fåhraeus, Robin; Blondel, Marc

2014-04-01

Epstein-Barr virus (EBV) is tightly associated with certain human cancers, but there is as yet no specific treatment against EBV-related diseases. The EBV-encoded EBNA1 protein is essential to maintain viral episomes and for viral persistence. As such, EBNA1 is expressed in all EBV-infected cells, and is highly antigenic. All infected individuals, including individuals with cancer, have CD8(+) T cells directed towards EBNA1 epitopes, yet the immune system fails to detect and destroy cells harboring the virus. EBV immune evasion depends on the capacity of the Gly-Ala repeat (GAr) domain of EBNA1 to inhibit the translation of its own mRNA in cis, thereby limiting the production of EBNA1-derived antigenic peptides presented by the major histocompatibility complex (MHC) class I pathway. Here we establish a yeast-based assay for monitoring GAr-dependent inhibition of translation. Using this assay we identify doxorubicin (DXR) as a compound that specifically interferes with the GAr effect on translation in yeast. DXR targets the topoisomerase-II-DNA complexes and thereby causes genomic damage. We show, however, that the genotoxic effect of DXR and various analogs thereof is uncoupled from the effect on GAr-mediated translation control. This is further supported by the observation that etoposide and teniposide, representing another class of topoisomerase-II-DNA targeting drugs, have no effect on GAr-mediated translation control. DXR and active analogs stimulate, in a GAr-dependent manner, EBNA1 expression in mammalian cells and overcome GAr-dependent restriction of MHC class I antigen presentation. These results validate our approach as an effective high-throughput screening assay to identify drugs that interfere with EBV immune evasion and, thus, constitute candidates for treating EBV-related diseases, in particular EBV-associated cancers.

Early recycling compartment trafficking of CD1a is essential for its intersection and presentation of lipid antigens.

PubMed

Cernadas, Manuela; Cavallari, Marco; Watts, Gerald; Mori, Lucia; De Libero, Gennaro; Brenner, Michael B

2010-02-01

A major step in understanding differences in the nature of Ag presentation was the realization that MHC class I samples peptides transported to the endoplasmic reticulum from the cytosol, whereas MHC class II samples peptides from lysosomes. In contrast to MHC class I and II molecules that present protein Ags, CD1 molecules present lipid Ags for recognition by specific T cells. Each of the five members of the CD1 family (CD1a-e) localizes to a distinct subcompartment of endosomes. Accordingly, it has been widely assumed that the distinct trafficking of CD1 isoforms must also have evolved to enable them to sample lipid Ags that traffic via different routes. Among the CD1 isoforms, CD1a is unusual because it does not have a tyrosine-based cytoplasmic sorting motif and uniquely localizes to the early endocytic recycling compartment. This led us to predict that CD1a might have evolved to focus on lipids that localize to early endocytic/recycling compartments. Strikingly, we found that the glycolipid Ag sulfatide also localized almost exclusively to early endocytic and recycling compartments. Consistent with colocalization of CD1a and sulfatide, wild-type CD1a molecules efficiently presented sulfatide to CD1a-restricted, sulfatide-specific T cells. In contrast, CD1a:CD1b tail chimeras, that retain the same Ag-binding capacity as CD1a but traffic based on the cytoplasmic tail of CD1b to lysosomes, failed to present sulfatide efficiently. Thus, the intracellular trafficking route of CD1a is essential for efficient presentation of lipid Ags that traffic through the early endocytic and recycling pathways.

Maternal Child-Rearing Patterns and Children's Scholastic Achievement in Different Groups.

ERIC Educational Resources Information Center

Logan, Richard D.

The purpose of this study was to examine the general proposition that different maternal child-rearing pattern-types (permissive or restrictive) are associated with high scholastic achievement in elementary school children from four different class-culture groupings (black middle-class, black working-class, white middle-class, and white…

Human umbilical cord mesenchymal stromal cells suppress MHC class II expression on rat vascular endothelium and prolong survival time of cardiac allograft

PubMed Central

Qiu, Ying; Yun, Mark M; Han, Xia; Zhao, Ruidong; Zhou, Erxia; Yun, Sheng

2014-01-01

Background: Human umbilical cord mesenchymal stromal cells (UC-MSCs) have low immunogenicity and immune regulation. To investigate immunomodulatory effects of human UC-MSCs on MHC class II expression and allograft, we transplanted heart of transgenic rats with MHC class II expression on vascular endothelium. Methods: UC-MSCs were obtained from human umbilical cords and confirmed with flow cytometry analysis. Transgenic rat line was established using the construct of human MHC class II transactivator gene (CIITA) under mouse ICAM-2 promoter control. The induced MHC class II expression on transgenic rat vascular endothelial cells (VECs) was assessed with immunohistological staining. And the survival time of cardiac allograft was compared between the recipients with and without UC-MSC transfusion. Results: Flow cytometry confirmed that the human UC-MSCs were positive for CD29, CD44, CD73, CD90, CD105, CD271, and negative for CD34 and HLA-DR. Repeated infusion of human UC-MSCs reduced MHC class II expression on vascular endothelia of transplanted hearts, and increased survival time of allograft. The UC-MSCs increased regulatory cytokines IL10, transforming growth factor (TGF)-β1 and suppressed proinflammatory cytokines IL2 and IFN-γ in vivo. The UC-MSC culture supernatant had similar effects on cytokine expression, and decreased lymphocyte proliferation in vitro. Conclusions: Repeated transfusion of the human UC-MSCs reduced MHC class II expression on vascular endothelia and prolonged the survival time of rat cardiac allograft. PMID:25126177

Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses.

PubMed

Kudelko, Mateusz; Brault, Jean-Baptiste; Kwok, Kevin; Li, Ming Yuan; Pardigon, Nathalie; Peiris, J S Malik; Bruzzone, Roberto; Desprès, Philippe; Nal, Béatrice; Wang, Pei Gang

2012-01-02

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.

Class II ADP-ribosylation Factors Are Required for Efficient Secretion of Dengue Viruses*

PubMed Central

Kudelko, Mateusz; Brault, Jean-Baptiste; Kwok, Kevin; Li, Ming Yuan; Pardigon, Nathalie; Peiris, J. S. Malik; Bruzzone, Roberto; Desprès, Philippe; Nal, Béatrice; Wang, Pei Gang

2012-01-01

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins. PMID:22105072

Morphometric analysis of long-term dentoskeletal effects induced by treatment with Balters bionator.

PubMed

Bigliazzi, Renato; Franchi, Lorenzo; Bertoz, André Pinheiro de Magalhães; McNamara, James A; Faltin, Kurt; Bertoz, Francisco Antonio

2015-09-01

To evaluate the long-term effects of the standard (Class II) Balters bionator in growing patients with Class II malocclusion with mandibular retrusion by using morphometrics (thin-plate spline [TPS] analysis). Twenty-three Class II patients (8 male, 15 female) were treated consecutively with the Balters bionator (bionator group). The sample was evaluated at T0, start of treatment; T1, end of bionator therapy; and T2, long-term observation (including fixed appliances). Mean age at the start of treatment was 10 years 2 months (T0); at posttreatment, 12 years 3 months (T1); and at long-term follow-up, 18 years 2 months (T2). The control group consisted of 22 subjects (11 male, 11 female) with untreated Class II malocclusion. Lateral cephalograms were analyzed at the three time points for all groups. TPS analysis evaluated statistical differences (permutation tests) in the craniofacial shape and size between the bionator and control groups. TPS analysis showed that treatment with the bionator is able to produce favorable mandibular shape changes (forward and downward displacement) that contribute significantly to the correction of the Class II dentoskeletal imbalance. These results are maintained at a long-term observation after completion of growth. The control group showed no statistically significant differences in the correction of Class II malocclusion. This study suggests that bionator treatment of Class II malocclusion produces favorable results over the long term with a combination of skeletal and dentoalveolar shape changes.

The long-term effectiveness of a lifestyle intervention in severely obese individuals.

PubMed

Unick, Jessica L; Beavers, Daniel; Bond, Dale S; Clark, Jeanne M; Jakicic, John M; Kitabchi, Abbas E; Knowler, William C; Wadden, Thomas A; Wagenknecht, Lynne E; Wing, Rena R

2013-03-01

Severe obesity (body mass index [BMI] ≥40 kg/m(2)) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus, nonsurgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared with overweight (25 ≤BMI <30), class I (30 ≤BMI <35), and class II obese (35 ≤BMI <40) participants. There were 5145 individuals with type 2 diabetes (45-76 years, BMI ≥25 kg/m(2)) randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. Four-year changes in body weight and cardiovascular disease risk factors were assessed. Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education (Ps <.05). At year 4, severely obese lifestyle participants lost 4.9%±8.5%, which was similar to class I (4.8%±7.2%) and class II obese participants (4.4%±7.6%), and significantly greater than overweight participants (3.4%±7.0%; P <.05). Four-year changes in low-density-lipoprotein cholesterol, triglycerides, diastolic blood pressure, HbA(1c), and blood glucose were similar across BMI categories in lifestyle participants; however, the severely obese had less favorable improvements in high-density-lipoprotein cholesterol (3.1±0.4 mg/dL) and systolic blood pressure (-1.4±0.7 mm Hg) compared with the less obese (Ps <.05). Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

75 FR 60457 - Underground Injection Control Program Hazardous Waste Injection Restrictions; Petition for...

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2010-09-30

... ENVIRONMENTAL PROTECTION AGENCY [FRL-9208-4] Underground Injection Control Program Hazardous Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection Dow Chemical Company (DOW... Petition. SUMMARY: Notice is hereby given that an exemption to the land disposal restrictions under the...

Modified Angle's Classification for Primary Dentition.

PubMed

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3-6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry.

Functional condition of masseters muscles of patients with class ?? subdivision.

PubMed

Kuroyedova, Vera D; Makarova, Alexandra N; Chicor, Tatyana A

Main functional characteristics of masticator muscles in patients with class ?? malocclusions is activity dominance of m. temporalis in comparison with m. ?asseter. We have not found datum about functional status of the masticators in patients with class II subdivision. The purpose of our study was to investigate the functional characteristics of m. ?asseter, m. temporalis in adult patients with class II subdivision malocclusion. There have been carried out the surface electromyographic study of m. masseter, m. temporalis in 17 adult patients with class II subdivision. It was realized quantitative analysis of 271 electromyogram, it was determined the average bioelectric activity, index activity, symmetry and torsion index. It was observed predominance of the bioelectrical activity of m. temporales on m. masseter for all persons with class II subdivision. Bioelectrical activity for m. masseter was bigger on side of distal ratio and for m. temporales on side of neutral ratio. In class ?? subdivision right, the mandible was deviated to the left side and in class ?? subdivision left is deviated to the right side. Thus, rotational moment generated during compression of the jaws, causes deviation of the lower jaw to the side, with a neutral molar ratio. During voluntary chewing bioelectrical activity of m. masseter and m. temporalis was higher in the right side. In accordance with the functional condition of the masticatory muscles of class II subdivision is characterized with functional features of distal occlusion.

19 CFR 12.17 - Importation restricted.

Code of Federal Regulations, 2011 CFR

2011-04-01

... TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, and Toxins for Treatment of Domestic Animals § 12.17 Importation restricted. The importation into the United States of viruses, serums, toxins, and...

19 CFR 12.17 - Importation restricted.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, and Toxins for Treatment of Domestic Animals § 12.17 Importation restricted. The importation into the United States of viruses, serums, toxins, and...

19 CFR 12.17 - Importation restricted.

Code of Federal Regulations, 2013 CFR

2013-04-01

... TREASURY SPECIAL CLASSES OF MERCHANDISE Viruses, Serums, and Toxins for Treatment of Domestic Animals § 12.17 Importation restricted. The importation into the United States of viruses, serums, toxins, and...

78 FR 37998 - Electronic One Touch Bingo System

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2013-06-25

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77 FR 52109 - Agency Information Collection Activities; Revision of Currently-Approved Information Collection...

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2012-08-28

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HLA Class I and Genetic Susceptibility to Type 1 Diabetes

PubMed Central

Noble, Janelle A.; Valdes, Ana Maria; Varney, Michael D.; Carlson, Joyce A.; Moonsamy, Priscilla; Fear, Anna Lisa; Lane, Julie A.; Lavant, Eva; Rappner, Rebecca; Louey, Anthony; Concannon, Patrick; Mychaleckyj, Josyf C.; Erlich, Henry A.

2010-01-01

OBJECTIVE We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes–associated alleles were B*5701 (odds ratio 0.19; P = 4 × 10−11) and B*3906 (10.31; P = 4 × 10−10). Other significantly type 1 diabetes–associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class II. Other class I type 1 diabetes associations appear to be specific to individual class II haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS These data indicate that HLA class I alleles, in addition to and independently from HLA class II alleles, are associated with type 1 diabetes. PMID:20798335

Class II malocclusion with accentuated occlusal plane inclination corrected with miniplate: a case report

PubMed Central

Farret, Marcel Marchiori; Farret, Milton M. Benitez

2016-01-01

ABSTRACT Introduction: A canted occlusal plane presents an unesthetic element of the smile. The correction of this asymmetry has been typically considered difficult by orthodontists, as it requires complex mechanics and may sometimes even require orthognathic surgery. Objective: This paper outlines the case of a 29-year-old woman with Class II malocclusion, pronounced midline deviation and accentuated occlusal plane inclination caused by mandibular deciduous molar ankylosis. Methods: The patient was treated with a miniplate used to provide anchorage in order to intrude maxillary teeth and extrude mandibular teeth on one side, thus eliminating asymmetry. Class II was corrected on the left side by means of distalization, anchored in the miniplate as well. On the right side, maxillary first premolar was extracted and molar relationship was kept in Class II, while canines were moved to Class I relationship. The patient received implant-prosthetic rehabilitation for maxillary left lateral incisor and mandibular left second premolar. Results: At the end of treatment, Class II was corrected, midlines were matched and the canted occlusal plane was totally corrected, thereby improving smile function and esthetics. PMID:27409658

Uncoupling metallonuclease metal ion binding sites via nudge mutagenesis.

PubMed

Papadakos, Grigorios A; Nastri, Horacio; Riggs, Paul; Dupureur, Cynthia M

2007-05-01

The hydrolysis of phosphodiester bonds by nucleases is critical to nucleic acid processing. Many nucleases utilize metal ion cofactors, and for a number of these enzymes two active-site metal ions have been detected. Testing proposed mechanistic roles for individual bound metal ions has been hampered by the similarity between the sites and cooperative behavior. In the homodimeric PvuII restriction endonuclease, the metal ion dependence of DNA binding is sigmoidal and consistent with two classes of coupled metal ion binding sites. We reasoned that a conservative active-site mutation would perturb the ligand field sufficiently to observe the titration of individual metal ion binding sites without significantly disturbing enzyme function. Indeed, mutation of a Tyr residue 5.5 A from both metal ions in the enzyme-substrate crystal structure (Y94F) renders the metal ion dependence of DNA binding biphasic: two classes of metal ion binding sites become distinct in the presence of DNA. The perturbation in metal ion coordination is supported by 1H-15N heteronuclear single quantum coherence spectra of enzyme-Ca(II) and enzyme-Ca(II)-DNA complexes. Metal ion binding by free Y94F is basically unperturbed: through multiple experiments with different metal ions, the data are consistent with two alkaline earth metal ion binding sites per subunit of low millimolar affinity, behavior which is very similar to that of the wild type. The results presented here indicate a role for the hydroxyl group of Tyr94 in the coupling of metal ion binding sites in the presence of DNA. Its removal causes the affinities for the two metal ion binding sites to be resolved in the presence of substrate. Such tuning of metal ion affinities will be invaluable to efforts to ascertain the contributions of individual bound metal ions to metallonuclease function.

Human tRNA-derived small RNAs in the global regulation of RNA silencing

PubMed Central

Haussecker, Dirk; Huang, Yong; Lau, Ashley; Parameswaran, Poornima; Fire, Andrew Z.; Kay, Mark A.

2010-01-01

Competition between mammalian RNAi-related gene silencing pathways is well documented. It is therefore important to identify all classes of small RNAs to determine their relationship with RNAi and how they affect each other functionally. Here, we identify two types of 5′-phosphate, 3′-hydroxylated human tRNA-derived small RNAs (tsRNAs). tsRNAs differ from microRNAs in being essentially restricted to the cytoplasm and in associating with Argonaute proteins, but not MOV10. The first type belongs to a previously predicted Dicer-dependent class of small RNAs that we find can modestly down-regulate target genes in trans. The 5′ end of type II tsRNA was generated by RNaseZ cleavage downstream from a tRNA gene, while the 3′ end resulted from transcription termination by RNA polymerase III. Consistent with their preferential association with the nonslicing Argonautes 3 and 4, canonical gene silencing activity was not observed for type II tsRNAs. The addition, however, of an oligonucleotide that was sense to the reporter gene, but antisense to an overexpressed version of the type II tsRNA, triggered robust, >80% gene silencing. This correlated with the redirection of the thus reconstituted fully duplexed double-stranded RNA into Argonaute 2, whereas Argonautes 3 and 4 were skewed toward less structured small RNAs, particularly single-strand RNAs. We observed that the modulation of tsRNA levels had minor effects on the abundance of microRNAs, but more pronounced changes in the silencing activities of both microRNAs and siRNAs. These findings support that tsRNAs are involved in the global control of small RNA silencing through differential Argonaute association, suggesting that small RNA-mediated gene regulation may be even more finely regulated than previously realized. PMID:20181738

Unbiased quantitative testing of conventional orthodontic beliefs.

PubMed

Baumrind, S

1998-03-01

This study used a preexisting database to test in hypothesis from the appropriateness of some common orthodontic beliefs concerning upper first molar displacement and changes in facial morphology associated with conventional full bonded/banded treatment in growing subjects. In an initial pass, the author used data from a stratified random sample of 48 subjects drawn retrospectively from the practice of a single, experienced orthodontist. This sample consisted of 4 subgroups of 12 subjects each: Class I nonextraction, Class I extraction, Class II nonextraction, and Class II extraction. The findings indicate that, relative to the facial profile, chin point did not, on average, displace anteriorly during treatment, either overall or in any subgroup. Relative to the facial profile, Point A became significantly less prominent during treatment, both overall and in each subgroup. The best estimate of the mean displacement of the upper molar cusp relative to superimposition on Anterior Cranial Base was in the mesial direction in each of the four subgroups. In only one extraction subject out of 24 did the cusp appear to be displaced distally. Mesial molar cusp displacement was significantly greater in the Class II extraction subgroup than in the Class II nonextraction subgroup. Relative to superimposition on anatomical "best fit" of maxillary structures, the findings for molar cusp displacement were similar, but even more dramatic. Mean mesial migration was highly significant in both the Class II nonextraction and Class II extraction subgroups. In no subject in the entire sample was distal displacement noted relative to this superimposition. Mean increase in anterior Total Face Height was significantly greater in the Class II extraction subgroup than in the Class II nonextraction subgroup. (This finding was contrary to the author's original expectation.) The generalizability of the findings from the initial pass to other treated growing subjects was then assessed by retesting modified hypotheses against a second database stored sample that earlier had been drawn randomly from two other orthodontic practices. The implications of the author's study strategy to the design of future shared digital databases is discussed briefly.

78 FR 76294 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

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2013-12-17

... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; Mosaic... decision on a no migration petition. SUMMARY: Notice is hereby given that an exemption to the land disposal Restrictions, under the 1984 Hazardous and Solid Waste Amendments to the Resource Conservation and Recovery Act...

76 FR 55908 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

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2011-09-09

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76 FR 36129 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

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2011-06-21

... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; ExxonMobil... final decision on a no migration petition. SUMMARY: Notice is hereby given that an exemption to the land disposal Restrictions, under the 1984 Hazardous and Solid Waste Amendments to the Resource Conservation and...

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77 FR 26755 - Underground Injection Control Program; Hazardous Waste Injection Restrictions; Petition for...

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Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-18

... Waste Injection Restrictions; Petition for Exemption--Class I Hazardous Waste Injection; ConocoPhillips... no migration petition. SUMMARY: Notice is hereby given that an exemption to the land disposal Restrictions, under the 1984 Hazardous and Solid Waste Amendments to the Resource Conservation and Recovery Act...

Cone-beam computed tomographic evaluation of the temporomandibular joint and dental characteristics of patients with Class II subdivision malocclusion and asymmetry

PubMed Central

Huang, Mingna; Hu, Yun; Yu, Jinfeng; Sun, Jicheng; Ming, Ye

2017-01-01

Objective Treating Class II subdivision malocclusion with asymmetry has been a challenge for orthodontists because of the complicated characteristics of asymmetry. This study aimed to explore the characteristics of dental and skeletal asymmetry in Class II subdivision malocclusion, and to assess the relationship between the condyle-glenoid fossa and first molar. Methods Cone-beam computed tomographic images of 32 patients with Class II subdivision malocclusion were three-dimensionally reconstructed using the Mimics software. Forty-five anatomic landmarks on the reconstructed structures were selected and 27 linear and angular measurements were performed. Paired-samples t-tests were used to compare the average differences between the Class I and Class II sides; Pearson correlation coefficient (r) was used for analyzing the linear association. Results The faciolingual crown angulation of the mandibular first molar (p < 0.05), sagittal position of the maxillary and mandibular first molars (p < 0.01), condylar head height (p < 0.01), condylar process height (p < 0.05), and angle of the posterior wall of the articular tubercle and coronal position of the glenoid fossa (p < 0.01) were significantly different between the two sides. The morphology and position of the condyle-glenoid fossa significantly correlated with the three-dimensional changes in the first molar. Conclusions Asymmetry in the sagittal position of the maxillary and mandibular first molars between the two sides and significant lingual inclination of the mandibular first molar on the Class II side were the dental characteristics of Class II subdivision malocclusion. Condylar morphology and glenoid fossa position asymmetries were the major components of skeletal asymmetry and were well correlated with the three-dimensional position of the first molar. PMID:28861389

Characterization of the molecular chaperone calnexin in the channel catfish, Ictalurus punctatus, and its association with MHC class II molecules.

PubMed

Fuller, James R; Pitzer, Joshua E; Godwin, Ulla; Albertino, Mark; Machon, Benjamin D; Kearse, Kelly P; McConnell, Thomas J

2004-05-17

Folding and assembly of MHC molecules in mammals occurs in the endoplasmic reticulum (ER), but has not been studied in teleosts. Calnexin (CNX) is an ER chaperone that associates with glycoproteins bearing a monoglucosylated N-linked oligosaccharide side chain. Here we report the first identification and characterization of a full-length CNX cDNA clone in a teleost, and the association of the CNX chaperone with MHC class II in a channel catfish T cell line. The 1.8 kb CNX clone encodes a protein of 607 amino acids that is 72% identical to the consensus sequence of mammalian CNXs. The association of CNX with class II is of particular interest because the native MHC class II alpha chain of Ictalurus punctatus does not bear any N-linked oligosaccharide consensus glycosylation sequences. Thus the assembly of class II molecules in the catfish probably proceeds via different steps than occurs in mammals. Copyright 2003 Elsevier Ltd.

Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins

NASA Technical Reports Server (NTRS)

Beharka, A. A.; Armstrong, J. W.; Iandolo, J. J.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Macrophages from C2D transgenic mice deficient in the expression of major histocompatibility complex (MHC) class II proteins were used to identify binding sites for superantigens distinct from the MHC class II molecule. Iodinated staphylococcal enterotoxins A and B (SEA and SEB) and exfoliative toxins A and B (ETA and ETB) bound to C2D macrophages in a concentration-dependent and competitive manner. All four toxins increased F-actin concentration within 30 s of their addition to C2D macrophages, indicating that signal transduction occurred in response to toxin in the absence of class II MHC. Furthermore, ETA, ETB, SEA, and, to a lesser extent, SEB induced C2D macrophages to produce interleukin 6. Several molecular species on C2D macrophages with molecular masses of 140, 97, 61, 52, 43, and 37 kDa bound SEA in immunoprecipitation experiments. These data indicate the presence of novel, functionally active toxin binding sites on murine macrophages distinct from MHC class II molecules.

Tolerance to MHC class II disparate allografts through genetic modification of bone marrow

PubMed Central

Jindra, Peter T.; Tripathi, Sudipta; Tian, Chaorui; Iacomini, John; Bagley, Jessamyn

2012-01-01

Induction of molecular chimerism through genetic modification of bone marrow is a powerful tool for the induction of tolerance. Here we demonstrate for the first time that expression of an allogeneic MHC class II gene in autologous bone marrow cells, resulting in a state of molecular chimerism, induces tolerance to MHC class II mismatched skin grafts, a stringent test of transplant tolerance. Reconstitution of recipients with syngeneic bone marrow transduced with retrovirus encoding H-2I-Ab (I-Ab) resulted the long-term expression of the retroviral gene product on the surface of MHC class II-expressing bone marrow derived cell types. Mechanistically, tolerance was maintained by the presence of regulatory T cells, which prevented proliferation and cytokine production by alloreactive host T cells. Thus, the introduction of MHC class II genes into bone marrow derived cells through genetic engineering results in tolerance. These results have the potential to extend the clinical applicability of molecular chimerism for tolerance induction. PMID:22833118

Cross-presentation of IgG-containing immune complexes

PubMed Central

Baker, Kristi; Rath, Timo; Lencer, Wayne I.; Fiebiger, Edda

2012-01-01

IgG is a molecule that functionally combines facets of both innate and adaptive immunity and therefore bridges both arms of the immune system. On the one hand, IgG is created by adaptive immune cells, but can be generated by B cells independently of T cell help. On the other hand, once secreted, IgG can rapidly deliver antigens into intracellular processing pathways, which enable efficient priming of T cell responses towards epitopes from the cognate antigen initially bound by the IgG. While this process has long been known to participate in CD4+ T cell activation, IgG-mediated delivery of exogenous antigens into a major histocompatibility complex (MHC) class I processing pathway has received less attention. The coordinated engagement of IgG with IgG receptors expressed on the cell-surface (FcγR) and within the endolysosomal system (FcRn) is a highly potent means to deliver antigen into processing pathways that promote cross-presentation of MHC class I and presentation of MHC class II-restricted epitopes within the same dendritic cell. This review focuses on the mechanisms by which IgG-containing immune complexes mediate such cross-presentation and the implications that this understanding has for manipulation of immune-mediated diseases that depend upon or are due to the activities of CD8+ T cells. PMID:22847331

HLA Engineering of Human Pluripotent Stem Cells

PubMed Central

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-01-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I–negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8+ T cell responses were reduced in class I–negative cells that had undergone differentiation in embryoid bodies. These B2M−/− ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines. PMID:23629003

HLA engineering of human pluripotent stem cells.

PubMed

Riolobos, Laura; Hirata, Roli K; Turtle, Cameron J; Wang, Pei-Rong; Gornalusse, German G; Zavajlevski, Maja; Riddell, Stanley R; Russell, David W

2013-06-01

The clinical use of human pluripotent stem cells and their derivatives is limited by the rejection of transplanted cells due to differences in their human leukocyte antigen (HLA) genes. This has led to the proposed use of histocompatible, patient-specific stem cells; however, the preparation of many different stem cell lines for clinical use is a daunting task. Here, we develop two distinct genetic engineering approaches that address this problem. First, we use a combination of gene targeting and mitotic recombination to derive HLA-homozygous embryonic stem cell (ESC) subclones from an HLA-heterozygous parental line. A small bank of HLA-homozygous stem cells with common haplotypes would match a significant proportion of the population. Second, we derive HLA class I-negative cells by targeted disruption of both alleles of the Beta-2 Microglobulin (B2M) gene in ESCs. Mixed leukocyte reactions and peptide-specific HLA-restricted CD8(+) T cell responses were reduced in class I-negative cells that had undergone differentiation in embryoid bodies. These B2M(-/-) ESCs could act as universal donor cells in applications where the transplanted cells do not express HLA class II genes. Both approaches used adeno-associated virus (AAV) vectors for efficient gene targeting in the absence of potentially genotoxic nucleases, and produced pluripotent, transgene-free cell lines.

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

PubMed Central

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

Clinical assessment of class II resin-based composites versus preformed metal crowns performed on primary molars in patients at high risk of caries.

PubMed

Alyahya, A; Khanum, A; Qudeimat, M

2018-02-01

To compare class II resin composite with preformed metal crowns (PMC) in the treatment of proximal dentinal caries in high caries-risk patients. The charts (270) of paediatric patients with proximal caries of their primary molars were reviewed. Success or failure of a procedure was assessed using the dental notes. Survival analysis was used to calculate the mean survival time (MST) for both procedures. The influence of variables on the mean survival time was investigated. A total of 593 class II resin composites and 243 PMCs were placed in patients ranging between 4-13 years of age. The failure percentage of class II resin composites was 22.6% with the majority having been due to recurrent caries, while the failure percentage of PMCs was 15.2% with the majority due to loss of the crown. There was no significant difference between the MST of class II resin composites and PMCs, 41.3 and 45.6 months respectively (p value = 0.06). In class II resin composites, mesial restorations were associated with lower MST compared to distal restorations (p-value < 0.001). The MST of resin composites and PMCs were comparable when performed on high caries-risk patients.

Active site nanospace of aminoacyl tRNA synthetase: difference between the class I and class II synthetases.

PubMed

Dutta, Saheb; Choudhury, Kaberi; Banik, Sindrila Dutta; Nandi, Nilashis

2014-03-01

The present work is aimed at understanding the origin of the difference in the molecular organization of the active site nanospaces of the class I and class II aminoacyl tRNA synthetases (aaRSs) which are tunnel-like structures. The active site encloses the cognate amino acid (AA) and the adenosine triphosphate (ATP) to carry out aminoacylation reaction. Comparison of the structures of the active site of the class I and class II (aaRSs) shows that the nanodimensional tunnels are curved in opposite directions in the two classes. We investigated the origin of this difference using quantum mechanical computation of electrostatic potential (ESP) of substrates, surrounding residues and ions, using Atoms in Molecule (AIM) Theory and charge population analysis. We show that the difference is principally due to the variation in the spatial charge distribution of ATP in the two classes which correspond to extended and bent conformations of ATP. The present computation shows that the most feasible pathway for nucleophilic attack to alphaP is oppositely directed for class I and class II aaRSs. The available crystal structures show that the cognate AA is indeed located along the channel favorable for nucleophilic attack as predicted by the ESP analysis. It is also shown that the direction of the channel changes its orientation when the orientation of ATP is changed from extended to a bent like structure. We further used the AIM theory to confirm the direction of the approach of AA in each case and the results corroborate the results from the ESP analysis. The opposite curvatures of the active site nanospaces in class I and class II aaRSs are related with the influence of the charge distributions of the extended and bent conformations of ATP, respectively. The results of the computation of electrostatic potential by successive addition of active site residues show that their roles on the reaction are similar in both classes despite the difference in the organization of the active sites of class I and class II aaRSs. The difference in mechanism in two classes as pointed out in recent study (S. Dutta Banik and N. Nandi, J. Biomol. Struct. Dyn. 30, 701 (2012)) is related with the fact that the relative arrangement of the ATP with respect to the AA is opposite in class I and class II aaRSs as explained in the present work. The charge population difference between the reacting centers (which are the alphaP atom of ATP (q(p)) and the attacking oxygen atom of carboxylic acid group (q(o)), respectively) denoted by delta(q), is a measure of the propensity of nucleophilic attack. The population analysis of the substrate AA shows that a non-negligible difference exists between the attacking oxygens of AA in class I (syn) and in class II (anti) which is one reason for the lower value of delta(q) in class II relative to class I. The population analysis of the AA, ATP, Mg+2 ions and active site residues shows that the difference in delta(q) values of the two classes is substantially reduced. When ions and residues are considered. Thus, the bent state of ATP, Mg+2 ions and active site residues complements it cognate AA to carry out the nucleophilic reaction in class I as efficiently as occurs in class I (with the extended state of ATP, single Mg+2 ion and active site residues). This could be one reason for the two different conformations of ATP in the two classes. The mutual arrangements of AA and ATP in each aaRS are guided by the spatial charge distribution of ATP (extended and bent). The present work shows that the construction of nanospace complements the arrangement of the substrate (AA and ATP).

Coexistence of group I and group II chaperonins in the archaeon Methanosarcina mazei.

PubMed

Klunker, Daniel; Haas, Bernd; Hirtreiter, Angela; Figueiredo, Luis; Naylor, Dean J; Pfeifer, Günter; Müller, Volker; Deppenmeier, Uwe; Gottschalk, Gerhard; Hartl, F Ulrich; Hayer-Hartl, Manajit

2003-08-29

Two distantly related classes of cylindrical chaperonin complexes assist in the folding of newly synthesized and stress-denatured proteins in an ATP-dependent manner. Group I chaperonins are thought to be restricted to the cytosol of bacteria and to mitochondria and chloroplasts, whereas the group II chaperonins are found in the archaeal and eukaryotic cytosol. Here we show that members of the archaeal genus Methanosarcina co-express both the complete group I (GroEL/GroES) and group II (thermosome/prefoldin) chaperonin systems in their cytosol. These mesophilic archaea have acquired between 20 and 35% of their genes by lateral gene transfer from bacteria. In Methanosarcina mazei Gö1, both chaperonins are similarly abundant and are moderately induced under heat stress. The M. mazei GroEL/GroES proteins have the structural features of their bacterial counterparts. The thermosome contains three paralogous subunits, alpha, beta, and gamma, which assemble preferentially at a molar ratio of 2:1:1. As shown in vitro, the assembly reaction is dependent on ATP/Mg2+ or ADP/Mg2+ and the regulatory role of the beta subunit. The co-existence of both chaperonin systems in the same cellular compartment suggests the Methanosarcina species as useful model systems in studying the differential substrate specificity of the group I and II chaperonins and in elucidating how newly synthesized proteins are sorted from the ribosome to the proper chaperonin for folding.

A WISE CENSUS OF YOUNG STELLAR OBJECTS IN CANIS MAJOR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischer, William J.; Padgett, Deborah L.; Sewiło, Marta

With the Wide-field Infrared Survey Explorer (WISE), we searched for young stellar objects (YSOs) in a 100 deg{sup 2} region centered on the lightly studied Canis Major star-forming region. Applying stringent magnitude cuts to exclude the majority of extragalactic contaminants, we find 144 Class I candidates and 335 Class II candidates. The sensitivity to Class II candidates is limited by their faintness at the distance to Canis Major (assumed as 1000 pc). More than half the candidates (53%) are found in 16 groups of more than four members, including four groups with more than 25 members each. The ratio ofmore » Class II to Class I objects, N {sub II}/ N {sub I}, varies from 0.4 to 8.3 in just the largest four groups. We compare our results to those obtainable with combined Two Micron All Sky Survey and post-cryogenic Spitzer Space Telescope data; the latter approach recovers missing Class II sources. Via a comparison to protostars characterized with the Herschel Space Observatory , we propose new WISE color criteria for flat-spectrum and Class 0 protostars, finding 80 and 7 of these, respectively. The distribution of YSOs in CMa OB1 is consistent with supernova-induced star formation, although the diverse N {sub II}/ N {sub I} ratios are unexpected if this parameter traces age and the YSOs are due to the same supernova. Less massive clouds feature larger N {sub II}/ N {sub I} ratios, suggesting that initial conditions play a role in determining this quantity.« less

Star Formation and Young Population of the H II Complex Sh2-294

NASA Astrophysics Data System (ADS)

Samal, M. R.; Pandey, A. K.; Ojha, D. K.; Chauhan, N.; Jose, J.; Pandey, B.

2012-08-01

The Sh2-294 H II region ionized by a single B0V star features several infrared excess sources, a photodissociation region, and also a group of reddened stars at its border. The star formation scenario in this region seems to be quite complex. In this paper, we present follow-up results of Sh2-294 H II region at 3.6, 4.5, 5.8, and 8.0 μm observed with the Spitzer Space Telescope Infrared Array Camera (IRAC), coupled with H2 (2.12 μm) observation, to characterize the young population of the region and to understand its star formation history. We identified 36 young stellar object (YSO, Class I, Class II, and Class I/II) candidates using IRAC color-color diagrams. It is found that Class I sources are preferentially located at the outskirts of the H II region and associated with enhanced H2 emission; none of them are located near the central cluster. Combining the optical to mid-infrared (MIR) photometry of the YSO candidates and using the spectral energy distribution fitting models, we constrained stellar parameters and the evolutionary status of 33 YSO candidates. Most of them are interpreted by the model as low-mass (<4 M ⊙) YSOs; however, we also detected a massive YSO (~9 M ⊙) of Class I nature, embedded in a cloud of visual extinction of ~24 mag. Present analysis suggests that the Class I sources are indeed a younger population of the region relative to Class II sources (age ~ 4.5 × 106 yr). We suggest that the majority of the Class I sources, including the massive YSOs, are second-generation stars of the region whose formation is possibly induced by the expansion of the H II region powered by a ~4 × 106 yr B0 main-sequence star.

Hyperhidrosis: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins

PubMed Central

Lakraj, Amanda-Amrita D.; Moghimi, Narges; Jabbari, Bahman

2013-01-01

Clinical features, anatomy and physiology of hyperhidrosis are presented with a review of the world literature on treatment. Level of drug efficacy is defined according to the guidelines of the American Academy of Neurology. Topical agents (glycopyrrolate and methylsulfate) are evidence level B (probably effective). Oral agents (oxybutynin and methantheline bromide) are also level B. In a total of 831 patients, 1 class I and 2 class II blinded studies showed level B efficacy of OnabotulinumtoxinA (A/Ona), while 1 class I and 1 class II study also demonstrated level B efficacy of AbobotulinumtoxinA (A/Abo) in axillary hyperhidrosis (AH), collectively depicting Level A evidence (established) for botulinumtoxinA (BoNT-A). In a comparator study, A/Ona and A/Inco toxins demonstrated comparable efficacy in AH. For IncobotulinumtoxinA (A/Inco) no placebo controlled studies exist; thus, efficacy is Level C (possibly effective) based solely on the aforementioned class II comparator study. For RimabotulinumtoxinB (B/Rima), one class III study has suggested Level U efficacy (insufficient data). In palmar hyperhidrosis (PH), there are 3 class II studies for A/Ona and 2 for A/Abo (individually and collectively level B for BoNT-A) and no blinded study for A/Inco (level U). For B/Rima the level of evidence is C (possibly effective) based on 1 class II study. Botulinum toxins (BoNT) provide a long lasting effect of 3–9 months after one injection session. Studies on BoNT-A iontophoresis are emerging (2 class II studies; level B); however, data on duration and frequency of application is inconsistent. PMID:23612753

HLA-typing analysis following allogeneic bone grafting for sinus lifting.

PubMed

Piaia, Marcelo; Bub, Carolina Bonet; Succi, Guilherme de Menezes; Torres, Margareth; Costa, Thiago Henrique; Pinheiro, Fabricio Costa; Napimoga, Marcelo Henrique

2017-03-01

According to the Brazilian Association of Organ Transplants, in 2015, 19,408 bone transplants were performed in Brazil, over 90% by Dental Surgeons. The surgical technique itself has a respectable number of reports regarding its clinical efficacy, as measured by long-term survival of dental implants in grafted areas. Uncertainty remains, however, as to whether fresh frozen grafts from human bone donors remain immunologically innocuous in the body of the host. Six male with no previous medical history of note, including systemic diseases, surgery or blood transfusion were selected. These patients underwent reconstructive procedures (sinus lifting) using fresh frozen human bone from a tissue bank. All patients had venous blood samples collected prior to surgery and 6 months after the procedure. Anti-HLA analysis for the detection of HLA (human leukocyte antigen) antibodies was performed using methods such as the LABScreen PRA Class I and Class II, LABScreen Single Antigen Class I and Class II, Luminex Platform. Reactive individuals to the screening tests (LABScreen PRA) were further investigated to determine the specificity of the antibodies detected (LABScreen Single Antigen) with a cutoff value of median fluorescence intensity ≥500. As a result, it was observed that two patients (33%) were positive in screening tests, one presenting with anti-HLA Class I and II sensitization and the other with anti-HLA class II. The specificity analysis showed that the patients sensitized to HLA class II presented 4 specificities, 3 of which immunologically relevant. In the second individual, 23 specificities were identified, 6 of which immunologically important for HLA class I and 4 specificities for HLA class II, 3 of these were immunologically important. All specificities detected had average fluorescence. These findings are suggestive that sinus-lifting procedures with allogeneic bone can induce immunological sensitization.

Expression of inducible nitric oxide synthase in spontaneous bovine bronchopneumonia.

PubMed

Fligger, J M; Waldvogel, A S; Pfister, H; Jungi, T W

1999-09-01

The expression of inducible nitric oxide synthase (iNOS), major histocompatibility class II molecules (MHC-II), CD68, and the calcium-binding proteins S100A8 and S100A9 (also called MRP8 and MRP14, respectively) was assessed in lung tissues from cattle that succumbed to pneumonia. Expression patterns of these markers were related to the types of lung lesion. iNOS expression was only observed in lungs infected with Arcanobacterium pyogenes or Pasteurella haemolytica but not in lungs from cattle with subacute chronic interstitial pneumonia and acute interstitial pneumonia due to Escherichia coli infection. High levels of iNOS were expressed by cells (probably leukocytes) surrounding necrotic foci. Occasionally, iNOS was expressed by intraalveolar macrophages in viable parenchyma, by leukocytes within the airways, and by some chondrocytes in the supporting cartilage of bronchi. Cells expressing MHC-II were distributed relatively evenly throughout areas of inflammation and did not display any clear association with necrotic foci. Cell types expressing MHC-II included type II alveolar epithelial cells, spindle-shaped cells of the interstitium, cells in bronchus-associated lymphoid tissue, and leukocytes in lymph and blood vessels but largely excluded iNOS-positive cells. Likewise, CD68-positive cells were rarely positive for iNOS and were not confined to the areas surrounding necrotic tissue. As with MHC-II and CD68, there was little if any coexpression of iNOS and either of the S100 proteins tested. Thus, in cattle with necrotizing bronchopneumonia, iNOS-expressing cells were largely restricted to the cellular zone surrounding necrotic areas.

Sequential cloning of chromosomes

DOEpatents

Lacks, Sanford A.

1995-07-18

A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism's chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes.

Modified Angle's Classification for Primary Dentition

PubMed Central

Chandranee, Kaushik Narendra; Chandranee, Narendra Jayantilal; Nagpal, Devendra; Lamba, Gagandeep; Choudhari, Purva; Hotwani, Kavita

2017-01-01

Aim: This study aims to propose a modification of Angle's classification for primary dentition and to assess its applicability in children from Central India, Nagpur. Methods: Modification in Angle's classification has been proposed for application in primary dentition. Small roman numbers i/ii/iii are used for primary dentition notation to represent Angle's Class I/II/III molar relationships as in permanent dentition, respectively. To assess applicability of modified Angle's classification a cross-sectional preschool 2000 children population from central India; 3–6 years of age residing in Nagpur metropolitan city of Maharashtra state were selected randomly as per the inclusion and exclusion criteria. Results: Majority 93.35% children were found to have bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half cusp Class iii molar relationships as per the modified Angle's classification for primary dentition. About 3.75% children had various combinations of Class ii relationships and 0.2% children were having Class iii subdivision relationship. Conclusions: Modification of Angle's classification for application in primary dentition has been proposed. A cross-sectional investigation using new classification revealed various 6.25% Class ii and 0.4% Class iii molar relationships cases in preschool children population in a metropolitan city of Nagpur. Application of the modified Angle's classification to other population groups is warranted to validate its routine application in clinical pediatric dentistry. PMID:29326514

MHC class II-assortative mate choice in European badgers (Meles meles).

PubMed

Sin, Yung Wa; Annavi, Geetha; Newman, Chris; Buesching, Christina; Burke, Terry; Macdonald, David W; Dugdale, Hannah L

2015-06-01

The major histocompatibility complex (MHC) plays a crucial role in the immune system, and in some species, it is a target by which individuals choose mates to optimize the fitness of their offspring, potentially mediated by olfactory cues. Under the genetic compatibility hypothesis, individuals are predicted to choose mates with compatible MHC alleles, to increase the fitness of their offspring. Studies of MHC-based mate choice in wild mammals are under-represented currently, and few investigate more than one class of MHC genes. We investigated mate choice based on the compatibility of MHC class I and II genes in a wild population of European badgers (Meles meles). We also investigated mate choice based on microsatellite-derived pairwise relatedness, to attempt to distinguish MHC-specific effects from genomewide effects. We found MHC-assortative mating, based on MHC class II, but not class I genes. Parent pairs had smaller MHC class II DRB amino acid distances and smaller functional distances than expected from random pairings. When we separated the analyses into within-group and neighbouring-group parent pairs, only neighbouring-group pairs showed MHC-assortative mating, due to similarity at MHC class II loci. Our randomizations showed no evidence of genomewide-based inbreeding, based on 35 microsatellite loci; MHC class II similarity was therefore the apparent target of mate choice. We propose that MHC-assortative mate choice may be a local adaptation to endemic pathogens, and this assortative mate choice may have contributed to the low MHC genetic diversity in this population. © 2015 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.

Characterization of MHC class I and II genes in a subantarctic seabird, the blue petrel, Halobaena caerulea (Procellariiformes).

PubMed

Strandh, Maria; Lannefors, Mimi; Bonadonna, Francesco; Westerdahl, Helena

2011-10-01

The great polymorphism observed in the major histocompatibility complex (MHC) genes is thought to be maintained by pathogen-mediated selection possibly combined with MHC-disassortative mating, guided by MHC-determined olfactory cues. Here, we partly characterize the MHC class I and II B of the blue petrel, Halobaena caerulea (Procellariiformes), a bird with significant olfactory abilities that lives under presumably low pathogen burdens in Subantarctica. Blue petrels are long-lived, monogamous birds which suggest the necessity of an accurate mate choice process. The species is ancestral to songbirds (Passeriformes; many MHC loci), although not to gamefowls (Galliformes; few MHC loci). Considering the phylogenetic relationships and the low subantarctic pathogen burden, we expected few rather than many MHC loci in the blue petrel. However, when we analysed partial MHC class I and class II B cDNA and gDNA sequences we found evidence for as many as at least eight MHC class I loci and at least two class II B loci. These class I and II B sequences showed classical MHC characteristics, e.g. high nucleotide diversity, especially in putative peptide-binding regions where signatures of positive selection was detected. Trans-species polymorphism was found between MHC class II B sequences of the blue petrel and those of thin-billed prion, Pachyptila belcheri, two species that diverged ∼25 MYA. The observed MHC allele richness in the blue petrel may well serve as a basis for mate choice, especially since olfactory discrimination of MHC types may be possible in this species.

77 FR 43861 - Importer of Controlled Substances; Notice Of Application; Cody Laboratories, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-26

... basic class of any controlled substance in schedule I or II are, and will continue to be, required to... importer of the following basic classes of controlled substances: Drug Schedule Opium, Raw (9600) II Concentrate Poppy Straw (9670) II Tapentadol (9780) II The company plans to import narcotic raw materials for...

Measurement of ex vivo ELISpot interferon-gamma recall responses to Plasmodium falciparum AMA1 and CSP in Ghanaian adults with natural exposure to malaria.

PubMed

Ganeshan, Harini; Kusi, Kwadwo A; Anum, Dorothy; Hollingdale, Michael R; Peters, Bjoern; Kim, Yohan; Tetteh, John K A; Ofori, Michael F; Gyan, Ben A; Koram, Kwadwo A; Huang, Jun; Belmonte, Maria; Banania, Jo Glenna; Dodoo, Daniel; Villasante, Eileen; Sedegah, Martha

2016-02-01

Malaria eradication requires a concerted approach involving all available control tools, and an effective vaccine would complement these efforts. An effective malaria vaccine should be able to induce protective immune responses in a genetically diverse population. Identification of immunodominant T cell epitopes will assist in determining if candidate vaccines will be immunogenic in malaria-endemic areas. This study therefore investigated whether class I-restricted T cell epitopes of two leading malaria vaccine antigens, Plasmodium falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1), could recall T cell interferon-γ responses from naturally exposed subjects using ex vivo ELISpot assays. Thirty-five subjects aged between 24 and 43 years were recruited from a malaria-endemic urban community of Ghana in 2011, and their peripheral blood mononuclear cells (PBMCs) were tested in ELISpot IFN-γ assays against overlapping 15mer peptide pools spanning the entire CSP and AMA1 antigens, and 9-10mer peptide epitope mixtures that included previously identified and/or predicted human leukocyte antigen (HLA) class 1-restricted epitopes from same two antigens. For CSP, 26 % of subjects responded to at least one of the nine 15mer peptide pools whilst 17 % responded to at least one of the five 9-10mer HLA-restricted epitope mixtures. For AMA1, 63 % of subjects responded to at least one of the 12 AMA1 15mer peptide pools and 51 % responded to at least one of the six 9-10mer HLA-restricted epitope mixtures. Following analysis of data from the two sets of peptide pools, along with bioinformatics predictions of class I-restricted epitopes and the HLA supertypes expressed by a subset of study subjects, peptide pools that may contain epitopes recognized by multiple HLA supertypes were identified. Collectively, these results suggest that natural transmission elicits ELISpot IFN-γ activities to class 1-restricted epitopes that are largely HLA-promiscuous. These results generally demonstrate that CSP and AMA1 peptides recalled ELISpot IFN-γ responses from naturally exposed individuals and that both CSP and AMA1 contain diverse class 1-restricted epitopes that are HLA-promiscuous and are widely recognized in this population.

The effects of forehead and neck position on esthetics of class I, II and III profiles.

PubMed

Salehi, Parisa; Oshagh, Morteza; Aleyasin, Zeinab S; Pakshir, Hamid Reza

2014-01-01

All parts of the face, other than jaw relationships, should be considered in orthodontic treatment planning. The role of forehead and neck in facial esthetics is well known; however, the majority of conventional facial analysis methods have not considered them. Neck and forehead may confer mutual effects on equilibrium and on esthetics of other facial components, and may change the overall convexity/concavity view of the profile. Therefore, the aim of this study was to assess the effect of anteroposterior position of the forehead and neck on the esthetics of skeletal class I, II and III jaw relationships using profile silhouettes. Class II and III jaw relationships were constructed on the silhouette of a class I normal profile by altering the mandibular position. Retruded, normal and protruded positions were also applied for the forehead and neck. Three hundred Iranian laypeople (150 men, 150 women) scored the esthetics of profile silhouettes from 1 to 7. Half of the participants were told to consider the profiles as a man, and the other half were told to consider them as a woman. Data were analyzed using non-parametric methods. Class I jaw relation was found to be the most beautiful profile followed by class II and III respectively. Esthetics of different positions of the neck and forehead were significantly different (P < 0.05). In subjects with a normal neck and forehead position, and those with a retruded neck, the best esthetic relationship was class I, and the worst was class III. For protruded foreheads, the best jaw relationship was class II for females and class I for males, and the worst was class III for both. In a retruded forehead position, the most preferred jaw relationship was class I, and the worst was class II. For profiles with a protruded neck, the best esthetics was found to be in class III jaw relationship, and the worst was in class II. There was a small difference in scoring for male and female profiles (P < 0.05); there were also small differences in scoring trends of men and women (P < 0.05). This study showed that the anteroposterior position of the forehead and neck affects the esthetics of jaw relationships in profile view. In laypeople's opinions, in a normal profile, the overall appearance is more important compared to the independent position of the neck and forehead; however, having jaw abnormalities, the neck plays an important independent role. The preferred jaw relation for profiles with each forehead or neck position was introduced.

NLRC5: a key regulator of MHC class I-dependent immune responses.

PubMed

Kobayashi, Koichi S; van den Elsen, Peter J

2012-12-01

The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

[Study on the difference of corresponding age at cervical vertebral maturation stages among different skeletal malocclusions].

PubMed

Zuo, Changyan; Cong, Chao; Wang, Shihui; Gu, Yan

2015-10-01

To compare the difference of corresponding age at cervical vertebral maturation (CVM) stages among different skeletal malocclusions and provide clinic guideline on optimal treatment timing for skeletal malocclusion. Based on ANB angle, 2 575 cephalograms collected from Department of Orthodontics, Peking University School and Hospital of Stomatology from May, 2006 to November, 2014 were classified into skeletal Class I (ANB 0°~5°, 1 317 subjects), Class II (ANB > 5°, 685 subjects) and Class III (ANB < 0°, 573 subjects) groups. CVM stages were evaluated with the modified version of CVM method. Independent sample t test was performed to analyze the difference of age at different CVM stages among various skeletal groups. Significant gender difference of age was found at CS3 to CS6 for skeletal Class I group (P < 0.05), at CS5 and CS6 for skeletal Class II group (P < 0.05), and at CS3 and CS5 for skeletal Class III group (P < 0.05). At CS3 stage, the average age of male in skeletal Class II and skeletal Class III groups was (11.6 ± 1.5) years old and (10.3 ± 1.9) years old, respectively; the average age of females in those two groups was (11.7 ± 1.3) years old and (9.3 ± 1.5) years old, respectively, and significant difference was found in both comparisons (P < 0.05). Compared average age at CS5 and CS6 between skeletal Class II and skeletal Class III groups [the ages of male was (15.1 ± 1.7) and (16.8 ± 1.6) years old, the ages of male was (14.6 ± 1.2) and (15.7 ± 2.5) years old], significant difference was also found (P < 0.05). Significant gender differences were found when evaluated CVM stage and age in skeletal Class I, II and III groups. Significant differences of age at different CVM stage was noted when skeletal Class II was compared with skeletal Class III groups.

[Morphological analysis of alveolar bone of anterior mandible in high-angle skeletal class II and class III malocclusions assessed with cone-beam computed tomography].

PubMed

Ma, J; Jiang, J H

2018-02-18

To evaluate the difference of features of alveolar bone support under lower anterior teeth between high-angle adults with skeletal class II malocclusions and high-angle adults presenting skeletal class III malocclusions by using cone-beam computed tomography (CBCT). Patients who had taken the images of CBCT were selected from the Peking University School and Hospital of Stomatology between October 2015 and August 2017. The CBCT archives from 62 high-angle adult cases without orthodontic treatment were divided into two groups based on their sagittal jaw relationships: skeletal class II and skeletal class III. vertical bone level (VBL), alveolar bone area (ABA), and the width of alveolar bone were measured respectively at the 2 mm, 4 mm, 6 mm below the cemento-enamel junction (CEJ) level and at the apical level. After that, independent samples t-tests were conducted for statistical comparisons. The ABA of the mandibular alveolar bone in the area of lower anterior teeth was significantly thinner in the patients of skeletal class III than those of skeletal class II, especially in terms of the apical ABA, total ABA on the labial and lingual sides and the ABA at 6 mm below CEJ level on the lingual side (P<0.05). The thickness of the alveolar bone of mandibular anterior teeth was significantly thinner in the subjects of skeletal class III than those of skeletal class II, especially regarding the apical level on the labial and lingual side and at the level of 4 mm, 6 mm below CEJ level on the lingual side (P<0.05). The ABA and the thickness of the alveolar bone of mandibular anterior teeth were significantly thinner in the group of skeletal class III adult patients with high-angle when compared with the sample of high-angle skeletal class II adult cases. We recommend orthodontists to be more cautious in treatment of high-angle skeletal class III patients, especially pay attention to control the torque of lower anterior teeth during forward and backward movement, in case that the apical root might be absorbed or fenestration happen in the area of lower anterior teeth.

50 CFR 679.90 - Allocation, use, and transfer of Amendment 80 QS permits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Restricted Access Management Program, NMFS, P.O. Box 21668, Juneau, AK 99802-1668; (ii) Fax: 907-586-7354; or (iii) Hand delivery or carrier: NMFS, Room 713, 709 West 9th Street, Juneau, AK 99801. (2) Application... Administrator, c/o Restricted Access Management Program, NMFS, P.O. Box 21668, Juneau, AK 99802-1668; (ii) Fax...

40 CFR 147.3106 - Area of review.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chapter, the fixed radius shall be no less than one mile for Class I wells and one-half mile for Class II... under § 146.6(b) shall be a fixed width of not less than one mile for the circumscribing area of Class I projects and one-half mile for the circumscribing area of Class II and III projects. (b) However, in lieu...

40 CFR 147.3106 - Area of review.

Code of Federal Regulations, 2012 CFR

2012-07-01

... chapter, the fixed radius shall be no less than one mile for Class I wells and one-half mile for Class II... under § 146.6(b) shall be a fixed width of not less than one mile for the circumscribing area of Class I projects and one-half mile for the circumscribing area of Class II and III projects. (b) However, in lieu...

40 CFR 147.3106 - Area of review.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chapter, the fixed radius shall be no less than one mile for Class I wells and one-half mile for Class II... under § 146.6(b) shall be a fixed width of not less than one mile for the circumscribing area of Class I projects and one-half mile for the circumscribing area of Class II and III projects. (b) However, in lieu...

25 CFR 290.11 - May an Indian tribe distribute per capita payments from net gaming revenues derived from either...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false May an Indian tribe distribute per capita payments from net gaming revenues derived from either Class II or Class III gaming without a tribal revenue... net gaming revenues derived from either Class II or Class III gaming without a tribal revenue...

Arabidopsis Class I and Class II TCP Transcription Factors Regulate Jasmonic Acid Metabolism and Leaf Development Antagonistically1[C][W

PubMed Central

Danisman, Selahattin; van der Wal, Froukje; Dhondt, Stijn; Waites, Richard; de Folter, Stefan; Bimbo, Andrea; van Dijk, Aalt DJ; Muino, Jose M.; Cutri, Lucas; Dornelas, Marcelo C.; Angenent, Gerco C.; Immink, Richard G.H.

2012-01-01

TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1 (TCP) transcription factors control developmental processes in plants. The 24 TCP transcription factors encoded in the Arabidopsis (Arabidopsis thaliana) genome are divided into two classes, class I and class II TCPs, which are proposed to act antagonistically. We performed a detailed phenotypic analysis of the class I tcp20 mutant, showing an increase in leaf pavement cell sizes in 10-d-old seedlings. Subsequently, a glucocorticoid receptor induction assay was performed, aiming to identify potential target genes of the TCP20 protein during leaf development. The LIPOXYGENASE2 (LOX2) and class I TCP9 genes were identified as TCP20 targets, and binding of TCP20 to their regulatory sequences could be confirmed by chromatin immunoprecipitation analyses. LOX2 encodes for a jasmonate biosynthesis gene, which is also targeted by class II TCP proteins that are under the control of the microRNA JAGGED AND WAVY (JAW), although in an antagonistic manner. Mutation of TCP9, the second identified TCP20 target, resulted in increased pavement cell sizes during early leaf developmental stages. Analysis of senescence in the single tcp9 and tcp20 mutants and the tcp9tcp20 double mutants showed an earlier onset of this process in comparison with wild-type control plants in the double mutant only. Both the cell size and senescence phenotypes are opposite to the known class II TCP mutant phenotype in JAW plants. Altogether, these results point to an antagonistic function of class I and class II TCP proteins in the control of leaf development via the jasmonate signaling pathway. PMID:22718775

Rational Design Synthesis and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases

DOE Office of Scientific and Technical Information (OSTI.GOV)

R Daher; M Coincon; M Fonvielle

2011-12-31

We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows Ki against class II Fbas from various pathogens in the nM range, with very highmore » selectivity (up to 105). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.« less

Highlights of the DNA cutters: a short history of the restriction enzymes

PubMed Central

Loenen, Wil A. M.; Dryden, David T. F.; Raleigh, Elisabeth A.; Wilson, Geoffrey G.; Murray, Noreen E.

2014-01-01

In the early 1950’s, ‘host-controlled variation in bacterial viruses’ was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine. PMID:24141096

Highlights of the DNA cutters: a short history of the restriction enzymes.

PubMed

Loenen, Wil A M; Dryden, David T F; Raleigh, Elisabeth A; Wilson, Geoffrey G; Murray, Noreen E

2014-01-01

In the early 1950's, 'host-controlled variation in bacterial viruses' was reported as a non-hereditary phenomenon: one cycle of viral growth on certain bacterial hosts affected the ability of progeny virus to grow on other hosts by either restricting or enlarging their host range. Unlike mutation, this change was reversible, and one cycle of growth in the previous host returned the virus to its original form. These simple observations heralded the discovery of the endonuclease and methyltransferase activities of what are now termed Type I, II, III and IV DNA restriction-modification systems. The Type II restriction enzymes (e.g. EcoRI) gave rise to recombinant DNA technology that has transformed molecular biology and medicine. This review traces the discovery of restriction enzymes and their continuing impact on molecular biology and medicine.

The Rj4 allele in soybean represses nodulation by chlorosis-inducing bradyrhizobia classified as DNA homology group II by antibiotic resistance profiles.

PubMed

Devine, T E; Kuykendall, L D; O'Neill, J J

1990-07-01

To determine the relationship between nodulation restriction by the Rj4 allele of soybean, rhizobitoxine-induced chlorosis, and taxonomic grouping of bradyrhizobia, 119 bradyrhizobial isolates were tested in Leonard jar culture for nodulation response and chlorosis induction. In addition to strain USDA 61, the strain originally reported as defining the Rj4 response, eight other isolates (i.e., USDA 62, 83, 94, 238, 252, 259, 260, and 340) were discovered to elicit the nodulation interdiction of the Rj4 allele. Only 16% of all the bradyrhizobial strains tested induced chlorosis, but seven of the nine strains (78%) interdicted by the Rj4 allele were chlorosis-inducing strains. Furthermore, in tests for antibiotic resistance profile, eight of the nine interdicted strains (89%) were classed in DNA homology group II. This evidence suggests that the Rj4 allele has a positive value to the host plant in shielding it from nodulation by certain chlorosis-inducing bradyrhizobia of a DNA homology group with impaired efficiency of nitrogen fixation with soybean.

HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.

PubMed

Djilali-Saiah, Idriss; Fakhfakh, Amin; Louafi, Hamida; Caillat-Zucman, Sophie; Debray, Dominique; Alvarez, Fernando

2006-12-01

Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P < 0.0001) among patients with both anti-LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P < 0.0001) with anti-LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.

Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response.

PubMed

Reichstetter, S; Ettinger, R A; Liu, A W; Gebe, J A; Nepom, G T; Kwok, W W

2000-12-15

The polyclonal nature of T cells expanding in an ongoing immune response results in a range of disparate affinities and activation potential. Recently developed human class II tetramers provide a means to analyze this diversity by direct characterization of the trimolecular TCR-peptide-MHC interaction in live cells. Two HSV-2 VP16(369-379)-specific, DQA1*0102/DQB1*0602 (DQ0602)-restricted T cell clones were compared by means of T cell proliferation assay and HLA-DQ0602 tetramer staining. These two clones were obtained from the same subject, but show different TCR gene usage. Clone 48 was 10-fold more sensitive to VP16(369-379) peptide stimulation than clone 5 as assayed by proliferation assays, correlating with differences in MHC tetramer binding. Clone 48 gave positive staining with the DQ0602/VP16(369-379) tetramer at either 23 or 37 degrees C. Weak staining was also observed at 4 degrees C. Clone 5 showed weaker staining compared with clone 48 at 37 degrees C, and no staining was observed at 23 degrees C or on ice. Receptor internalization was not required for positive staining. Competitive binding indicates that the cell surface TCR of clone 48 has higher affinity for the DQ0602/VP16(369-379) complex than clone 5. The higher binding affinity of clone 48 for the peptide-MHC complex also correlates with a slower dissociation rate compared with clone 5.

WASp-dependent actin cytoskeleton stability at the dendritic cell immunological synapse is required for extensive, functional T cell contacts.

PubMed

Malinova, Dessislava; Fritzsche, Marco; Nowosad, Carla R; Armer, Hannah; Munro, Peter M G; Blundell, Michael P; Charras, Guillaume; Tolar, Pavel; Bouma, Gerben; Thrasher, Adrian J

2016-05-01

The immunological synapse is a highly structured and molecularly dynamic interface between communicating immune cells. Although the immunological synapse promotes T cell activation by dendritic cells, the specific organization of the immunological synapse on the dendritic cell side in response to T cell engagement is largely unknown. In this study, confocal and electron microscopy techniques were used to investigate the role of dendritic cell actin regulation in immunological synapse formation, stabilization, and function. In the dendritic cell-restricted absence of the Wiskott-Aldrich syndrome protein, an important regulator of the actin cytoskeleton in hematopoietic cells, the immunological synapse contact with T cells occupied a significantly reduced surface area. At a molecular level, the actin network localized to the immunological synapse exhibited reduced stability, in particular, of the actin-related protein-2/3-dependent, short-filament network. This was associated with decreased polarization of dendritic cell-associated ICAM-1 and MHC class II, which was partially dependent on Wiskott-Aldrich syndrome protein phosphorylation. With the use of supported planar lipid bilayers incorporating anti-ICAM-1 and anti-MHC class II antibodies, the dendritic cell actin cytoskeleton organized into recognizable synaptic structures but interestingly, formed Wiskott-Aldrich syndrome protein-dependent podosomes within this area. These findings demonstrate that intrinsic dendritic cell cytoskeletal remodeling is a key regulatory component of normal immunological synapse formation, likely through consolidation of adhesive interaction and modulation of immunological synapse stability. © The Author(s).

Comparison of Maxilla Mandibular Transverse Ratios With Class II Anteroposterior Discrepancies

DTIC Science & Technology

2014-03-20

the structure points has shown to be at best unreliable (Jacobson 1995). “2D landmarks may be hindered by rotational, geometric , and head positioning...deficiency in Class II and Class III malocclusions: a cephalometric and morphometric study on postero‐ anterior films. Orthodontics & Craniofacial

Prevalence of vulvovaginitis and relation to physical findings in girls assessed for suspected child sexual abuse.

PubMed

Rahman, Gisel; Ocampo, Dolores; Rubinstein, Anahí; Risso, Paula

2015-10-01

The presence of sexually transmitted infections (STIs) in patients with suspected sexual abuse is uncommon in the field of pediatrics. To establish the prevalence of anogenital findings and their relation to the presence of STIs in girls referred for suspected child sexual abuse. Retrospective study conducted between January 1st, 2003 and December 31st, 2013. Physical findings and detection of STIs in girls with suspected child sexual abuse were analyzed. One thousand thirty-four patients were included. Their median age was 7.9 years old. Anogenital findings were classified as class I (normal):38.4%, class II (nonspecific):38.1%, class III (specific):19.9% and class IV (definitive):3.6%. STIs were observed in 42 patients (4.1%). A relation was established between STIs and the classification of physical findings: 10 (class II: 9; class III: 1) Neisseria gonorrhoeae, 17 (class I: 2; class II: 8; class III: 7) Chlamydia trachomatis, 15 (class I: 2; class II: 10; class III: 3) Trichomonas vaginalis. Statistically significant differences for Trichomonas vaginalis (p= 0.01) and Neisseria gonorrhoeae (p < 0.0001) were observed, with predominance of nonspecific clinical signs. Both nonspecific and specific findings were similarly observed for Chlamydia trachomatis (p= 0.03). Most cases of girls with suspected child sexual abuse had normal or nonspecific anogenital findings. The prevalence of STIs in these girls is low. Trichomonas vaginalis and Neisseria gonorrhoeae were related to nonspecific findings, while both nonspecific and specific findings were observed for Chlamydia trachomatis.

Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

PubMed

Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

2005-01-01

Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

14 CFR 61.107 - Flight proficiency.

Code of Federal Regulations, 2010 CFR

2010-01-01

...-engine class rating: (i) Preflight preparation; (ii) Preflight procedures; (iii) Airport and seaplane... lighter-than-air category rating with an airship class rating: (i) Preflight preparation; (ii) Preflight...

14 CFR 61.107 - Flight proficiency.

Code of Federal Regulations, 2013 CFR

2013-01-01

...-engine class rating: (i) Preflight preparation; (ii) Preflight procedures; (iii) Airport and seaplane... lighter-than-air category rating with an airship class rating: (i) Preflight preparation; (ii) Preflight...

14 CFR 61.107 - Flight proficiency.

Code of Federal Regulations, 2012 CFR

2012-01-01

...-engine class rating: (i) Preflight preparation; (ii) Preflight procedures; (iii) Airport and seaplane... lighter-than-air category rating with an airship class rating: (i) Preflight preparation; (ii) Preflight...

14 CFR 61.107 - Flight proficiency.

Code of Federal Regulations, 2011 CFR

2011-01-01

...-engine class rating: (i) Preflight preparation; (ii) Preflight procedures; (iii) Airport and seaplane... lighter-than-air category rating with an airship class rating: (i) Preflight preparation; (ii) Preflight...

14 CFR 61.107 - Flight proficiency.

Code of Federal Regulations, 2014 CFR

2014-01-01

...-engine class rating: (i) Preflight preparation; (ii) Preflight procedures; (iii) Airport and seaplane... lighter-than-air category rating with an airship class rating: (i) Preflight preparation; (ii) Preflight...

The genetic origin of minor histocompatibility antigens.

PubMed

Roopenian, D C; Christianson, G J; Davis, A P; Zuberi, A R; Mobraaten, L E

1993-01-01

The purpose of this study was to elucidate the genetic origin of minor histocompatibility (H) antigens. Toward this end common inbred mouse strains, distinct subspecies, and species of the subgenus Mus were examined for expression of various minor H antigens. These antigens were encoded by the classical minor H loci H-3 and H-4 or by newly identified minor H antigens detected as a consequence of mutation. Both minor H antigens that stimulate MHC class I-restricted cytotoxic T cells (Tc) and antigens that stimulate MHC class II-restricted helper T cells (Th) were monitored. The results suggested that strains of distinct ancestry commonly express identical or cross-reactive antigens. Moreover, a correlation between the lack of expression of minor H antigens and ancestral heritage was observed. To address whether the antigens found on unrelated strains were allelic with the sensitizing minor H antigens or a consequence of antigen cross-reactivity, classical genetic segregation analysis was carried out. Even in distinct subspecies and species, the minor H antigens always mapped to the site of the appropriate minor H locus. Together the results suggest: 1) minor H antigen sequences are evolutionarily stable in that their pace of antigenic change is slow enough to predate subspeciation and speciation; 2) the minor H antigens originated in the inbred strains as a consequence of a rare polymorphism or loss mutation carried in a founder mouse stock that caused the mouse to perceive the wild-type protein as foreign; 3) there is a remarkable lack of antigenic cross-reactivity between the defined minor H antigens and other gene products.

Active site loop dynamics of a class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis

PubMed Central

Pegan, Scott D.; Rukseree, Kamolchanok; Capodagli, Glenn C.; Baker, Erica A; Krasnykh, Olga; Franzblau, Scott G; Mesecar, Andrew D

2014-01-01

Class II fructose 1,6-bisphosphate aldolases (FBA; E.C. 4.1.2.13) comprise one of two families of aldolases. Instead of forming a Schiff-base intermediate using an ε-amino group of a lysine side chain, class II FBAs utilize Zn(II) to stabilize a proposed hydroxyenolate intermediate (HEI) in the reversible cleavage of fructose 1,6-bisphosphate forming glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). As class II FBAs has been shown to be essential in pathogenic bacteria, focus has been placed on these enzymes as potential antibacterial targets. Although structural studies on class II FBAs from Mycobacterium tuberculosis (MtFBA), other bacteria and protozoa have been reported, the structure of the active site loop responsible for catalyzing the protonation/deprotonation steps of the reaction for class II FBAs has not yet been observed. We therefore utilized the potent class II FBA inhibitor phosphoglycolohydroxamate (PGH) as a mimic of the HEI/DHAP bound form of the enzyme and determined the X-ray structure of MtFBA-PGH complex to 1.58 Å. Remarkably, we are able to observe well-defined electron density for the previously elusive active site loop of MtFBA trapped in a catalytically competent orientation. Utilization of this structural information plus site-directed mutagenesis and kinetic studies conducted on a series of residues within the active-site loop revealed that E169 facilitates a water mediated deprotonation/protonation step of the MtFBA reaction mechanism. Also, secondary isotope effects on MtFBA and catalytically relevant mutants were used to probe the effect of loop flexibility on catalytic efficiency. Additionally, we also reveal the structure of MtFBA in its holoenzyme form. PMID:23298222

Antigenicity of mesenchymal stem cells in an inflamed joint environment.

PubMed

Hill, Jacqueline A; Cassano, Jennifer M; Goodale, Margaret B; Fortier, Lisa A

2017-07-01

OBJECTIVE To determine whether major histocompatability complex (MHC) class II expression in equine mesenchymal stem cells (MSCs) changes with exposure to a proinflammatory environment reflective of an inflamed joint. SAMPLE Cryopreserved bone marrow-derived MSCs from 12 horses and cartilage and synovium samples from 1 horse euthanized for reasons other than lameness. PROCEDURES In part 1 of a 3-part study, the suitability of a quantitative reverse transcriptase PCR (qRT-PCR) assay for measurement of MHC class II expression in MSCs following stimulation with interferon (IFN)-γ was assessed. In part 2, synoviocyte-cartilage cocultures were or were not stimulated with interleukin (IL)-1β (10 ng/mL) to generate conditioned media that did and did not (control) mimic an inflamed joint environment. In part 3, a qRT-PCR assay was used to measure MSC MHC class II expression after 96 hours of incubation with 1 of 6 treatments (control-conditioned medium, IL-1β-conditioned medium, and MSC medium alone [untreated control] or with IL-1β [10 ng/mL], tumor necrosis factor-α [10 ng/mL], or IFN-γ [100 ng/mL]). RESULTS The qRT-PCR assay accurately measured MHC class II expression. Compared with MHC class II expression for MSCs exposed to the untreated control medium, that for MSCs exposed to IL-1β was decreased, whereas that for MSCs exposed to IFN-γ was increased. Neither the control-conditioned nor tumor necrosis factor-α medium altered MHC class II expression. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MSC exposure to proinflammatory cytokine IL-1β decreased MHC class II expression and antigenicity. Treatment of inflamed joints with allogeneic MSCs might not be contraindicated, but further investigation is warranted.

IL-10-dependent down-regulation of MHC class II expression level on monocytes by peritoneal fluid from endometriosis patients.

PubMed

Lee, Kyu-Sup; Baek, Dae-Won; Kim, Ki-Hyung; Shin, Byoung-Sub; Lee, Dong-Hyung; Kim, Ja-Woong; Hong, Young-Seoub; Bae, Yoe-Sik; Kwak, Jong-Young

2005-11-01

Endometriosis is a gynecologic disorder characterized by the ectopic growth of misplaced endometrial cells. Moreover, immunological abnormalities of cell-mediated and humoral immunity may be associated with the pathogenesis of endometriosis. The effects of peritoneal fluid (PF) from endometriosis patients on the expression levels of MHC class II and costimulatory molecules on the cell surfaces of monocytes were investigated. Compared to the PF of controls, the addition of 10% PF (n=10) from patients with endometriosis to culture medium significantly reduced the percentage of MHC class II-positive cells in cultures of a THP-1, monocytic cell line at 48 h. The effect of endometriosis patient PF (EPF) was dose-dependent, and similar effect was observed in peripheral blood monocytes. An inverse correlation was found between MHC class II expression level and IL-10 concentration in EPF (r=-0.518; p=0.019) and in the supernatant of peripheral blood monocyte cultured in EPF (r=-0.459; p=0.042) (n=20). The expression levels of costimulatory molecules (CD80 and CD86), but not of CD54 and B7-H1, were down-regulated by EPF. The mRNA level of HLA-DR was unaffected by EPF but protein level was reduced by EPF. Neutralizing IL-10 antibody abrogated MHC class II down-regulation on monocytes, which had been induced by EPF. However, in a functional assay, monocytes treated with EPF failed to stimulate T cell in mixed leukocyte reaction, although T cell proliferation was increased with EPF-treated monocytes and Staphylococcus enterotoxin B. These results suggest that MHC class II expression level on monocytes is down-regulated by EPF, but the cell stimulatory ability of monocytes does not coincide with MHC class II expression level.

Active site loop dynamics of a class IIa fructose 1,6-bisphosphate aldolase from Mycobacterium tuberculosis.

PubMed

Pegan, Scott D; Rukseree, Kamolchanok; Capodagli, Glenn C; Baker, Erica A; Krasnykh, Olga; Franzblau, Scott G; Mesecar, Andrew D

2013-02-05

Class II fructose 1,6-bisphosphate aldolases (FBAs, EC 4.1.2.13) comprise one of two families of aldolases. Instead of forming a Schiff base intermediate using an ε-amino group of a lysine side chain, class II FBAs utilize Zn(II) to stabilize a proposed hydroxyenolate intermediate (HEI) in the reversible cleavage of fructose 1,6-bisphosphate, forming glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). As class II FBAs have been shown to be essential in pathogenic bacteria, focus has been placed on these enzymes as potential antibacterial targets. Although structural studies of class II FBAs from Mycobacterium tuberculosis (MtFBA), other bacteria, and protozoa have been reported, the structure of the active site loop responsible for catalyzing the protonation-deprotonation steps of the reaction for class II FBAs has not yet been observed. We therefore utilized the potent class II FBA inhibitor phosphoglycolohydroxamate (PGH) as a mimic of the HEI- and DHAP-bound form of the enzyme and determined the X-ray structure of the MtFBA-PGH complex to 1.58 Å. Remarkably, we are able to observe well-defined electron density for the previously elusive active site loop of MtFBA trapped in a catalytically competent orientation. Utilization of this structural information and site-directed mutagenesis and kinetic studies conducted on a series of residues within the active site loop revealed that E169 facilitates a water-mediated deprotonation-protonation step of the MtFBA reaction mechanism. Also, solvent isotope effects on MtFBA and catalytically relevant mutants were used to probe the effect of loop flexibility on catalytic efficiency. Additionally, we also reveal the structure of MtFBA in its holoenzyme form.

MHC Class II Activation and Interferon-γ Mediate the Inhibition of Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA).

PubMed

Ferreira-Duarte, Ana P; Pinheiro-Torres, Anelize S; Anhê, Gabriel F; Condino-Neto, Antônio; Antunes, Edson; DeSouza, Ivani A

2017-01-01

Staphylococcal enterotoxins are classified as superantigens that act by linking T-cell receptor with MHC class II molecules, which are expressed on classical antigen-presenting cells (APC). Evidence shows that MHC class II is also expressed in neutrophils and eosinophils. This study aimed to investigate the role of MHC class II and IFN-γ on chemotactic and adhesion properties of neutrophils and eosinophils after incubation with SEA. Bone marrow (BM) cells obtained from BALB/c mice were resuspended in culture medium, and incubated with SEA (3-30 ng/ml; 1-4 h), after which chemotaxis and adhesion were evaluated. Incubation with SEA significantly reduced the chemotactic and adhesive responses in BM neutrophils activated with IL-8 (200 ng/ml). Likewise, SEA significantly reduced the chemotactic and adhesive responses of BM eosinophils activated with eotaxin (300 ng/ml). The inhibitory effects of SEA on cell chemotaxis and adhesion were fully prevented by prior incubation with an anti-MHC class II blocking antibody (2 μg/ml). SEA also significantly reduced the intracellular Ca 2+ levels in IL-8- and eotaxin-activated BM cells. No alterations of MAC-1, VLA4, and LFA-1α expressions were observed after SEA incubation. In addition, SEA elevated by 3.5-fold ( P < 0.05) the INF-γ levels in BM cells. Incubation of BM leukocytes with IFN-γ (10 ng/ml, 2 h) reduced both neutrophil and eosinophil chemotaxis and adhesion, which were prevented by prior incubation with anti-MHC class II antibody (2 μg/ml). In conclusion, SEA inhibits neutrophil and eosinophil by MHC class II-dependent mechanism, which may be modulated by concomitant release of IFN-γ.

Active Site Loop Dynamics of a Class IIa Fructose 1,6-Bisphosphate Aldolase from Mycobacterium tuberculosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pegan, Scott D.; Rukseree, Kamolchanok; Capodagli, Glenn C.

The class II fructose 1,6-bisphosphate aldolases (FBAs, EC 4.1.2.13) comprises one of two families of aldolases. Instead of forming a Schiff base intermediate using an ε-amino group of a lysine side chain, class II FBAs utilize Zn(II) to stabilize a proposed hydroxyenolate intermediate (HEI) in the reversible cleavage of fructose 1,6-bisphosphate, forming glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). As class II FBAs have been shown to be essential in pathogenic bacteria, focus has been placed on these enzymes as potential antibacterial targets. Although structural studies of class II FBAs from Mycobacterium tuberculosis (MtFBA), other bacteria, and protozoa have been reported,more » the structure of the active site loop responsible for catalyzing the protonation–deprotonation steps of the reaction for class II FBAs has not yet been observed. We therefore utilized the potent class II FBA inhibitor phosphoglycolohydroxamate (PGH) as a mimic of the HEI- and DHAP-bound form of the enzyme and determined the X-ray structure of the MtFBA–PGH complex to 1.58 Å. Remarkably, we are able to observe well-defined electron density for the previously elusive active site loop of MtFBA trapped in a catalytically competent orientation. Utilization of this structural information and site-directed mutagenesis and kinetic studies conducted on a series of residues within the active site loop revealed that E169 facilitates a water-mediated deprotonation–protonation step of the MtFBA reaction mechanism. Furthermore, solvent isotope effects on MtFBA and catalytically relevant mutants were used to probe the effect of loop flexibility on catalytic efficiency. Additionally, we also reveal the structure of MtFBA in its holoenzyme form.« less

Intercellular Transfer of a Soluble Viral Superantigen

PubMed Central

Reilly, Melissa; Mix, Denise; Reilly, Andrew A.; Yang Ye, Xiang; Winslow, Gary M.

2000-01-01

Mouse mammary tumor virus (MMTV) superantigens (vSAgs) can undergo intercellular transfer in vivo and in vitro such that a vSAg can be presented to T cells by major histocompatibility complex (MHC) class II proteins on antigen-presenting cells (APCs) that do not express the superantigen. This process may allow T-cell activation to occur prior to viral infection. Consistent with these findings, vSAg produced by Chinese hamster ovary (CHO) cells was readily transferred to class II IE and IA (H-2k and H-2d) proteins on a B-cell lymphoma or mouse splenocytes. Fixed class II-expressing acceptor cells were used to demonstrate that the vSAg, but not the class II proteins, underwent intercellular transfer, indicating that vSAg binding to class II MHC could occur directly at the cell surface. Intercellular transfer also occurred efficiently to splenocytes from endogenous retrovirus-free mice, indicating that other proviral proteins were not involved. Presentation of vSAg7 produced by a class II-negative, furin protease-deficient CHO variant (FD11) was unsuccessful, indicating that proteolytic processing was a requisite event and that proteolytic activity could not be provided by an endoprotease on the acceptor APC. Furthermore, vSAg presentation was effected using cell-free supernatant from class II-negative, vSAg-positive cells, indicating that a soluble molecule, most likely produced by proteolytic processing, was sufficient to stimulate T cells. Because the membrane-proximal endoproteolytic cleavage site in the vSAg (residues 68 to 71) was not necessary for intercellular transfer, the data support the notion that the carboxy-terminal endoproteolytic cleavage product is an active vSAg moiety. PMID:10954523

Dentoskeletal modifications in Class II deep bite malocclusion treatment with anterior bite plane functional appliance

PubMed Central

Ciavarella, Domenico; Laurenziello, Michele; Guida, Laura; Montaruli, Graziano; Gallo, Crescenzio; Lo Muzio, Lorenzo

2017-01-01

Background A treatment modality for Class II division 1 malocclusion is discussed. Orthodontic treatment of patients with deep bite and Class II malocclusion is an important challenge in clinical practice. The aim of this work is to compare the efficacy of anterior bite plane functional appliance (ABPFA) by assessing the changes in different times with untreated patients by literature. Material and Methods The study group comprised 22 subjects with Class II division 1 malocclusion and hypo-divergent. Eligibility criteria for this study were: dental Class II division 1 malocclusion, hypo-divergent skeletal pattern, late mixed or permanent dentition. We analyzed with the use of stable bone structure (ASCB) at two different times: pre-treatment (T0) and post-treatment (T1) after 24 months. Inter-group differences were evaluated with paired samples t-test at the P<0.05 level. Results No statistical significant differences were found in cephalometric skeletal measurements, whereas dental parameters showed a significant different overjet, which was significantly reduced (6 mm at T0 vs. 5 mm at T1) in our series. Conclusions In ABPFA group, the treatment effects were reduce mainly Class II malocclusion, overjet and overbite alteration. This appliance seems to suggest a significant beneficial effect in mandible displacement by reducing the counter clockwise rotation of the mandible, which is further confirmed by the almost absence of modifications of ArGoMe and SNGoMe angles. The ABPFA is particularly suitable to reduce the non-desirable dental effects represented by lower incisors pro inclination, and upper incisors retro-inclination. Key words:Orthodontics, Functional orthodontics, Class II malocclusion, Anterior bite plane functional appliance. PMID:28936295

18 CFR 415.21 - Class II projects.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Class II projects. 415.21 Section 415.21 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-FLOOD PLAIN REGULATIONS Types of Projects and Jurisdiction § 415.21 Class...

78 FR 36698 - Microbiology Devices; Reclassification of Nucleic Acid-Based Systems for Mycobacterium tuberculosis

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... specimens from class III (premarket approval) into class II (special controls). FDA is also issuing the draft special controls guideline entitled ``Class II Special Controls Guideline: Nucleic Acid-Based In... regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three...

Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

PubMed Central

Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

2012-01-01

Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

The Bacillus subtilis ywjI (glpX) gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the class III Fbp enzyme.

PubMed

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-05-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions.

The Bacillus subtilis ywjI (glpX) Gene Encodes a Class II Fructose-1,6-Bisphosphatase, Functionally Equivalent to the Class III Fbp Enzyme▿

PubMed Central

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-01-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions. PMID:19270101

Correcting for Indirect Range Restriction in Meta-Analysis: Testing a New Meta-Analytic Procedure

ERIC Educational Resources Information Center

Le, Huy; Schmidt, Frank L.

2006-01-01

Using computer simulation, the authors assessed the accuracy of J. E. Hunter, F. L. Schmidt, and H. Le's (2006) procedure for correcting for indirect range restriction, the most common type of range restriction, in comparison with the conventional practice of applying the Thorndike Case II correction for direct range restriction. Hunter et…

Curve of Spee and its relationship to vertical eruption of teeth among different malocclusion groups.

PubMed

Veli, Ilknur; Ozturk, Mehmet Ali; Uysal, Tancan

2015-03-01

Our objectives were to assess the depth of the curve of Spee (COS) in different malocclusion groups, to relate this to the eruption of anterior or posterior teeth quantitatively, and to determine whether the depth of the COS is affected by the vertical eruption of anterior or posterior teeth. Two hundred conventional lateral cephalograms and 3-dimensional models of untreated patients (70 boys, mean age: 16.4 ± 1.4 years; 130 young women, mean age: 18.1 ± 1.8 years) were included and assigned to 4 malocclusion groups as Class I, Class II Division 1, Class II Division 2, and Class III. The depth of the COS, overjet, and overbite were measured on 3-dimensional models. The perpendicular distance between the incisal tip of the mandibular central incisor (L1-MP), the deepest point of the COS (S-MP), and the distobuccal cusp tip of the mandibular second molar (L7-MP) to the mandibular plane were calculated and proportioned with each other. The Pearson correlation coefficient was calculated, and multiple linear regression analysis was carried out. Also, multivariate analysis of variance was performed at the P <0.05 level. The mesiobuccal cusp of the first molar was the deepest part of the COS in all groups, with a maximum depth of 2.44 ± 0.73 mm in the Class II Division 1 subjects and a minimum depth of 1.76 ± 0.94 in the Class III subjects. The depth of the COS changed as follows: Class II Division 1 > Class II Division 2 > Class I > Class III malocclusion groups. Statistically significant positive correlations were found between the depth of the COS and L1-MP/S-MP (r = 0.541) and L7-MP/S-MP (r = 0.269) in the Class I and Class III subjects, and between the depth of the COS and overjet (r = 0.483) and L7-MP/S-MP (r = 0.289) in the Class II Division 1 subjects. All variables except overjet had positive correlations with the depth of the COS in Class II Division 2 subjects. The multivariate analysis of variance showed statistically significant differences in overjet, overbite, L1-MP/S-MP, L7-MP/S-MP, and the depth of the COS (P <0.001) among the groups. Although the overjet differed, vertical eruption of the anterior teeth did not differ among the different malocclusion groups and had a significant contribution to the depth of the COS in subjects with Class I and Class III malocclusions. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Biowaiver extension potential and IVIVC for BCS Class II drugs by formulation design: Case study for cyclosporine self-microemulsifying formulation.

PubMed

Yang, Su-Geun

2010-11-01

The objective of this work was to suggest the biowaiver potential of biopharmaceutical classification system (BCS) Class II drugs in self-microemulsifying drug delivery systems (SMEDDS) which are known to increase the solubility, dissolution and oral absorption of water-insoluble drugs. Cyclosporine was selected as a representative BCS Class II drug. New generic candidate of cyclosporine SMEDDS (test) was applied for the study with brand SMEDDS (reference I) and cyclosporine self-emulsifying drug delivery systems (SEDDS, reference II). Solubility and dissolution of cyclosporine from SMEDDS were critically enhanced, which were the similar behaviors with BCS class I drug. The test showed the identical dissolution rate and the equivalent bioavailability (0.34, 0.42 and 0.68 of p values for AUC₀(→)₂₄(h), C(max) and T(max), respectively) with the reference I. Based on the results, level A in vitro-in vivo correlation (IVIVC) was established from these two SMEDDS formulations. This study serves as a good example for speculating the biowaiver extension potential of BCS Class II drugs specifically in solubilizing formulation such as SMEDDS.

A Cephalometric Comparison of Twin Block and Bionator Appliances in Treatment of Class II Malocclusion

PubMed Central

Ahmadian-Babaki, Fatemeh; Araghbidi-Kashani, S. Mehdi

2017-01-01

Background Class II malocclusion is one of the most common orthodontic problems. In cases of class II malocclusion with mandibular deficiency, functional appliances often are used with the intent of stimulating mandibular growth. Bionator and twin block are two of the more popular functional appliances. The aim of this study was to compare the treatment outcomes of these two appliances using cephalometric radiographs. Material and Methods Cephalometric radiographs of 33 patients who had class II division I malocclusion, before and after treatment were digitalized. The mean changes in twin block and bionator groups were compared using independent t test. Results Twin block and bionator showed no statistically significant differences in cephalometric parameters except for ANB, NA-Pog, Basal and Ar-Go-Me angles. Conclusions There were no statistically significant differences in dentoalveolar and mandibular position between twin block and bionator (p>0.1). Twin block was more efficient in inhibition of forward movement of maxilla (p<0.1). Key words:Functional, Class II malocclusion, Cephalometrics, Twin block, Bionator, Treatment. PMID:28149473

37 GHz Methanol Masers : Horsemen of the Apocalypse for the Class II Methanol Maser Phase?

NASA Astrophysics Data System (ADS)

Ellingsen, S. P.; Breen, S. L.; Sobolev, A. M.; Voronkov, M. A.; Caswell, J. L.; Lo, N.

2011-12-01

We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

A research for Class II defect Bored Pile’s Accept Criteria: A case of Penang Second Marine bridge

NASA Astrophysics Data System (ADS)

Huang, Kang

2018-03-01

The aim of this preliminary research is to study the accept criteria of class II bored pile with subtle defect. According to a detailed comparison of the existed different standards, Chinese ones are more applicable especially for the large diameter bored piles. Through the concrete coring at pile No P25-03 of this case and the comparison to the actual calculation, the Class II pile’s defects were very minor. Comparison was also made for the effects on pile structural capacities before and after repair of the defects. the feasible repair proposal may bring forward to more defects to the piles. The Class II piles don’t need any further repairation when piles have typical of similar character and sonic logging test result with P25-03‘s one. For other Class II piles with some differences in characters, verification is needed through further concrete coring on the pile. The recommendation of this research could be adopted for the similar huge marine structures which installed large diameter bored piles.

Functional Interaction between Class II Histone Deacetylases and ICP0 of Herpes Simplex Virus Type 1

PubMed Central

Lomonte, Patrick; Thomas, Joëlle; Texier, Pascale; Caron, Cécile; Khochbin, Saadi; Epstein, Alberto L.

2004-01-01

This study describes the physical and functional interactions between ICP0 of herpes simplex virus type 1 and class II histone deacetylases (HDACs) 4, 5, and 7. Class II HDACs are mainly known for their participation in the control of cell differentiation through the regulation of the activity of the transcription factor MEF2 (myocyte enhancer factor 2), implicated in muscle development and neuronal survival. Immunofluorescence experiments performed on transfected cells showed that ICP0 colocalizes with and reorganizes the nuclear distribution of ectopically expressed class I and II HDACs. In addition, endogenous HDAC4 and at least one of its binding partners, the corepressor protein SMRT (for silencing mediator of retinoid and thyroid receptor), undergo changes in their nuclear distribution in ICP0-transfected cells. As a result, during infection endogenous HDAC4 colocalizes with ICP0. Coimmunoprecipitation and glutathione S-transferase pull-down assays confirmed that class II but not class I HDACs specifically interacted with ICP0 through their amino-terminal regions. This region, which is not conserved in class I HDACs but homologous to the MITR (MEF2-interacting transcription repressor) protein, is responsible for the repression, in a deacetylase-independent manner, of MEF2 by sequestering it under an inactive form in the nucleus. Consequently, we show that ICP0 is able to overcome the HDAC5 amino-terminal- and MITR-induced MEF2A repression in gene reporter assays. This is the first report of a viral protein interacting with and controlling the repressor activity of class II HDACs. We discuss the putative consequences of such an interaction for the biology of the virus both during lytic infection and reactivation from latency. PMID:15194749

21 CFR 809.30 - Restrictions on the sale, distribution and use of analyte specific reagents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Restrictions on the sale, distribution and use of... Requirements for Manufacturers and Producers § 809.30 Restrictions on the sale, distribution and use of analyte... include the statement for class I exempt ASR's: “Analyte Specific Reagent. Analytical and performance...

40 CFR 82.70 - Nonessential Class II products and exceptions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... provide for motor vehicle safety in accordance with Federal Motor Vehicle Safety Standards until January 1... 21 CFR 2.125(e); (ii) Lubricants, coatings or cleaning fluids for electrical or electronic equipment...; (iii) Lubricants, coatings or cleaning fluids used for aircraft maintenance, which contain class II...

Cheetah paradigm revisited: MHC diversity in the world's largest free-ranging population.

PubMed

Castro-Prieto, Aines; Wachter, Bettina; Sommer, Simone

2011-04-01

For more than two decades, the cheetah (Acinonyx jubatus) has been considered a paradigm of disease vulnerability associated with low genetic diversity, particularly at the immune genes of the major histocompatibility complex (MHC). Cheetahs have been used as a classic example in numerous conservation genetics textbooks as well as in many related scientific publications. However, earlier studies used methods with low resolution to quantify MHC diversity and/or small sample sizes. Furthermore, high disease susceptibility was reported only for captive cheetahs, whereas free-ranging cheetahs show no signs of infectious diseases and a good general health status. We examined whether the diversity at MHC class I and class II-DRB loci in 149 Namibian cheetahs was higher than previously reported using single-strand conformation polymorphism analysis, cloning, and sequencing. MHC genes were examined at the genomic and transcriptomic levels. We detected ten MHC class I and four class II-DRB alleles, of which nine MHC class I and all class II-DRB alleles were expressed. Phylogenetic analyses and individual genotypes suggested that the alleles belong to four MHC class I and three class II-DRB putative loci. Evidence of positive selection was detected in both MHC loci. Our study indicated that the low number of MHC class I alleles previously observed in cheetahs was due to a smaller sample size examined. On the other hand, the low number of MHC class II-DRB alleles previously observed in cheetahs was further confirmed. Compared with other mammalian species including felids, cheetahs showed low levels of MHC diversity, but this does not seem to influence the immunocompetence of free-ranging cheetahs in Namibia and contradicts the previous conclusion that the cheetah is a paradigm species of disease vulnerability.

Genotypic analysis of strains of mutans streptococci by pulsed-field gel electrophoresis.

PubMed

Mineyama, R; Yoshino, S; Fukushima, K

2004-01-01

The species and serotypes of various strains of S. mutans and S. sobrinus were characterized by pulsed-field gel electrophoresis after the genomic DNA from the various strains had been digested with five restriction enzymes (EcoR I, Xba I, Hind III, Sfi I and BssH II) separately. Among these restriction enzymes, BssH II was very useful for the characterization of species and serotypes and, in particular, digestion discriminated between serotypes d and g. The restriction patterns obtained from the genomic DNA of isolates isolated from children's saliva were essentially identical to those from the genomic DNA of the standard laboratory strains. Patterns of BssH II digests of the genomic DNA of 10 isolates identified as S. sobrinus were characteristic of serotype g of the standard laboratory strains. Our results indicate that digestion with BssH II and subsequence analysis by pulsed-field gel electrophoresis should be useful for the characterization of species and serotypes and for epidemiological studies of mutans streptococci.

Lateral-access Class II restoration using resin-modified glass-ionomer or silver-cermet cement.

PubMed

Croll, T P

1995-02-01

Direct-access preparation of a carious proximal surface is perhaps the most conservative approach to restoration. Physical properties and handling characteristics of silver amalgam and of resin composite and lack of fluoride ion release make these materials unsuitable for direct buccal- or lingual-access proximal restoration. Insufficient strengths and radiolucency of self-hardening glass-ionomer cements preclude their use for Class II restorations. However, glass-ionomer silver-cermet cement and some resin-modified glass-ionomer materials are proving useful for non-stress-bearing Class II restorations and may have applications in preventive dentistry. This article describes lateral-access Class II restoration with modified glass-ionomer cements. Emphasis is placed on careful handling of materials, maintenance of an ideal operative field, and conservation of tooth structure.

Characterization of full-length MHC class II sequences in Indonesian and Vietnamese cynomolgus macaques.

PubMed

Creager, Hannah M; Becker, Ericka A; Sandman, Kelly K; Karl, Julie A; Lank, Simon M; Bimber, Benjamin N; Wiseman, Roger W; Hughes, Austin L; O'Connor, Shelby L; O'Connor, David H

2011-09-01

In recent years, the use of cynomolgus macaques in biomedical research has increased greatly. However, with the exception of the Mauritian population, knowledge of the MHC class II genetics of the species remains limited. Here, using cDNA cloning and Sanger sequencing, we identified 127 full-length MHC class II alleles in a group of 12 Indonesian and 12 Vietnamese cynomolgus macaques. Forty two of these were completely novel to cynomolgus macaques while 61 extended the sequence of previously identified alleles from partial to full length. This more than doubles the number of full-length cynomolgus macaque MHC class II alleles available in GenBank, significantly expanding the allele library for the species and laying the groundwork for future evolutionary and functional studies.

Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of nucleobases in a precisely pre-determined sequence

PubMed Central

2011-01-01

Background Restriction endonucleases are widely applied in recombinant DNA technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of halogen nucleobases into DNA. This has been done for the purpose of anticancer radio- and phototherapy that is our long-term objective. Results An enzymatic method for synthesizing long double-stranded DNA labeled with the halogen derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and successfully tested on three different DNA fragments containing the 5-bromouracil (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain-Reaction (PCR) fragments containing two recognition sequences for the same or different class IIS restriction endonucleases, where each PCR fragment has a partially complementary cleavage site. These sites are introduced using synthetic DNA primers or are naturally present in the sequence used. The cleavage sites are not compatible, and therefore not susceptible to ligation until they are partially filled with a Hal-NB or original nucleobase, resulting in complementary cohesive end formation. Ligation of these fragments ultimately leads to the required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely long DNA fragment can be obtained by means of a multiple assembly reaction (n × maximum PCR product length: n × app. 50 kb). Conclusions The long, precisely labeled DNA duplexes obtained behave in very much the same manner as natural DNA and are beyond the range of chemical synthesis. Moreover, the conditions of synthesis closely resemble the natural ones, and all the artifacts accompanying the chemical synthesis of DNA are thus eliminated. The approach proposed seems to be completely general and could be used to label DNA at multiple pre-determined sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with Hal-NBs at specific position is an indispensable condition for the understanding and optimization of DNA photo- and radio-degradation, which are prerequisites for clinical trials of Hal-NBs in anticancer therapy. PMID:21864341

Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of nucleobases in a precisely pre-determined sequence.

PubMed

Sobolewski, Ireneusz; Polska, Katarzyna; Zylicz-Stachula, Agnieszka; Jeżewska-Frąckowiak, Joanna; Rak, Janusz; Skowron, Piotr

2011-08-24

Restriction endonucleases are widely applied in recombinant DNA technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of halogen nucleobases into DNA. This has been done for the purpose of anticancer radio- and phototherapy that is our long-term objective. An enzymatic method for synthesizing long double-stranded DNA labeled with the halogen derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and successfully tested on three different DNA fragments containing the 5-bromouracil (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain-Reaction (PCR) fragments containing two recognition sequences for the same or different class IIS restriction endonucleases, where each PCR fragment has a partially complementary cleavage site. These sites are introduced using synthetic DNA primers or are naturally present in the sequence used. The cleavage sites are not compatible, and therefore not susceptible to ligation until they are partially filled with a Hal-NB or original nucleobase, resulting in complementary cohesive end formation. Ligation of these fragments ultimately leads to the required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely long DNA fragment can be obtained by means of a multiple assembly reaction (n × maximum PCR product length: n × app. 50 kb). The long, precisely labeled DNA duplexes obtained behave in very much the same manner as natural DNA and are beyond the range of chemical synthesis. Moreover, the conditions of synthesis closely resemble the natural ones, and all the artifacts accompanying the chemical synthesis of DNA are thus eliminated. The approach proposed seems to be completely general and could be used to label DNA at multiple pre-determined sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with Hal-NBs at specific position is an indispensable condition for the understanding and optimization of DNA photo- and radio-degradation, which are prerequisites for clinical trials of Hal-NBs in anticancer therapy.

A peptide-binding motif for I-A(g7), the class II major histocompatibility complex (MHC) molecule of NOD and Biozzi AB/H mice.

PubMed

Harrison, L C; Honeyman, M C; Trembleau, S; Gregori, S; Gallazzi, F; Augstein, P; Brusic, V; Hammer, J; Adorini, L

1997-03-17

The class II major histocompatibility complex molecule I-A(g7) is strongly linked to the development of spontaneous insulin-dependent diabetes mellitus (IDDM) in non obese diabetic mice and to the induction of experimental allergic encephalomyelitis in Biozzi AB/H mice. Structurally, it resembles the HLA-DQ molecules associated with human IDDM, in having a non-Asp residue at position 57 in its beta chain. To identify the requirements for peptide binding to I-A(g7) and thereby potentially pathogenic T cell epitopes, we analyzed a known I-A(g7)-restricted T cell epitope, hen egg white lysozyme (HEL) amino acids 9-27. NH2- and COOH-terminal truncations demonstrated that the minimal epitope for activation of the T cell hybridoma 2D12.1 was M12-R21 and the minimum sequence for direct binding to purified I-A(g7) M12-Y20/K13-R21. Alanine (A) scanning revealed two primary anchors for binding at relative positions (p) 6 (L) and 9 (Y) in the HEL epitope. The critical role of both anchors was demonstrated by incorporating L and Y in poly(A) backbones at the same relative positions as in the HEL epitope. Well-tolerated, weakly tolerated, and nontolerated residues were identified by analyzing the binding of peptides containing multiple substitutions at individual positions. Optimally, p6 was a large, hydrophobic residue (L, I, V, M), whereas p9 was aromatic and hydrophobic (Y or F) or positively charged (K, R). Specific residues were not tolerated at these and some other positions. A motif for binding to I-A(g7) deduced from analysis of the model HEL epitope was present in 27/30 (90%) of peptides reported to be I-A(g7)-restricted T cell epitopes or eluted from I-A(g7). Scanning a set of overlapping peptides encompassing human proinsulin revealed the motif in 6/6 good binders (sensitivity = 100%) and 4/13 weak or non-binders (specificity = 70%). This motif should facilitate identification of autoantigenic epitopes relevant to the pathogenesis and immunotherapy of IDDM.

The relationship between Class I and Class II methanol masers at high angular resolution

NASA Astrophysics Data System (ADS)

McCarthy, T. P.; Ellingsen, S. P.; Voronkov, M. A.; Cimò, G.

2018-06-01

We have used the Australia Telescope Compact Array (ATCA) to make the first high-resolution observations of a large sample of class I methanol masers in the 95-GHz (80-71A+) transition. The target sources consist of a statistically complete sample of 6.7-GHz class II methanol masers with an associated 95-GHz class I methanol maser, enabling a detailed study of the relationship between the two methanol maser classes at arcsecond angular resolution. These sources have been previously observed at high resolution in the 36- and 44-GHz transitions, allowing comparison between all three class I maser transitions. In total, 172 95-GHz maser components were detected across the 32 target sources. We find that at high resolution, when considering matched maser components, a 3:1 flux density ratio is observed between the 95- and 44-GHz components, consistent with a number of previous lower angular resolution studies. The 95-GHz maser components appear to be preferentially located closer to the driving sources and this may indicate that this transition is more strongly inverted nearby to background continuum sources. We do not observe an elevated association rate between 95-GHz maser emission and more evolved sources, as indicated by the presence of 12.2-GHz class II masers. We find that in the majority of cases where both class I and class II methanol emission is observed, some component of the class I emission is associated with a likely outflow candidate.

Interstitial telomere-like repeats in the Arabidopsis thaliana genome.

PubMed

Uchida, Wakana; Matsunaga, Sachihiro; Sugiyama, Ryuji; Kawano, Shigeyuki

2002-02-01

Eukaryotic chromosomal ends are protected by telomeres, which are thought to play an important role in ensuring the complete replication of chromosomes. On the other hand, non-functional telomere-like repeats in the interchromosomal regions (interstitial telomeric repeats; ITRs) have been reported in several eukaryotes. In this study, we identified eight ITRs in the Arabidopsis thaliana genome, each consisting of complete and degenerate 300- to 1200-bp sequences. The ITRs were grouped into three classes (class IA-B, class II, and class IIIA-E) based on the degeneracy of the telomeric repeats in ITRs. The telomeric repeats of the two ITRs in class I were conserved for the most part, whereas the single ITR in class II, and the five ITRs in class III were relatively degenerated. In addition, degenerate ITRs were surrounded by common sequences that shared 70-100% homology to each other; these are named ITR-adjacent sequences (IAS). Although the genomic regions around ITRs in class I lacked IAS, those around ITRs in class II contained IAS (IASa), and those around five ITRs in class III had nine types of IAS (IASb, c, d, e, f, g, h, i, and j). Ten IAS types in classes II and III showed no significant homology to each other. The chromosomal locations of ITRs and IAS were not category-related, but most of them were adjacent to, or part of, a centromere. These results show that the A. thaliana genome has undergone chromosomal rearrangements, such as end-fusions and segmental duplications.

Treatment burden in patients with at least one class IV or V CFTR mutation.

PubMed

Dewulf, Jonas; Vermeulen, François; Wanyama, Simeon; Thomas, Muriel; Proesmans, Marijke; Dupont, Lieven; De Boeck, Kris

2015-12-01

CFTR mutations are grouped according to disease-causing mechanism. Several studies demonstrated that patients having at least one mutation of class IV/V, present with a milder phenotype, but little is known about their relative treatment burden. We compared treatment burden between patients with two class I, II, or III mutations and patients with at least one mutation of class IV/V in the 2010 database of the Belgian CF Registry. We calculated a "Treatment Burden Index" (TBI) by assigning long term therapies to categories low, medium and high intensity, for differential weighing in the total score. There were 779 patients with two known class I/II/III mutations and 94 patients with at least one class IV/V mutation. Compared to class I/II/III, class IV/V patients had a lower median number of clinic visits (4 vs. 5; P < 0.001), a lower risk of hospitalization (24.7% vs. 50.8%; P < 0.001) and intravenous antibiotic treatment (23.5% vs. 46.0%; P < 0.001) and a lower median TBI (6 vs. 9; P < 0.001). These differences remained significant when only class IV/V patients with pancreatic insufficiency (n = 31) were considered. This study clearly demonstrates the significantly lower treatment burden in patients with CF and at least one class IV/V mutation compared to patients with two class I/II/III mutations and contributes to providing better individual counseling at time of diagnosis. © 2015 Wiley Periodicals, Inc.

Treatment outcome of bimaxillary surgery for asymmetric skeletal class II deformity.

PubMed

Chen, Yun-Fang; Liao, Yu-Fang; Chen, Yin-An; Chen, Yu-Ray

2018-05-04

Facial asymmetry is one of the main concerns in patients with a dentofacial deformity. The aims of the study were to (1) evaluate the changes in facial asymmetry after bimaxillary surgery for asymmetric skeletal class II deformity and (2) compare preoperative and postoperative facial asymmetry of class II patients with normal controls. The facial asymmetry was assessed for 30 adults (21 women and 9 men, mean age: 29.3 years) who consecutively underwent bimaxillary surgery for asymmetric skeletal class II deformity using cone-beam computed tomography before and at least 6 months after surgery. Thirty soft tissue and two dental landmarks were identified on each three-dimensional facial image, and the asymmetry index of each landmark was calculated. Results were compared with those of 30 normal control subjects (21 women and 9 men, mean age: 26.2 years) with skeletal class I structure. Six months after surgery, the asymmetric index of the lower face and total face decreased significantly (17.8 ± 29.4 and 16.6 ± 29.5 mm, respectively, both p < 0.01), whereas the asymmetric index of the middle face increased significantly (1.2 ± 2.2 mm, p < 0.01). Postoperatively, 53% of the class II patients had residual chin asymmetry. The postoperative total face asymmetric index was positively correlated with the preoperative asymmetric index (r = 0.37, p < 0.05). Bimaxillary surgery for patients with asymmetric class II deformity resulted in a significant improvement in lower face asymmetry. However, approximately 50% of the patients still had residual chin asymmetry. The total face postoperative asymmetry was moderately related to the initial severity of asymmetry. These findings could help clinicians better understand orthognathic outcomes on different facial regions for patients with asymmetric class II deformity.

48 CFR 211.271 - Elimination of use of class I ozone-depleting substances.

Code of Federal Regulations, 2010 CFR

2010-10-01

... class I ozone-depleting substances. 211.271 Section 211.271 Federal Acquisition Regulations System... Using and Maintaining Requirements Documents 211.271 Elimination of use of class I ozone-depleting substances. See subpart 223.8 for restrictions on contracting for ozone-depleting substances. [70 FR 73150...

48 CFR 211.271 - Elimination of use of class I ozone-depleting substances.

Code of Federal Regulations, 2013 CFR

2013-10-01

... class I ozone-depleting substances. 211.271 Section 211.271 Federal Acquisition Regulations System... Using and Maintaining Requirements Documents 211.271 Elimination of use of class I ozone-depleting substances. See subpart 223.8 for restrictions on contracting for ozone-depleting substances. [70 FR 73150...

48 CFR 211.271 - Elimination of use of class I ozone-depleting substances.

Code of Federal Regulations, 2012 CFR

2012-10-01

... class I ozone-depleting substances. 211.271 Section 211.271 Federal Acquisition Regulations System... Using and Maintaining Requirements Documents 211.271 Elimination of use of class I ozone-depleting substances. See subpart 223.8 for restrictions on contracting for ozone-depleting substances. [70 FR 73150...

48 CFR 211.271 - Elimination of use of class I ozone-depleting substances.

Code of Federal Regulations, 2011 CFR

2011-10-01

... class I ozone-depleting substances. 211.271 Section 211.271 Federal Acquisition Regulations System... Using and Maintaining Requirements Documents 211.271 Elimination of use of class I ozone-depleting substances. See subpart 223.8 for restrictions on contracting for ozone-depleting substances. [70 FR 73150...

48 CFR 211.271 - Elimination of use of class I ozone-depleting substances.

Code of Federal Regulations, 2014 CFR

2014-10-01

... class I ozone-depleting substances. 211.271 Section 211.271 Federal Acquisition Regulations System... Using and Maintaining Requirements Documents 211.271 Elimination of use of class I ozone-depleting substances. See subpart 223.8 for restrictions on contracting for ozone-depleting substances. [70 FR 73150...

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection

PubMed Central

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D.; Ndung'u, Thumbi

2017-01-01

ABSTRACT Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. PMID:28077659

STAR FORMATION AND YOUNG POPULATION OF THE H II COMPLEX Sh2-294

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samal, M. R.; Pandey, A. K.; Chauhan, N.

The Sh2-294 H II region ionized by a single B0V star features several infrared excess sources, a photodissociation region, and also a group of reddened stars at its border. The star formation scenario in this region seems to be quite complex. In this paper, we present follow-up results of Sh2-294 H II region at 3.6, 4.5, 5.8, and 8.0 {mu}m observed with the Spitzer Space Telescope Infrared Array Camera (IRAC), coupled with H{sub 2} (2.12 {mu}m) observation, to characterize the young population of the region and to understand its star formation history. We identified 36 young stellar object (YSO, Classmore » I, Class II, and Class I/II) candidates using IRAC color-color diagrams. It is found that Class I sources are preferentially located at the outskirts of the H II region and associated with enhanced H{sub 2} emission; none of them are located near the central cluster. Combining the optical to mid-infrared (MIR) photometry of the YSO candidates and using the spectral energy distribution fitting models, we constrained stellar parameters and the evolutionary status of 33 YSO candidates. Most of them are interpreted by the model as low-mass (<4 M{sub Sun }) YSOs; however, we also detected a massive YSO ({approx}9 M{sub Sun }) of Class I nature, embedded in a cloud of visual extinction of {approx}24 mag. Present analysis suggests that the Class I sources are indeed a younger population of the region relative to Class II sources (age {approx} 4.5 Multiplication-Sign 10{sup 6} yr). We suggest that the majority of the Class I sources, including the massive YSOs, are second-generation stars of the region whose formation is possibly induced by the expansion of the H II region powered by a {approx}4 Multiplication-Sign 10{sup 6} yr B0 main-sequence star.« less

46 CFR 56.20-9 - Valve construction.

Code of Federal Regulations, 2010 CFR

2010-10-01

... closed. (b) Valves of Class I piping systems (for restrictions in other classes refer to sections on low temperature service), having diameters exceeding 2 inches must have bolted, pressure seal, or breech lock...

High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends

PubMed Central

Zhang, Pingze; Xie, Guangyao; Liu, Xinxin; Ai, Lili; Chen, Yanyu; Meng, Xin; Bi, Yuhai; Chen, Jianjun; Sun, Yuzhang; Stoeger, Tobias; Ding, Zhuang

2015-01-01

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future. PMID:26712543

High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends.

PubMed

Zhang, Pingze; Xie, Guangyao; Liu, Xinxin; Ai, Lili; Chen, Yanyu; Meng, Xin; Bi, Yuhai; Chen, Jianjun; Sun, Yuzhang; Stoeger, Tobias; Ding, Zhuang; Yin, Renfu

2015-12-28

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules

NASA Technical Reports Server (NTRS)

Chapes, S. K.; Hoynowski, S. M.; Woods, K. M.; Armstrong, J. W.; Beharka, A. A.; Iandolo, J. J.; Spooner, B. S. (Principal Investigator)

1993-01-01

We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.

25 CFR 535.1 - Amendments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... GAMING COMMISSION, DEPARTMENT OF THE INTERIOR MANAGEMENT CONTRACT PROVISIONS POST-APPROVAL PROCEDURES... management contract for the operation of a class II or class III gaming activity. (b) A tribe shall submit an... information required under § 537.1(b)(1) of this chapter for class II gaming contracts or § 537.1(b)(1)(i) of...

40 CFR 144.26 - Inventory requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... “Inventory of Injection Wells,” OMB No. 158-R0170. (b) Additional contents. For EPA administered programs...) Class II enhanced recovery wells; (ii) Class IV wells; (iii) The following Class V wells: (A) Sand or... (40 CFR 146.5 (e)(11)) (C) Geothermal energy recovery wells [§ 146.5(e)(12)]; (D) Brine return flow...

Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses

USDA-ARS?s Scientific Manuscript database

Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by class I and class II, with class II being further divided into eighteen genotypes. Alth...

Effects of Newcastle disease virus vaccine antibodies on the shedding and transmission of challenge viruses

USDA-ARS?s Scientific Manuscript database

Different genotypes of avian paramyxovirus serotype-1 virus (APMV-1) circulate in many parts of the world. Traditionally, Newcastle disease virus (NDV) is recognized as having two major divisions represented by class I and class II, with class II being further divided into sixteen genotypes. Althoug...

41 CFR 301-10.123 - When may I use other than coach-class airline accommodations?

Code of Federal Regulations, 2011 CFR

2011-07-01

... to: (i) Use of coach-class accommodations would endanger your life or Government property; (ii) You... coach-class accommodations would endanger your life or Government property; (ii) You are an agent on... sanitation or health standards; (4) Regularly scheduled flights between origin/destination points (including...

Cognitive Performance in Older Adults with Stable Heart Failure: Longitudinal Evidence for Stability and Improvement

PubMed Central

Alosco, Michael L.; Garcia, Sarah; Spitznagel, Mary Beth; van Dulmen, Manfred; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

2013-01-01

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. PMID:23906182

A Novel HURRAH Protocol Reveals High Numbers of Monomorphic MHC Class II Loci and Two Asymmetric Multi-Locus Haplotypes in the Père David's Deer

PubMed Central

Wan, Qiu-Hong; Zhang, Pei; Ni, Xiao-Wei; Wu, Hai-Long; Chen, Yi-Yan; Kuang, Ye-Ye; Ge, Yun-Fa; Fang, Sheng-Guo

2011-01-01

The Père David's deer is a highly inbred, but recovered, species, making it interesting to consider their adaptive molecular evolution from an immunological perspective. Prior to this study, genomic sequencing was the only method for isolating all functional MHC genes within a certain species. Here, we report a novel protocol for isolating MHC class II loci from a species, and its use to investigate the adaptive evolution of this endangered deer at the level of multi-locus haplotypes. This protocol was designated “HURRAH” based on its various steps and used to estimate the total number of MHC class II loci. We confirmed the validity of this novel protocol in the giant panda and then used it to examine the Père David's deer. Our results revealed that the Père David's deer possesses nine MHC class II loci and therefore has more functional MHC class II loci than the eight genome-sequenced mammals for which full MHC data are currently available. This could potentially account at least in part for the strong survival ability of this species in the face of severe bottlenecking. The results from the HURRAH protocol also revealed that: (1) All of the identified MHC class II loci were monomorphic at their antigen-binding regions, although DRA was dimorphic at its cytoplasmic tail; and (2) these genes constituted two asymmetric functional MHC class II multi-locus haplotypes: DRA1*01 ∼ DRB1 ∼ DRB3 ∼ DQA1 ∼ DQB2 (H1) and DRA1*02 ∼ DRB2 ∼ DRB4 ∼ DQA2 ∼ DQB1 (H2). The latter finding indicates that the current members of the deer species have lost the powerful ancestral MHC class II haplotypes of nine or more loci, and have instead fixed two relatively weak haplotypes containing five genes. As a result, the Père David's deer are currently at risk for increased susceptibility to infectious pathogens. PMID:21267075

Evaluation of the appropriateness and outcome of in-hospital telemetry monitoring.

PubMed

Fålun, Nina; Nordrehaug, Jan Erik; Hoff, Per Ivar; Langørgen, Jørund; Moons, Philip; Norekvål, Tone M

2013-10-15

The American Heart Association classifies monitored patients into 3 categories. The aims of this study were to (1) investigate how patients are assigned according to the American Heart Association classification, (2) determine the number and type of arrhythmic events experienced by these patients, and (3) describe subsequent changes in management. A prospective observational study design was used. All patients assigned to telemetry during a 3-month period were consecutively enrolled in our study. Data were collected 24/7. Only arrhythmias that might require a change in management were recorded. Monitor watchers at the central monitoring station completed a standard data sheet assessing 64 variables. These data, as well as medical records, were reviewed by the investigator. Overall, 1,194 patients were included. Eighteen percent of the patients were assigned to American Heart Association class I (monitoring indicated), 71% to class II (monitoring may be of benefit), and 11% to class III (monitoring not indicated). The overall arrhythmia event rate was 33%. Forty-three percent of class I patients, 28% of class II patients, and 47% of class III patients experienced arrhythmia events. Change in management occurred in 25% of class I patients, 14% of class II patients, and 29% of class III patients. Although the number of class III indications should have been reduced, nearly 1/2 of class III patients experienced arrhythmia events and 1/3 of them received management changes. This outcome challenges existing guidelines. In conclusion, most patients in this study were monitored appropriately, according to class I and II indications. Copyright © 2013 Elsevier Inc. All rights reserved.

Asymmetric severe skeletal Class II division 1 patient with temporomandibular joint disorder treated with zygomatic anchorage devices and Ni-Ti alloy wires.

PubMed

Ishida, Takayoshi; Ono, Takashi

2014-09-01

To describe the orthodontic treatment of a nongrowing 30-year-old woman with asymmetric severe skeletal Class II malocclusions (asymmetric Angle Class II), large overjet (16 mm), large overbite (8 mm), two congenitally missing mandibular incisors (presenting a deciduous anterior tooth), and signs and symptoms of temporomandibular joint disorder (TMD). We used novel improved super-elastic Ni-Ti alloy wires (ISWs) combined with Ni-Ti alloy coil springs, power hooks, and a zygomatic implant as reinforced anchorage to provide a constant and continuous mild force to the dentition. We successfully distalized maxillary molars, premolars, and retracted anterior teeth and corrected the asymmetric Angle Class II molar relationship using this system of zygomatic anchorage in conjunction with ISWs, Ni-Ti alloy open-coil springs, and crimpable power hook. The maxillary molars were distalized, and postero-occlusal relationships were improved to achieve Class I canine and molar relationships on both sides. Intrusion of the upper molars made the mandibular plane close. Ideal overbite and overjet relationships were established. Facial esthetics were improved with decreased upper and lower lip protrusion, and no symptoms of TMD were observed after treatment. The orthodontic treatment described here is a promising anchorage technique alternative to traditional techniques to improve severe skeletal Class II with TMD.

Long-term effects of Class II orthodontic treatment on oral health.

PubMed

Bock, N C; Saffar, M; Hudel, H; Evälahti, M; Heikinheimo, K; Rice, D P C; Ruf, S

2018-03-01

To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

Di-codon Usage for Gene Classification

NASA Astrophysics Data System (ADS)

Nguyen, Minh N.; Ma, Jianmin; Fogel, Gary B.; Rajapakse, Jagath C.

Classification of genes into biologically related groups facilitates inference of their functions. Codon usage bias has been described previously as a potential feature for gene classification. In this paper, we demonstrate that di-codon usage can further improve classification of genes. By using both codon and di-codon features, we achieve near perfect accuracies for the classification of HLA molecules into major classes and sub-classes. The method is illustrated on 1,841 HLA sequences which are classified into two major classes, HLA-I and HLA-II. Major classes are further classified into sub-groups. A binary SVM using di-codon usage patterns achieved 99.95% accuracy in the classification of HLA genes into major HLA classes; and multi-class SVM achieved accuracy rates of 99.82% and 99.03% for sub-class classification of HLA-I and HLA-II genes, respectively. Furthermore, by combining codon and di-codon usages, the prediction accuracies reached 100%, 99.82%, and 99.84% for HLA major class classification, and for sub-class classification of HLA-I and HLA-II genes, respectively.

World War II: A Technology Lesson Plan.

ERIC Educational Resources Information Center

Hagar, Suzy

1990-01-01

Presents a class activity on the history, causes, and consequences of World War II. Focuses on the development and deployment of the atomic bomb. Utilizes a Video Encyclopedia Program for historical background. Divides the class into groups that are responsible for researching and preparing a videotape on a World War II topic. (RW)

75 FR 36134 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... categories of market participants: (i) Market Maker; (ii) Market Maker Plus; \\4\\ (iii) Non-ISE Market Maker... removing liquidity to the following class of market participants: (i) Customer, (ii) Directed Participant... provides a rebate for adding liquidity to the following class of market participants: (i) Customer, (ii...

Kidney graft recipients with pretransplantation HLA CLASS I antibodies and high soluble CD30 are at high risk for graft loss.

PubMed

Rodríguez, Libia M; París, Sara C; Arbeláez, Mario; Cotes, José M; Süsal, Caner; Torres, Yolanda; García, Luís F

2007-08-01

In the present study, we investigated whether pretransplantation HLA class I and class II antibodies and pretransplantation levels of soluble CD30 (sCD30) and IgA anti-Fab autoantibodies are predictive of kidney allograft survival. Pretransplantation sera of 504 deceased-donor kidney recipients were tested for IgG HLA class I and class II antibodies, sCD30, and IgA anti-Fab levels using the CTS 4 ELISA kit. Kidney graft survival was estimated by Kaplan-Meier method and multivariate Cox regression. Regardless of the presence of HLA class II antibodies, recipients with high HLA class I reactivity had lower 1-year graft survival than recipients with low reactivity (p < 0.01). Recipients with high sCD30 had lower 5-year graft survival rate than those with low sCD30 (p < 0.01). The sCD30 effect was observed in presensitized and nonsensitized recipients, demonstrated a synergistic effect with HLA class I antibodies (p < 0.001), and appeared to be neutralized in recipients with no HLA class II mismatches. IgA anti-Fab did not influence kidney graft survival. Our results indicate that high pretransplantation sCD30 levels and HLA class I positivity increase the risk of kidney graft loss regardless of other factors. Consequently, such determinations should be routinely performed to estimate recipients' risks of graft rejection before transplantation.

44 CFR 402.4 - Calls at restricted ports en route to an unrestricted port with restricted cargo.

Code of Federal Regulations, 2012 CFR

2012-10-01

... port or other place in Communist China.) For example, an American flag ship may call at one of the restricted ports (except one in Communist China), even though it has on board the following classes of... for Communist China (the transportation and discharge of which is covered by Order T-2). None of these...

44 CFR 402.4 - Calls at restricted ports en route to an unrestricted port with restricted cargo.

Code of Federal Regulations, 2013 CFR

2013-10-01

... port or other place in Communist China.) For example, an American flag ship may call at one of the restricted ports (except one in Communist China), even though it has on board the following classes of... for Communist China (the transportation and discharge of which is covered by Order T-2). None of these...

44 CFR 402.4 - Calls at restricted ports en route to an unrestricted port with restricted cargo.

Code of Federal Regulations, 2014 CFR

2014-10-01

... port or other place in Communist China.) For example, an American flag ship may call at one of the restricted ports (except one in Communist China), even though it has on board the following classes of... for Communist China (the transportation and discharge of which is covered by Order T-2). None of these...

44 CFR 402.4 - Calls at restricted ports en route to an unrestricted port with restricted cargo.

Code of Federal Regulations, 2010 CFR

2010-10-01

... port or other place in Communist China.) For example, an American flag ship may call at one of the restricted ports (except one in Communist China), even though it has on board the following classes of... for Communist China (the transportation and discharge of which is covered by Order T-2). None of these...

44 CFR 402.4 - Calls at restricted ports en route to an unrestricted port with restricted cargo.

Code of Federal Regulations, 2011 CFR

2011-10-01

... port or other place in Communist China.) For example, an American flag ship may call at one of the restricted ports (except one in Communist China), even though it has on board the following classes of... for Communist China (the transportation and discharge of which is covered by Order T-2). None of these...

Characterization of swine leucocyte antigen alleles in a crossbred pig to be used in xenotransplant studies.

PubMed

Reyes, L M; Blosser, R J; Smith, R F; Miner, A C; Paris, L L; Blankenship, R L; Tector, M F; Tector, A J

2014-11-01

We have characterized swine leucocyte antigen (SLA) classes I and II molecules of a domestic pig as a model for use in our xenotransplant program. Molecular characterization of the SLA classes I and II genes is critical to understanding the adaptive immune responses between swine and humans in the event of xenotransplantation. Seven swine leucocyte antigen genes (SLA-1, SLA-2, SLA-3, DQB1, DRB1, DQA and DRA) were analyzed and 15 alleles were identified. A novel DRA*w04re01 is reported for this limited polymorphic class II gene. The heterozygous haplotypes, Hp-32.0/35.0 and Hp-0.13/0.23 were deduced for our IU-pig model, for SLA classes I and II regions, respectively. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification, characterization, and quantitation of soluble HLA antigens in the circulation and peritoneal dialysate of renal patients.

PubMed Central

Gelder, F B; McDonald, J C; Landreneau, M D; McMillan, R M; Aultman, D F

1991-01-01

Human lymphocyte antigen (HLA) class I and class II antigens and beta 2 microglobulin (B2M) were identified in peritoneal dialysate (PD) and serum from patients with end-stage renal disease (ESRD) using monoclonal antibodies in an enzyme-linked immunoassay. The HLA class I and class II antigens each exhibited approximate molecular weights of 50,000 to 60,000 daltons by chromatography on Sepharose CL 6B. Class I antigens in serum and PD fluid were associated with B2M. Free B2M (Mr 11,500) also was detected in both sera and PD fluids. Unlike class I antigens, class II antigens were not found to have attached B2M. Class I and class II antigens eluted from 2-diethylaminoethanol ion exchange gradient columns at 0.07 mol/L (molar) phosphate buffer pH 7.2 and migrated with alpha 2-beta 1 mobility in agarose electrophoresis. Class I antigens were purified from ESRD patients' PD fluid by solid-phase immunoaffinity chromatography. Enzyme-linked immunoassay demonstrated that this purified protein was composed of a class I heavy chain and B2M. Class I allospecificity was confirmed by neutralization on known HLA typing antisera in a microcytotoxicity assay. Soluble HLA class I antigen preparations specifically inhibited blast transformation of responder lymphocytes in mixed lymphocyte culture reactions. Inhibition was dose dependent and ranged from 0% to 95%. The presence of soluble HLA antigens in body fluids may play an important part in the immunologic tolerance to self. This study demonstrates a ready source of large quantities of soluble HLA for detailed analysis. Images Fig. 1. PMID:2039290

Analysis of Class II patients, successfully treated with the straight-wire and Forsus appliances, based on cervical vertebral maturation status.

PubMed

Servello, David F; Fallis, Drew W; Alvetro, Lisa

2015-01-01

To assess skeletal and dental changes in patients successfully treated with the Forsus appliance based on cervical vertebral maturation status. Forty-seven Class II patients, successfully treated with the Forsus appliance, were divided into peak and postpeak growth groups determined immediately prior to Forsus placement. The mean (SD) ages of the peak and postpeak groups were 13.4 (1.0) and 14.1 (1.3) years, respectively. Superimpositions of initial, Forsus placement, Forsus removal, and final cephalometric radiographs were completed, allowing the measurement of changes during three treatment phases. There were no significant differences between groups during treatment phase 1 (alignment/leveling), with both groups demonstrating a worsening of the Class II molar relationship. However, during treatment phase 2 (Class II correction), patients within the peak group demonstrated significantly higher mean apical base, mandibular and molar changes, and an increased rate of change compared with those in the postpeak group. No significant differences were observed during treatment phase 3 (detail/finishing). Following an initial worsening of the Class II molar relationship as a result of straight-wire appliance effects, Forsus appliance treatment initiated during cervical vertebral maturation status (CS) 3-4 elicits more effective and efficient correction of Class II molar relationships than when initiated during CS 5-6. Data support that these effects are due mainly to maxillary skeletal and dentoalveolar restraint during a period of more rapid mandibular growth.

Nonsurgical treatment of an adult with a skeletal Class II gummy smile using zygomatic temporary anchorage devices and improved superelastic nickel-titanium alloy wires.

PubMed

Ishida, Yuji; Ono, Takashi

2017-11-01

Patients with a severe gummy smile and a skeletal Class II profile are difficult to treat. This case report describes an effective treatment alternative for improving a gummy smile in a patient with a severe Class II molar relationship, severe crowding, and lip protrusion using zygomatic anchorage devices and improved superelastic nickel-titanium wires. A 36-year-old woman had an excessive overjet and a deep overbite with a bilateral Angle Class II molar relationship. The cephalometric analysis demonstrated a Class II skeletal relationship (ANB, 9.5°), retroclination of the mandible (FMA, 38.4°), and severe labial inclination of the mandibular incisors (IMPA, 101.9°). The main treatment objectives included normalizing the overjet and overbite, improving the gummy smile, and establishing a satisfactory occlusion. During treatment with fixed appliances, intrusion of the total maxillary dentition using skeletal anchorage and elimination of the bimaxillary protrusion were achieved. Improvement of the lateral profile and gummy smile enhanced facial esthetics. Intrusion and distalization of the maxillary dentition with skeletal anchorage and improved superelastic nickel-titanium wires provided a satisfactory dental occlusion, esthetic improvement, and adequate function. This approach should be considered as an alternative treatment option to orthognathic surgery for adults with high-angle skeletal Class II malocclusion and a gummy smile. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Probing the Evolution of Massive Young Stellar Objects using Weak Class II 6.7GHz Methanol Maser Emission

NASA Astrophysics Data System (ADS)

Ludwig, Bethany Ann; Cunningham, Nichol

2017-01-01

We present results from an investigation of class II 6.7GHz methanol masers towards four Massive Young Stellar Objects (MYSOs). The sources, selected from the Red MSX Source (RMS) Survey (Lumsden et al. 2013), were previously understood to be non-detections for class II methanol maser emission in the methanol multi-beam (MMB) Survey (Caswell et al. 2010.) Class II methanol masers are a well-known sign post of massive star forming regions and may be utilized to probe their relatively poorly understood formation. It is possible that these non-detections are simply weak masers that are potentially associated with a younger evolutionary phase of MYSOs as hypothesized by Olmi et al. (2014). The sources were chosen to sample various stages of evolution, having similar 21 to 8 micron flux ratios and bolometric luminosities as other MYSOs with previous class II methanol maser detections. We observed all 4 MYSOs with ATCA (~2" resolution) at 10 times deeper sensitivity than previously obtained with the MMB survey and have a spectral resolution of 0.087kms^-1 . The raw data is reduced using the program Miriad (Sault, R. J., et al., 1995) and deconvolutioned using the program CASA (McMullin, J. P., et al. 2007.) We determine one of the four observed MYSOs is harboring a weak class II methanol maser. We discuss the possibility of sensitivity limitations on the remaining sources as well as environmental and evolutionary differences between the sources.

The activation threshold of CD4+ T cells is defined by TCR/peptide-MHC class II interactions in the thymic medulla.

PubMed

Stephen, Tom Li; Tikhonova, Anastasia; Riberdy, Janice M; Laufer, Terri M

2009-11-01

Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells that are not overtly reactive to those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive thymocytes are attenuated to respond appropriately to the peptide-MHC molecules that will be encountered in the periphery. In this study, we explore the mechanisms that regulate the tuning of CD4(+) single-positive T cells to MHC class II encountered in the thymic medulla. Experiments with murine BM chimeras demonstrate that tuning can be mediated by MHC class II expressed by either thymic medullary epithelial cells or thymic dendritic cells. Tuning does not require the engagement of CD4 by MHC class II on stromal cells. Rather, it is mediated by interactions between MHC class II and the TCR. To understand the molecular changes that distinguish immature hyperactive T cells from tuned mature CD4(+) T cells, we compared their responses to TCR stimulation. The altered response of mature CD4 single-positive thymocytes is characterized by the inhibition of ERK activation by low-affinity self-ligands and increased expression of the inhibitory tyrosine phosphatase SHP-1. Thus, persistent TCR engagement by peptide-MHC class II on thymic medullary stroma inhibits reactivity to self-Ags and prevents autoreactivity in the mature repertoire.

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.

PubMed

Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi

2007-03-15

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.

The Influence of Class II Division 2 Malocclusions on the Harmony of the Human Face Profile.

PubMed

Perović, Tatjana

2017-11-24

BACKGROUND Persons with class II division 2 malocclusion are characterized by a very specific dento-skeletal and soft-tissue profile (a profile in which a protruding nose and chin, retruding lips, concave and shortened lower third of the face, and gummy smile are dominant), which is the opposite of the currently modern profiles (convex profile of protruding lips and small chin). The aim of this research was to determine the differences in parameters of harmonies of facial profiles between persons with class II division 2 malocclusions and class I, and to establish the significance of those differences. MATERIAL AND METHODS For this study, 50 patients with class II division 2 malocclusions and 50 patients with class I were selected; profile photos were recorded and a photometric analysis was done: a type of profile according to Schwarz, the shape of a nose, the prominence of chin, biometrical field, the position of lips in relation to the tangent Sn-Pg, S-line (Steiner), E-line (Riketts) and a facial angle according to Arnett. RESULTS The significant differences in profiles of persons with class II division 2 compared to class I were: position and prominence of the chin, the position of the lower and upper lip in relation to the S-line, and smaller value of a facial angle in relation to persons with class I. CONCLUSIONS The differences seen in skeletal profiles were not associated with significant differences in the profiled facial contours of the examined groups. The compensatory role of the fullness of soft tissues of the lips is probably the reason why there were not significant deviations in all the examined parameters.

Nuclear congression and membrane fusion: two distinct events in the yeast karyogamy pathway

PubMed Central

1994-01-01

Karyogamy is the process where haploid nuclei fuse to form a diploid nucleus during yeast mating. We devised a novel genetic screen that identified five new karyogamy (KAR) genes and three new cell fusion (FUS) genes. The kar mutants fell into two classes that represent distinct events in the yeast karyogamy pathway. Class I mutations blocked congression of the nuclei due to cytoplasmic microtubule defects. In Class II mutants, nuclear congression proceeded and the membranes of apposed nuclei were closely aligned but unfused. In vitro, Class II mutant membranes were defective in a homotypic ER/nuclear membrane fusion assay. We propose that Class II mutants define components of a novel membrane fusion complex which functions during vegetative growth and is recruited for karyogamy. PMID:8051211

Object class segmentation of RGB-D video using recurrent convolutional neural networks.

PubMed

Pavel, Mircea Serban; Schulz, Hannes; Behnke, Sven

2017-04-01

Object class segmentation is a computer vision task which requires labeling each pixel of an image with the class of the object it belongs to. Deep convolutional neural networks (DNN) are able to learn and take advantage of local spatial correlations required for this task. They are, however, restricted by their small, fixed-sized filters, which limits their ability to learn long-range dependencies. Recurrent Neural Networks (RNN), on the other hand, do not suffer from this restriction. Their iterative interpretation allows them to model long-range dependencies by propagating activity. This property is especially useful when labeling video sequences, where both spatial and temporal long-range dependencies occur. In this work, a novel RNN architecture for object class segmentation is presented. We investigate several ways to train such a network. We evaluate our models on the challenging NYU Depth v2 dataset for object class segmentation and obtain competitive results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of psychosocial status in treatment-seeking women with class III vs. class I-II obesity.

PubMed

Wadden, Thomas A; Butryn, Meghan L; Sarwer, David B; Fabricatore, Anthony N; Crerand, Canice E; Lipschutz, Patti E; Faulconbridge, Lucy; Raper, Steven; Williams, Noel N

2006-01-01

This study compared the psychosocial status and weight loss expectations of women with extreme (class III) obesity who sought bariatric surgery with those of women with class I-II obesity who enrolled in a research study on behavioral weight control. Before treatment, all participants completed the Beck Depression Inventory-II and the Weight and Lifestyle Inventory. This latter questionnaire assesses several domains including symptoms of depression and low self-esteem, history of psychiatric complications, current stressors, and weight loss expectations. Women with class III obesity, as compared with class I-II, reported significantly more symptoms of depression. Fully 25% of women in the former group appeared to have a significant mood disorder that would benefit from treatment. As compared with women with class I-II obesity, significantly more women with class III obesity also reported a history of psychiatric complications, which included physical and sexual abuse and greater stress related to their physical health and financial/legal matters. Both groups of women had unrealistic weight loss expectations. Those who sought surgery expected to lose 47.6 +/- 9.3% of initial weight, compared with 24.8 +/- 8.7% for those who enrolled in behavioral weight control. These findings suggest that women with extreme obesity who seek bariatric surgery should be screened for psychosocial complications. Those determined to have significant psychiatric distress should be referred for behavioral or pharmacological treatment to alleviate their suffering. Long-term studies are needed to provide definitive guidance concerning the relationship between preoperative psychopathology and the outcome of bariatric surgery.

33 CFR 334.1210 - Admiralty Inlet, entrance; naval restricted area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Admiralty Inlet, entrance; naval..., entrance; naval restricted area. (a) Admiralty Inlet, entrance; naval restricted area—(1) The area... prohibited. (ii) The regulations in this paragraph shall be enforced by the Commander, Naval Base, Seattle...

33 CFR 334.1210 - Admiralty Inlet, entrance; naval restricted area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Admiralty Inlet, entrance; naval..., entrance; naval restricted area. (a) Admiralty Inlet, entrance; naval restricted area—(1) The area... prohibited. (ii) The regulations in this paragraph shall be enforced by the Commander, Naval Base, Seattle...

On the Effects of Social Class on Language Use: A Fresh Look at Bernstein's Theory

ERIC Educational Resources Information Center

Aliakbari, Mohammad; Allahmoradi, Nazal

2014-01-01

Basil Bernstein (1971) introduced the notion of the Restricted and the Elaborated code, claiming that working-class speakers have access only to the former but middle-class members to both. In an attempt to test this theory in the Iranian context and to investigate the effect of social class on the quality of students language use, we examined the…

An update on alopecia areata.

PubMed

Kos, Liborka; Conlon, Joseph

2009-08-01

Alopecia areata is one of the most frequent organ-restricted autoimmune diseases, yet its pathogenesis is still unclear. In addition, although alopecia areata often results in significant psychological distress, effective treatment is lacking. New potential susceptibility loci have been implicated, but the strongest evidence points to certain class II human leukocyte antigen alleles. There is new evidence for the collapse of hair follicle immune privilege as a key step in the pathogenesis of alopecia areata. There is also new basic science evidence for stress as a contributing factor in the development of alopecia areata. Few treatments for alopecia areata have been well evaluated in randomized trials. Although multiple potential susceptibility loci have been implicated, the genetics of alopecia areata is still unclear. The role of any potential environmental contributors is also unclear. Quality evidence for efficacy of currently used treatments for alopecia areata is lacking.

Method of artificial DNA splicing by directed ligation (SDL).

PubMed Central

Lebedenko, E N; Birikh, K R; Plutalov, O V; Berlin YuA

1991-01-01

An approach to directed genetic recombination in vitro has been devised, which allows for joining together, in a predetermined way, a series of DNA segments to give a precisely spliced polynucleotide sequence (DNA splicing by directed ligation, SDL). The approach makes use of amplification, by means of several polymerase chain reactions (PCR), of a chosen set of DNA segments. Primers for the amplifications contain recognition sites of the class IIS restriction endonucleases, which transform blunt ends of the amplification products into protruding ends of unique primary structures, the ends to be used for joining segments together being mutually complementary. Ligation of the mixture of the segments so synthesized gives the desired sequence in an unambiguous way. The suggested approach has been exemplified by the synthesis of a totally processed (intronless) gene encoding human mature interleukin-1 alpha. Images PMID:1662363

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

40 CFR 147.2650 - State-administered program-Class I, II, III, IV, and V wells.

Code of Federal Regulations, 2013 CFR

2013-07-01

... CONTROL PROGRAMS Puerto Rico § 147.2650 State-administered program—Class I, II, III, IV, and V wells. The Underground Injection Control Program for all classes of wells in the Commonwealth of Puerto Rico, other than those on Indian lands, is the program administered by Puerto Rico's Environmental Quality Board (EQB...

Reliability of Growth Indicators and Efficiency of Functional Treatment for Skeletal Class II Malocclusion: Current Evidence and Controversies.

PubMed

Perinetti, Giuseppe; Contardo, Luca

2017-01-01

Current evidence on the reliability of growth indicators in the identification of the pubertal growth spurt and efficiency of functional treatment for skeletal Class II malocclusion, the timing of which relies on such indicators, is highly controversial. Regarding growth indicators, the hand and wrist (including the sole middle phalanx of the third finger) maturation method and the standing height recording appear to be most reliable. Other methods are subjected to controversies or were showed to be unreliable. Main sources of controversies include use of single stages instead of ossification events and diagnostic reliability conjecturally based on correlation analyses. Regarding evidence on the efficiency of functional treatment, when treated during the pubertal growth spurt, more favorable response is seen in skeletal Class II patients even though large individual responsiveness remains. Main sources of controversies include design of clinical trials, definition of Class II malocclusion, and lack of inclusion of skeletal maturity among the prognostic factors. While no growth indicator may be considered to have a full diagnostic reliability in the identification of the pubertal growth spurt, their use may still be recommended for increasing efficiency of functional treatment for skeletal Class II malocclusion.

Treatment of class ii in adulthood by forsus frd device.

PubMed

DE Nuccio, F; D'Emidio, M M; DE Nuccio, F

2016-01-01

Scientific research data show that the Forsus FRD seems to have a great potential in the correction of Class II in childhood. The conclusions reached by the various Authors seem to support the hypothesis of an exclusively or mainly dentoalveolar correction, as the skeletal correction seems to have no - or little - appreciable results. In the light of such provided by different Authors, the potential of dentoalveolar compensation in adult patients with mild skeletal class II was investigated. At the UOC (Complex Operative Unit) of Orthodontics at "G. Eastman" Hospital Rome, 3 cases of skeletal class II mild (ANB <5 °) in adult patients were selected. They were treated with fixed multibracket appliance and Forsus EZ2 module. Cephalometric tracings were compared at the beginning and at the end of the treatment in order to assess the skeletal and dentoalveolar changes. The occlusal correction was achieved through a dentoalveolar compensation characterized by the flaring of the lower teeth. Forsus FRD equipment is an excellent compromise for the correction of mild Class II, even during the post development age. The resulting correction is appreciated at dental alveolar level with a mesial movement of the incisors and molars.

Reliability of Growth Indicators and Efficiency of Functional Treatment for Skeletal Class II Malocclusion: Current Evidence and Controversies

PubMed Central

2017-01-01

Current evidence on the reliability of growth indicators in the identification of the pubertal growth spurt and efficiency of functional treatment for skeletal Class II malocclusion, the timing of which relies on such indicators, is highly controversial. Regarding growth indicators, the hand and wrist (including the sole middle phalanx of the third finger) maturation method and the standing height recording appear to be most reliable. Other methods are subjected to controversies or were showed to be unreliable. Main sources of controversies include use of single stages instead of ossification events and diagnostic reliability conjecturally based on correlation analyses. Regarding evidence on the efficiency of functional treatment, when treated during the pubertal growth spurt, more favorable response is seen in skeletal Class II patients even though large individual responsiveness remains. Main sources of controversies include design of clinical trials, definition of Class II malocclusion, and lack of inclusion of skeletal maturity among the prognostic factors. While no growth indicator may be considered to have a full diagnostic reliability in the identification of the pubertal growth spurt, their use may still be recommended for increasing efficiency of functional treatment for skeletal Class II malocclusion. PMID:28168195

46 CFR 128.210 - Class II vital systems-materials.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Materials and Pressure Design § 128.210 Class II vital systems—materials... Commanding Officer, Marine Safety Center, if shown to provide a level of safety equivalent to materials in...

46 CFR 128.210 - Class II vital systems-materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Materials and Pressure Design § 128.210 Class II vital systems—materials... Commanding Officer, Marine Safety Center, if shown to provide a level of safety equivalent to materials in...

46 CFR 128.210 - Class II vital systems-materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Materials and Pressure Design § 128.210 Class II vital systems—materials... Commanding Officer, Marine Safety Center, if shown to provide a level of safety equivalent to materials in...

46 CFR 128.210 - Class II vital systems-materials.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Materials and Pressure Design § 128.210 Class II vital systems—materials... Commanding Officer, Marine Safety Center, if shown to provide a level of safety equivalent to materials in...

46 CFR 128.210 - Class II vital systems-materials.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Materials and Pressure Design § 128.210 Class II vital systems—materials... Commanding Officer, Marine Safety Center, if shown to provide a level of safety equivalent to materials in...

HLA antibodies and soluble CD30 are associated with poor renal graft outcome: updated results of a single-center cross-sectional study.

PubMed

Langan, Leanne L; D'Orsogna, Lloyd; Park, Lawrence P; Hughes, Tiffany L; Irish, Ashley; Luxton, Grant; Witt, Campbell S; Christiansen, Frank T

2006-01-01

In a previous study, we have shown that HLA class II antibodies and a high soluble CD30 (sCD30) measured at least 1 year post-transplant predict subsequent graft failure. We have now updated the results of this same cohort of 208 patients 15 months later. HLA-specific antibodies (class I and class II) were detected by ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up of 4.7 years. By Kaplan-Meier analysis, class II antibody was again associated with a poorer outcome, with an estimated 6-year graft survival of 67% and 71% when detected by ELISA and Luminex, respectively, compared with 92% for those without class II antibody (p < or = 0.0001). A soluble CD30 level of > or = 100 U/ml was also associated with a poorer estimated 6-year graft survival (p = 0.02). HLA antibodies and high sCD30 (> or = 100 U/ml) had an additive effect such that those with both high sCD30 and class II antibodies had a hazard ratio for subsequent graft failure of 18.1 (p = 0.0008) and 8.6 (p = 0.007) when detected by ELISA and Luminex, respectively. These data show that detection of HLA class II antibodies and serum sCD30 measured at least 1 year post-transplant continues to predict a subsequent outcome up to 6 years after the initial measurement; they also show that such measures provide important information that may allow for modification of ongoing therapy.

Relationship between crown-root angulation (collum angle) of maxillary central incisors in Class II, division 2 malocclusion and lower lip line.

PubMed

Srinivasan, Bhadrinath; Kailasam, Vignesh; Chitharanjan, Arun; Ramalingam, Arthi

2013-01-01

The present study aimed to measure the magnitude of the collum angle (crown-root angulation) of maxillary central incisors present in Class II, division 2 malocclusion and to relate the changes in its magnitude with variations in the lower lip line. A set of 120 conventional lateral cephalograms were selected and divided into three groups of 40 each based on the type of malocclusion presented: Class II, division 2 (group 1); Class II, division 1 (group 2); and Class I (group 3). The collum angle of the maxillary central incisor was measured, and the lower lip line was recorded. Analysis of variance (ANOVA) revealed that the mean collum angle was statistically significantly different in the three groups. The mean collum angle was greatest in Class II, division 2 malocclusion (group 1). The mean collum angles were 3.24 ± 4.69 degrees, 0.95 ± 1.06 degrees, and 1.05 ± 1.50 degrees in groups 1, 2, and 3 respectively. In χ ² test comparison of the location of the lower lip line (incisal, middle, or apical third of the central incisor) among the three groups, the lower lip line was found to contact the middle third of the central incisor most frequently in Class II, division 2 malocclusion. ANOVA followed by Tukey honestly significant difference (HSD) test showed that the mean collum angle is significantly increased when the lower lip is in the middle third (P < .05) of the central incisor. Variations in magnitude of the collum angle with the change in the lower lip line suggest a probable etiologic role of the lower lip line in the development of the collum angle.

Molecular Characterization, Gene Evolution, and Expression Analysis of the Fructose-1, 6-bisphosphate Aldolase (FBA) Gene Family in Wheat (Triticum aestivum L.)

PubMed Central

Lv, Geng-Yin; Guo, Xiao-Guang; Xie, Li-Ping; Xie, Chang-Gen; Zhang, Xiao-Hong; Yang, Yuan; Xiao, Lei; Tang, Yu-Ying; Pan, Xing-Lai; Guo, Ai-Guang; Xu, Hong

2017-01-01

Fructose-1, 6-bisphosphate aldolase (FBA) is a key plant enzyme that is involved in glycolysis, gluconeogenesis, and the Calvin cycle. It plays significant roles in biotic and abiotic stress responses, as well as in regulating growth and development processes. In the present paper, 21 genes encoding TaFBA isoenzymes were identified, characterized, and categorized into three groups: class I chloroplast/plastid FBA (CpFBA), class I cytosol FBA (cFBA), and class II chloroplast/plastid FBA. By using a prediction online database and genomic PCR analysis of Chinese Spring nulli-tetrasomic lines, we have confirmed the chromosomal location of these genes in 12 chromosomes of four homologous groups. Sequence and genomic structure analysis revealed the high identity of the allelic TaFBA genes and the origin of different TaFBA genes. Numerous putative environment stimulus-responsive cis-elements have been identified in 1,500-bp regions of TaFBA gene promoters, of which the most abundant are the light-regulated elements (LREs). Phylogenetic reconstruction using the deduced protein sequence of 245 FBA genes indicated an independent evolutionary pathway for the class I and class II groups. Although, earlier studies have indicated that class II FBA only occurs in prokaryote and fungi, our results have demonstrated that a few class II CpFBAs exist in wheat and other closely related species. Class I TaFBA was predicted to be tetramers and class II to be dimers. Gene expression analysis based on microarray and transcriptome databases suggested the distinct role of TaFBAs in different tissues and developmental stages. The TaFBA 4–9 genes were highly expressed in leaves and might play important roles in wheat development. The differential expression patterns of the TaFBA genes in light/dark and a few abiotic stress conditions were also analyzed. The results suggested that LRE cis-elements of TaFBA gene promoters were not directly related to light responses. Most TaFBA genes had higher expression levels in the roots than in the shoots when under various stresses. Class I cytosol TaFBA genes, particularly TaFBA10/12/18 and TaFBA13/16, and three class II TaFBA genes are involved in responses to various abiotic stresses. Class I CpFBA genes in wheat are apparently sensitive to different stress conditions. PMID:28659962

Tooth size discrepancies in Class II division 1 and Class III malocclusion requiring surgical-orthodontic or orthodontic treatment.

PubMed

McSwiney, Timothy P; Millett, Declan T; McIntyre, Grant T; Barry, Mark K; Cronin, Michael S

2014-06-01

To compare mean anterior (AR) and mean overall (OR) tooth size ratios, prevalence of clinically significant tooth size discrepancies (TSDs) and correlation between AR and OR in subjects with Class II division 1 and Class III malocclusion treated by surgical-orthodontic or orthodontic means. Retrospective, cross-sectional. State-funded and private clinics. From pre-treatment cohorts of 770 surgical and 610 non-surgical subjects, Class II division 1 and Class III malocclusion groups were identified with 60 surgical and 60 non-surgical subjects, comprising 30 males and 30 females, in each. AR and OR were calculated by landmarking digital models. Differences in AR and OR and their relationship were analysed using two-way analysis of variance (ANOVA) and a correlation coefficient, respectively. The proportions of the surgical and non-surgical groups with a TSD were assessed using logistic regression. Intra-examiner reproducibility involved re-landmarking 30 randomly selected image sets and differences in ARs and ORs were compared using a paired t-test. Random error was assessed using the intraclass correlation coefficient (ICC). Analyses were performed using SAS (SAS Institute Inc., Cary, NC, USA) at the 5% level of significance. There were no statistically significant differences associated with the measurement of either the mean AR (P = 0·913) or the mean OR (P = 0·874). ICC values were very high (AR = 0·95; OR = 0·90). Differences existed between both Class II and Class III surgical (AR: P<0·001; OR: P<0·001) and non-surgical groups (AR: P = 0·012; OR: P = 0·003). The AR and OR relationship was strong (correlation coefficient = 0·72). The highest percentage of clinically significant TSDs was seen in the AR of both Class II and Class III surgical groups (23·3%). In the cohort examined: AR and OR differed significantly for malocclusion groups. The prevalence of clinically significant TSDs did not differ significantly between surgical and non-surgical groups although the highest percentage of clinically significant TSDs was recorded for AR in Class II and Class III surgical cases. AR and OR were closely related. © 2014 British Orthodontic Society.

Mouse HLA-DPA homologue H2-Pa: A pseudogene that maps between H2-Pb and H2-Oa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arimura, Y.; Koda, T.; Kishi, M.

1996-12-31

The major histocompatibility complex (MHC) class II subregion contains several subclasses of genes. The classical class II genes, HLA-DP, DQ, and DR homologues, present antigens directly to CD4{sup +} T cells. HLA-DM homologues facilitate the efficacy and transport of antigens to the cell surface by removing the CLIP peptides from the classical class II molecules. HLA-DNA/DOB homologues show unusual expression patterns and limited polymorphism, but their function is yet to be elucidated. 15 refs., 2 figs.

Vendor compliance with Ontario's tobacco point of sale legislation.

PubMed

Dubray, Jolene M; Schwartz, Robert M; Garcia, John M; Bondy, Susan J; Victor, J Charles

2009-01-01

On May 31, 2006, Ontario joined a small group of international jurisdictions to implement legislative restrictions on tobacco point of sale promotions. This study compares the presence of point of sale promotions in the retail tobacco environment from three surveys: one prior to and two following implementation of the legislation. Approximately 1,575 tobacco vendors were randomly selected for each survey. Each regionally-stratified sample included equal numbers of tobacco vendors categorized into four trade classes: chain convenience, independent convenience and discount, gas stations, and grocery. Data regarding the six restricted point of sale promotions were collected using standardized protocols and inspection forms. Weighted estimates and 95% confidence intervals were produced at the provincial, regional and vendor trade class level using the bootstrap method for estimating variance. At baseline, the proportion of tobacco vendors who did not engage in each of the six restricted point of sale promotions ranged from 41% to 88%. Within four months following implementation of the legislation, compliance with each of the six restricted point of sale promotions exceeded 95%. Similar levels of compliance were observed one year later. Grocery stores had the fewest point of sale promotions displayed at baseline. Compliance rates did not differ across vendor trade classes at either follow-up survey. Point of sale promotions did not differ across regions in any of the three surveys. Within a short period of time, a high level of compliance with six restricted point of sale promotions was achieved.

MRP (materiel requirements planning) II implementation: a case study.

PubMed

Sheldon, D

1994-05-01

Manufacturing resource planning (MRP II) is a powerful and effective business planning template on which to build a continuous improvement culture. MRP II, when successfully implemented, encourages a disciplined yet nonthreatening environment centered on measurement and accountability. From the education that accompanies an MRP II implementation, the employees can better understand the vision and mission of the organization. This common goal keeps everyone's energy directed toward the same final objective. The Raymond Corporation is a major materiels handling equipment manufacturer headquartered in Greene, New York, with class "A" MRP II manufacturing facilities in Greene and Brantford, Ontario and an aftermark distribution facility in East Syracuse, New York. Prior to the implementation of MRP II in its Greene plant (from 1988 through 1990) good intentions and hard work were proving to be less than necessary to compete in the global market. Certified class "A" in February 1990. The Raymond Corporation has built a world-class organization from these foundations.

Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

PubMed

Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

2005-09-01

In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination.

Sequential cloning of chromosomes

DOEpatents

Lacks, S.A.

1995-07-18

A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

Phenotypic analysis of perennial airborne allergen-specific CD4+ T cells in atopic and non-atopic individuals.

PubMed

Crack, L R; Chan, H W; McPherson, T; Ogg, G S

2011-11-01

Accumulating evidence suggests that T cells play an important role in the pathogenesis of atopic dermatitis (AD); yet, little is known of the differentiation status of CD4+ T cells specific for common environmental allergens, such as the major cat allergen, Fel d 1. To determine the frequency, differentiation phenotype and function of circulating Fel d 1-specific CD4+ T cells in adult individuals with severe persistent AD in comparison with healthy controls. Using HLA class II tetrameric complexes based on a HLA-DPB1*0401-restricted Fel d 1 epitope, ex vivo and cultured T cell frequency and phenotype were analysed in individuals with AD and healthy controls. Cytokine secretion was measured by ex vivo and cultured IL-4 and IFN-γ ELISpots. Ex vivo Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopics and non-atopics express high levels of CCR7, CD62L, CD27 and CD28, placing the cells largely within the central memory subgroup. However, the functional phenotype was distinct, with greater IL-4 production from the cells derived from atopics, which correlated with disease severity. Circulating Fel d 1-specific DPB1*0401-restricted CD4+ T cells in both atopic and non-atopic donors maintain a central memory phenotype; however in atopics, the cells had greater Th2 effector function, compatible with a disease model of altered antigen delivery in atopic individuals. © 2011 Blackwell Publishing Ltd.

Genomic localization of the human gene encoding Dr1, a negative modulator of transcription of class II and class III genes.

PubMed

Purrello, M; Di Pietro, C; Rapisarda, A; Viola, A; Corsaro, C; Motta, S; Grzeschik, K H; Sichel, G

1996-01-01

Dr1 is a nuclear protein of 19 kDa that exists in the nucleoplasm as a homotetramer. By binding to TBP (the DNA-binding subunit of TFIID, and also a subunit of SL1 and TFIIIB), the protein blocks class II and class III preinitiation complex assembly, thus repressing the activity of the corresponding promoters. Since transcription of class I genes is unaffected by Dr1. it has been proposed that the protein may coordinate the expression of class I, class II and class III genes. By somatic cell genetics and fluorescence in situ hybridization, we have localized the gene (DR1), present in the genome of higher eukaryotes as a single copy, to human chromosome region 1p21-->p13. The nucleotide sequence conservation of the coding segment of the gene, as determined by Noah's ark blot analysis, and its ubiquitous transcription suggest that Dr1 has an important biological role, which could be related to the negative control of cell proliferation.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

PubMed

Laher, Faatima; Ranasinghe, Srinika; Porichis, Filippos; Mewalal, Nikoshia; Pretorius, Karyn; Ismail, Nasreen; Buus, Søren; Stryhn, Anette; Carrington, Mary; Walker, Bruce D; Ndung'u, Thumbi; Ndhlovu, Zaza M

2017-04-01

Immune control of viral infections is heavily dependent on helper CD4 + T cell function. However, the understanding of the contribution of HIV-specific CD4 + T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4 + T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4 + T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4 + T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4 + T cells in HIV controllers than progressors ( P = 0.0001), and these expanded Gag-specific CD4 + T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control ( r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4 + T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4 + T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4 + T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4 + T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4 + T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4 + T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4 + T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections. Copyright © 2017 American Society for Microbiology.

Class I and class II major histocompatibility molecules play a role in bone marrow-derived macrophage development

NASA Technical Reports Server (NTRS)

Armstrong, J. W.; Simske, S. J.; Beharka, A. A.; Balch, S.; Luttges, M. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

1994-01-01

Class I and class II major histocompatibility complex (MHC) molecules play significant roles in T cell development and immune function. We show that MHCI- and MHCII-deficient mice have low numbers of macrophage precursors and circulating monocytes, as well as abnormal bone marrow cell colony-stimulating factor type 1 secretion and bone composition. We suggest that MHCI and MHCII molecules play a significant role in macrophage development.

40 CFR Figure C-2 to Subpart C of... - Illustration of the Slope and Intercept Limits for Class II and Class III PM 2.5 Candidate...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Illustration of the Slope and Intercept Limits for Class II and Class III PM 2.5 Candidate Equivalent Methods C Figure C-2 to Subpart C of Part... Candidate Methods and Reference Methods Pt. 53, Subpt. C, Fig. C-2 Figure C-2 to Subpart C of Part 53...

40 CFR Figure C-2 to Subpart C of... - Illustration of the Slope and Intercept Limits for Class II and Class III PM 2.5 Candidate...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Illustration of the Slope and Intercept Limits for Class II and Class III PM 2.5 Candidate Equivalent Methods C Figure C-2 to Subpart C of Part... Candidate Methods and Reference Methods Pt. 53, Subpt. C, Fig. C-2 Figure C-2 to Subpart C of Part 53...

Congenital Stapes Ankylosis in Children: Surgical Findings and Results in 35 Cases.

PubMed

Vincent, Robert; Wegner, Inge; Kamalski, Digna M A; Bittermann, Arnold J N; Grolman, Wilko

2016-04-01

To evaluate surgical findings and hearing results in children undergoing middle ear surgery for congenital stapes ankylosis with or without other ossicular malformations (Teunissen and Cremers class I and class II malformations). A nonrandomized, nonblinded case series of prospectively collected data. A tertiary referral center. Twenty-eight consecutive pediatric patients who underwent 35 surgical procedures for congenital stapes ankylosis with or without other ossicular malformations and had available postoperative pure-tone audiometry. Primary stapedotomy with vein graft interposition and reconstruction with a Teflon piston, bucket handle prosthesis or total ossicular replacement prosthesis. Pre- and postoperative audiometric evaluation using four-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gaps (ABGs) were measured. Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months after surgery and at a yearly interval thereafter. Overall, a postoperative ABG closure of 10 dB or less was achieved in 73% of class I cases and in 50% of class II cases. A postoperative ABG closure of 20 dB or less was achieved in 77% of class I cases and 67% of class II cases. Postoperative sensorineural hearing loss occurred in one class I case (4%) and none of the class II cases. Stapedotomy is a safe and feasible treatment option in children with congenital stapes ankylosis.

Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

PubMed

Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

2017-08-01

Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.

40 CFR 148.1 - Purpose, scope and applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

....1 Section 148.1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.1 Purpose, scope and applicability. (a) This part identifies wastes that are restricted from disposal into Class I wells and defines those...

Therapeutic approach to Class II, Division 1 malocclusion with maxillary functional orthopedics

PubMed Central

de Bittencourt, Aristeu Corrêa; Saga, Armando Yukio; Pacheco, Ariel Adriano Reyes; Tanaka, Orlando

2015-01-01

INTRODUCTION: Interceptive treatment of Class II, Division 1 malocclusion is a challenge orthodontists commonly face due to the different growth patterns they come across and the different treatment strategies they have available. OBJECTIVE: To report five cases of interceptive orthodontics performed with the aid of Klammt's elastic open activator (KEOA) to treat Class II, Division 1 malocclusion. METHODS: Treatment comprehends one or two phases; and the use of functional orthopedic appliances, whenever properly recommended, is able to minimize dentoskeletal discrepancies with consequent improvement in facial esthetics during the first stage of mixed dentition. The triad of diagnosis, correct appliance manufacture and patient's compliance is imperative to allow KEOA to contribute to Class II malocclusion treatment. RESULTS: Cases reported herein showed significant improvement in skeletal, dental and profile aspects, as evinced by cephalometric analysis and clinical photographs taken before, during and after interceptive orthodontics. PMID:26352852

Orthodontic Camouflage Treatment in an Adult Patient with a Class II, Division 1 Malocclusion – A Case Report

PubMed Central

Naragond, Appasaheb; Kenganal, Smitha; Sagarkar, Roshan; Sugaradday

2013-01-01

Since so many decades, various treatment modalities have been presented for the treatment for the class II, div 1 malocclusions. In recent times, we have seen enormously increasing numbers of young adults who desire the shortest, cost effective and a non surgical correction of Class II malocclusions and they accept dental camouflage as a treatment option to mask the skeletal discrepancy. This case report presents one such case of a 22 year old non-growing female who had a skeletal Class II, division 1 malocclusion with an orthognathic maxilla, a retrognathic mandible, a negative VTO and an overjet of 12mm, who did not want a surgical treatment. We considered the camouflage treatment by extracting the upper first premolars. Following the treatment, a satisfactory result was achieved with an ideal, static and a functional occlusion, facial profile, smile and lip competence and stability of the treatment results. PMID:23543878

Duration of the peak of adolescent growth spurt in class i and ii malocclusion subjects using a cervical vertebrae maturation analysis.

PubMed

Salazar-Lazo, Rodrigo; Arriola-Guillén, Luis E; Flores-Mir, Carlos

2014-01-01

The aim of the present work was to determine the duration of the adolescent peak growth spurt using cervical vertebral maturation analysis in class I and II malocclusion subjects. The study was conducted on a sample which consisted of 154 lateral cephalograms of children and adolescents aged 9-15 years (84 females and 70 males). The evaluation of skeletal maturation stage was performed using a visual morphological analysis of CS3 and CS4 cervical vertebrae. The sagittal skeletal relation was evaluated according to Steiner analysis. Descriptive statistics were used to summarize chronological age in each malocclusion group and for each CS3 and CS4 skeletal maturation stage. Due to a lack of normal distribution, comparisons of CS3 and CS4 age intervals on class I and II subjects were compared using the Mann-Whitney U test for independent samples. The results show that the mean duration of the adolescent peak growth spurt was 10 months between CS3 and CS4 stages in class I malocclusion subjects, whereas in class II malocclusion patients the duration was 6 months. This difference of 4 months was statistically significant (p<0.001). Finally, a clinically significant difference of 4 months in the duration of the adolescent peak growth spurt for class I and II malocclusion subjects was identified.