bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between membrane IgM and the cytoskeleton involve the cytoplasmic domain of the immunoglobulin receptor
Authors: Park Jun Young , Jongstra‐Bilen Jenny
Published: March 2007

Cross‐linking induced interactions between the membrane form of immunoglobulin (mIg) and the cytoskeletal matrix have been described by several groups. To date, the function of mIgM association with the cytoskeleton is not yet understood. Delineation of the molecular basis of these interactions will be instrumental in elucidating their function. We have previously shown that the Igα/β heterodimer is not required for ligand‐induced mIgM binding to the cytoskeleton. In this study, we have investigated the role of other B cell‐specific proteins in mediating these interactions. For this, we expressed mIgM in the non‐hematopoietic human cervical carcinoma cell line HeLa S3 and verified the capacity of the surface‐expressed IgM to interact with the cytoskeletal matrix upon cross‐linking with anti‐μ chain antibodies. We show here that only the mIgM molecule itself and no other B cell‐specific protein(s) is required in mediating mIgM interactions with actin filaments. In an attempt to determine the cytoskeleton‐binding site of mIgM we investigated the role of the cytoplasmic tail of mIgM (KVK) in binding the receptor to actin‐based microfilaments. Using mutated forms of mIgM expressed in J558L cells, we show here that KVK plays a role in mediating these interactions. The absence of KVK did not, however, completely abrogate mIgM‐cytoskeletal interactions, suggesting that there are additional molecular requirements for the ligand‐induced mIgM binding to the cytoskeletal matrix.
Thiol modulation inhibits the interleukin (IL)‐1‐mediated activation of an IL‐1 receptor‐associated protein kinase and NF‐xB
Authors: Tewes Frank , Böl Gaby‐Fleur , Brigelius‐Flohé Regina
Published: March 2007

The interleukin‐1 receptor type I (IL‐1RI) is associated with other proteins thus forming a complex system by which IL‐1 exerts its various signals. The initiating event is still uncertain, but activation of a recently described receptor‐associated protein kinase is one of the earliest events detectable (Martin et al., Eur. J. Immunol. 1994. 24: 1566). IL‐1 signaling is commonly accompanied by oxidative processes and is thought to be subject to redox regulation. We therefore investigated whether the activation of the IL‐1RI‐associated protein kinase could be a target for redox regulation and whether an altered activity of the kinase could influence IL‐1‐mediated NF‐xB activation. A murine T cell line, EL4, was stimulated with IL‐1 with and without pretreatment with different compounds known to influence the cellular redox status. Thiol modifying agents like diamide, menadione, pyrrolidine dithiocarbamate (PDTC), diethyl dithiocarbamate or phenylarsine oxide inhibited the IL‐1‐induced activation of the IL‐1RI‐associated protein kinase. N‐Acetylcysteine, α,α′‐dipyridyl, aminotriazole or nitrofurantoin did not show any effect. The inhibition by PDTC was reversible unless glutathione synthesis was blocked by buthionine sulfoximine. The described conditions which inhibited or prevented the activation of the IL‐1RI‐associated kinase similarly impaired the activation of NF‐xB in EL4 cells. From these observations we conclude that free thiols in the IL‐1RI complex are essential for the activation of the IL‐1RI‐associated protein kinase and that this process is mandatory for IL‐1 signaling leading to NF‐xB activation.
Sequence analysis of rat integrin αE1 and αE2 subunits: Tissue expression reveals phenotypic similarities between intraepithelial lymphocytes and dendritic cells in lymph
Authors: Brenan Mary , Rees D. Jasper G.
Published: March 2007

The integrin αOX‐62 subunit is defined by the OX‐62 monoclonal antibody that was raised against rat dendritic cells in lymph (veiled cells) and shows properties similar to those of human αE2 that is predominantly expressed on intraepithelial lymphocytes. To clone αOX‐62, rat probes generated using primers specific for the human αE sequence were used to screen rat T cell cDNA libraries. cDNA clones encoding two similar but not identical α subunits that are closely related to but distinct from human αE were isolated. αE1 is predicted to be the rat homolog of mouse αM290 and αE2 corresponds to rat αOX‐62. Immunofluorescence analysis revealed that mouse αE1 and rat αE2 are expressed in dendritic epidermal T cells in the skin, intraepithelial lymphocytes in the small intestine and in cells with a dendritic morphology present at sites where γδ T cells occur in lymphoid organs. Unexpectedly, αE2 is co‐expressed with intracellular CD3‐δ and a 33‐kDa CD3 chain but not the T cell receptor in veiled cells. These findings suggest that veiled cells may be derived from a lymphoid precursor. Furthermore, veiled cells show phenotypic similarities to intraepithelial lymphocytes.
The 5′ hypermutation boundary of x chains is independent of local and neighbouring sequences and related to the distance from the initiation of transcription
Authors: Rada Cristina , Yélamos José , Dean Wendy , Milstein César
Published: March 2007

The hypermutation of antibody genes targets 1–2 kb of DNA which includes the rearranged V(D)J gene segments. The precise nature, location and limits of the targeted region are of considerable interest in terms of the mechanism of hypermutation. We have analyzed the frequency and distribution of mutations in the 5′ region of immunoglobulins using several modified x transgenes. We found that the position of the boundary, relative to the transcription initiation site, is not affected by the sequence of the V segment or by substituting the x chain promoter for a β‐globin promoter. Furthermore, the deletion of the leader intron (containing the hypermutation boundary) does not affect hypermutation per se, but shifts the boundary from the leader intron to the V region such that the distance between the boundary and the site of initiation of transcription remains constant. These results show that the position of the hypermutation boundary (about 185 bases downstream of the site of initiation of transcription) is not defined by the nucleotide sequence but rather by the distance to a fixed upstream position. Although mutations are also observed in the region upstream of the boundary, the frequency at which they occur is one order of magnitude lower relative to the frequency observed in the V segment. Nonetheless this upstream mutation rate remains more than two orders of magnitude higher than that of somatic genes. We discuss possible mechanisms explaining the nature and position of the boundary in the context of an error‐prone DNA repair model.
CD40 ligand inhibits Fas/CD95‐mediated apoptosis of human blood‐derived dendritic cells
Authors: Koppi Thelma A. , Tough‐Bement Teresa , Lewinsohn David M. , Lynch David H. , Alderson Mark R.
Published: March 2007

Dendritic cells (DC) are considered to be the most potent antigen‐presenting cells (APC) in the immune system. In this study, we analyzed the regulation of apoptosis of human peripheral blood‐derived DC. DC were generated from adherent peripheral blood mononuclear cells that had been cultured for 7 days with granulocyte‐macrophage colony‐stimulating factor and interleukin‐4. These cells displayed phenotypic properties of DC, including dendritic processes, expression of CD1a and lack of expression of CD14, and were very potent at presenting soluble antigens to T cells. Blood‐derived DC were demonstrated to express the Fas/CD95 antigen and an agonist antibody to CD95 strongly induced apoptotic cell death in these cells. Soluble trimeric CD40 ligand potently inhibited both CD95‐mediated and spontaneous apoptosis in DC. The data suggest that interactions between members of the tumor necrosis factor family of ligands expressed by T cells with their receptors on DC play an important role in the regulation of apoptosis in DC during antigen presentation and may, therefore, regulate the duration of T cell expansion and cytokine production.
High sensitivity of transgenic mice expressing soluble TNFR1 fusion protein to mycobacterial infections: Synergistic action of TNF and IFN‐γ in the differentiation of protective granulomas
Authors: Garcia Irène , Miyazaki Yoshitaka , Marchal Gilles , Lesslauer Werner , Vassalli Pierre
Published: March 2007

To investigate the role of tumor necrosis factor (TNF) in protective immune responses to Mycobacterium tuberculosis and M. bovis Bacillus Calmette Guérin (BCG), we have used transgenic mice unable to use TNF because of the expression of high amounts of a soluble TNF receptor (R) type I (sTNFR1) fusion protein, and studied resistance of these mice to infection by lethality assays, evaluation of bacterial recovery and histologic examination. These mice showed a strongly increased sensitivity to M. tuberculosis and BCG infections, with bacterial overgrowth and marked inhibition of macrophage differentiation within granulomas; after M. tuberculosis infection, this resulted in extensive lesions of caseous necrosis in the lung. To explore the respective roles of TNF and interferon (IFN)‐γ in resistance to BCG and granuloma differentiation, controls and sTNFR1‐transgenic mice were compared to IFN‐γR mutant mice and mice double defective in TNF and IFN‐γ activity (obtained by crossing transgenic and mutant mice). The three groups of deficient mice showed a strongly enhanced susceptibility to BCG infection, with the following decreasing order of sensitivity between groups: TNF + IFN‐γ → TNF → IFN‐γ‐deficient mice. The hepatic granulomas of IFN‐γR mutant mice were small and contained eosinophils but few differentiated macrophages; compared to those of sTNFR1‐transgenic mice, acid‐fast bacilli were less numerous within the macrophages. Granulomas of double‐deficient mice were strikingly different by their very large size and cellular content, made up large numbers of polymorphonuclears, eosinophils, and cells undergoing apoptosis, but without detectable differentiated macrophages; acid‐fast bacilli were spread in the lesions. These studies show the essential role of both TNF and IFN‐γ in the development, during mycobacterial infections, of protective granulomas containing highly differentiated macrophages capable of destroying ingested bacteria, and emphasize that these two cytokines act synergistically in granuloma formation.
IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (FcεRII)
Authors: Christie Gary , Barton Aisling , Bolognese Brian , Buckle Derek R. , Cook Richard M. , Hansbury Michael J. , Harper Gregory P. , Marshall Lisa A. , McCord Mark E. , Moulder Kevin , Murdock Paul R. , Seal Sheila M. , Spackman Vivienne M. , Weston Beverley J. , Mayer Ruth J.
Published: March 2007

CD23, the low‐affinity IgE receptor, is up‐regulated on interleukin (IL)‐4‐stimulated B cells and monocytes, with a concomitant increase in the release of soluble fragments of CD23 (sCD23) into the medium by proteolytic processing of the surface‐bound intact CD23. The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model in vivo was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein‐Barr virus‐transformed B cell line) cell membranes was inhibited by a broad‐spectrum matrix‐metalloprotease inhibitor, batimastat, with an IC50 of 0.15 μM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL‐4‐stimulated purified human monocytes with similar IC50. Batimastat inhibited IgE production from IL‐4/anti‐CD40‐stimulated human tonsil B cells as well as mouse splenic B cells in a manner consistent with inhibition of CD23 processing. Release of soluble fragments of CD23 in the cell supernatants of tonsil B cells was inhibited over the concentration range of 1–10 μM batimastat and intact cell surface CD23 was increased on mouse splenic B cells in the presence of these concentrations of batimastat. IgE production of IL‐4‐stimulated human peripheral blood mononuclear cells was also blocked by 1–10 μM batimastat, again with comparable inhibition of sCD23 release over the same concentration range. Finally, in a mouse model of IgE production, batimastat inhibited IgE production in response to ovalbumin challenge as determined by serum IgE levels. Taken together, the data support a role of CD23 in IgE production and point to CD23 processing to sCD23 as a therapeutically relevant control point in the regulation of IgE synthesis.
Pertussis toxin can replace T cell receptor signals that induce positive selection of CD8 T cells
Authors: Takahama Yousuke , Tokoro Yayoi , Sugawara Takehiko , Negishi Izumi , Nakauchi Hiromitsu
Published: March 2007

CD4+ helper T lymphocytes and CD8+ killer T lymphocytes are both generated in the thymus from common precursor cells expressing CD4 and CD8. The development of immature CD4+ CD8+ thymocytes into mature ‘single‐positive’ T cells requires T cell antigen‐receptor (TCR)‐mediated positive selection signals. Although it is known that the recognition specificity of TCR expressed by CD4+ CD8+ thymocytes determines their fate to become either CD4+ or CD8+ T cells, the molecular signals that direct precursor thymocytes to become CD4+ and CD8+ T cells are unclear. By using ZAP‐70− mutant thymus organ cultures in which T cell development is arrested at the CD4+ CD8+ thymocyte stage, the present study shows that distinct biochemical treatments can selectively restore the generation of mature CD4+ and CD8+ T cells, bypassing TCR‐induced positive selection signals. The combination of phorbol ester and ionomycin selectively restores the generation of CD4+CD8− TCRhigh cells consistent with previous results. On the other hand, we find that the generation of CD4− CD8+ TCRhigh cells is selectively induced by pertussis toxin. Interestingly, the signals generated by pertussis toxin, which increase Notch expression, can dominate the signals by phorbol ester and ionomycin, steering thymocyte development to CD8 lineage. These results indicate that distinct biochemical signals replace TCR signals that selectively induce positive selection of CD4+ and CD8+ T cells, and that biochemical treatment can manipulate the development and choice of CD4+ and CD8+ T cells.
Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vγ9/Vδ2 T cells in tumor immunity
Authors: Fisch Paul , Meuer Eva , Pende Daniela , Rothenfußer Simon , Viale Oriane , Kock Sylvia , Ferrone Soldano , Fradelizi Didier , Klein George , Moretta Lorenzo , Rammensee Hans‐Georg , Boon Thierry , Coulie Pierre , van der Bruggen Pierre
Published: March 2007

The Vγ9/Vδ2 T cell receptor (TCR) is expressed by most human γδ T cells. We show here that cytotoxic T lymphocytes of the Vγ9/Vδ2 subset, but not of the Vδ1 subset of human γδ T cells, express natural killer inhibitory receptors (KIR) with specificity for different HLA class I alleles that down‐regulate TCR‐mediated signaling in response to HLA class I‐expressing B cell lymphomas. Vγ9/Vδ2 T cell clones with a T helper cell phenotype lack KIR and produce lymphokines in response to most human B cell lymphomas, just as they do upon recognition of the HLA class l‐deficient human Burkitt's lymphoma Daudi. Thus, human Vγ9/Vδ2 T cells have an innate specificity for nonpolymorphic cell surface structures expressed by many lymphoma cells and their cytotoxic activity is controlled by KIR. These results imply a general role of human Vγ9/Vδ2 T cells in the defense against hematopoietic tumors that is distinct from NK cells.
A functional and kinetic comparison of antiviral effector and memory cytotoxic T lymphocyte populations in vivo and in vitro
Authors: Ehl Stephan , Klenerman Paul , Aichele Peter , Hengartner Hans , Zinkernagel Rolf M.
Published: March 2007

To analyze the critical parameters for effective antiviral cytotoxic T lymphocyte (CTL) activity in vivo, control of lymphocytic choriomeningitis virus (LCMV) infection in the spleen was studied after adoptive transfer of different spleen cell populations into preinfected recipients. The quantitative, qualitative and kinetic requirements for virus control were defined and related to in vitro assays to compare the antiviral protective function of CTL from naive, acutely infected and memory mice. Treatment of mice with an established but limited LCMV infection by adoptive transfer of spleen cells from acutely LCMV‐infected mice led to complete virus elimination mainly mediated by donor‐derived CD8+ T cell‐mediated, perforin‐dependent cytotoxicity. Since virus is continuously spreading and the number of infected target cells rapidly increases, the time until target cell lysis is achieved was critical: if release of viral progeny was not prevented early, additional time to perform effector function did not improve overall virus control. When the function of various cell populations was compared in this model, we found that CTL from naive and memory mice perform considerably less well than CTL from acutely infected mice. In vitro studies indicated that this is probably due to the fact that they can not fulfill the limiting time requirements for immediate antiviral protection: while CTL from acutely infected mice can perform lytic effector function immediately, memory CTL require a considerable reactivation time before they can lyse infected target cells. This reactivation does not necessarily involve cell division. These findings illustrate how critical time limitations are for CTL to mediate early control of a dynamic virus infection in vivo.
Functional characterization of receptor‐type protein tyrosine phosphatase CD148 (HPTPη/DEP‐1) in Fcγ receptor IIa signal transduction of human neutrophils
Authors: Hundt Matthias , Schmidt Reinhold E.
Published: March 2007

Activation of the 40‐kDa low‐affinity receptor for IgG (FcγRIIa, CD32) leads to tyrosine phosphorylation, increase of cytosolic free calcium concentration ([Ca2+]i), and production of superoxide anions (O2−) in neutrophils (PMN). It has been established that protein tyrosine kinases (PTK) and phosphatases (PTP) are essential for the regulation of intracellular signaling. CD45 is a type I receptor‐type protein tyrosine phosphatase (RPTP) with two PTP domains. Recently it has been demonstrated that co‐cross‐linking of CD45 modulates the signal transduction pathway of FcγRIIa in PMN. In contrast, the functional characteristics of CD148 (HPTPη/DEP‐1), a new RPTP with only one PTP domain, is unknown. CD148 is expressed on PMN in slightly lower density than CD45, and in higher density than on lymphocytes. [Ca2+]i measured with fluo‐3‐loaded PMN by flow cytometry and O2− production determined by lucigenin‐dependent chemiluminescence were inhibited by co‐cross‐linking of CD45 with FcγRIIa in comparison to isotype control monoclonal antibody (mAb). In contrast, preincubation with CD148 mAb 143‐41 abolished O2− generation, but did not inhibit [Ca2+]i rise. In summary, both clustered human RPTP, CD45 and CD148, inhibit FcγRIIa‐induced O2− production in PMN, but they differ in regulation of [Ca2+]i. Therefore, it is suggested that co‐cross‐linking of FcγRII with CD45 and CD148 leads to dephosphorylation of different substrates. These distinct functional capacities may be important for differential regulation of FcγR signaling by currently unknown ligands.
Photochemical Generation of Cyclophanes from 1,3,5‐Trisubstituted Benzenes with Chalcone Chromophores
Authors: Karpuk Elena , Schollmeyer Dieter , Meier Herbert
Published: March 2007

(E,E,E)‐1,3,5‐Tricinnamoylbenzene (7a) photodimerizes in solution to the [4.4.4](1,3,5)cyclophane 8a. The process consists of three consecutive steps in which cisoid enone conformations of 7a react in regio‐ and stereoselective anti‐head‐to‐head cycloadditions. (E,E,E)‐1,3,5‐Tris(3‐oxo‐3‐phenylpropenyl)benzene (13a), an isomer of 7 with reversed enone units, shows a single [2π+2π] cycloaddition of the same type. Due to steric reasons, it is afterwards not capable of intramolecular processes and oligomerizes by intermolecular photocycloadditions. Photolyses in the crystalline state yield dimers by topochemically controlled syn‐head‐to‐tail processes (7a → 10a, 13a → 15a). An efficient dimerization of 13a takes place, although the distance between the olefin centers exceeds with 5.07 Å by far the limit postulated in Schmidt's rule.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Olefin Metathesis: A Reversible Stimulus for a Conformational Switch
Authors: Garcia M.‐Elisa Juarez , Fröhlich Ute , Koert Ulrich
Published: March 2007

A ring‐closing olefin metathesis (RCM) to an eight‐membered ring is suitable to induce a conformational switch of a 2,3,6,7‐tetrasubstituted cis‐decalin. The double‐ring flip of the decalin scaffold can be reversed by a ring‐opening metathesis. The corresponding RCM to a 14‐membered ring does not force the double ring flip to occur. A ring‐size competition experiment resulted in the exclusive formation of an eight‐membered ring. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Myelin transcription factor 1 (Myt1) expression in demyelinated lesions of rodent and human CNS
Authors: Vana Adam C. , Lucchinetti Claudia F. , Le Tuan Q. , Armstrong Regina C.
Published: March 2007

Myelin transcription factor 1 (Myt1) is a zinc‐finger DNA binding protein that influences developing oligodendrocyte progenitor (OP) cell proliferation, differentiation, and myelin gene transcription in vitro. The potential of Myt1 to play a role in OP responses leading to remyelination was examined using murine hepatitis virus strain A59 (MHV) to induce spinal cord demyelination and potential relevance to human pathology was evaluated in multiple sclerosis (MS) lesions. In MHV‐infected mice, the density of Myt1 expressing cells markedly increased in lesioned areas of spinal cord white matter. Myt1 expressing cells proliferated most extensively during active demyelination and subsequently accumulated to maximal levels during early remyelination. Cells with nuclear Myt1 immunoreactivity were mainly OP cells, identified by co‐localization with platelet‐derived growth factor alpha receptor, with additional phenotypes being either oligodendrocytes or neural stem cells, identified by CC1 antigen and Musashi1, respectively. The density of OP cells expressing Myt1 was significantly increased in white matter of MHV‐infected mice during demyelination and early remyelination then as remyelination advanced the values returned to levels comparable to PBS‐injected control mice. In MHV lesions, Myt1 was not expressed in astrocytes, lymphocytes, or macrophage/microglial cells. MS lesions demonstrated increased Myt1 expression in both the periplaque white matter adjacent to lesions and within early remyelinating lesions. These results suggesta potential role for Myt1 in the regeneration of oligodendrocyte lineage cells in response to demyelination. © 2007 Wiley‐Liss, Inc.
Anionic ring‐opening polymerization of small phosphorus heterocycles and their borane adducts: An ab initio investigation
Authors: Coote Michelle L. , Hodgson Jennifer L. , Krenske Elizabeth H. , Wild S. Bruce
Published: March 2007

The kinetics and thermodynamics of anionic ring‐opening reactions of phosphiranes, phosphetanes, and phospholanes and their borane adducts have been studied by high‐level ab initio procedures. For the free heterocycles, model propagation reactions involving nucleophilic attack by Me2P− at the ring α‐carbon were found to be feasible for the three‐ and four‐membered rings, but not for the five‐membered ring. For the borane adducts, nucleophilic attack by Me2(BH3)P− was only facile for the three‐membered ring, despite an increased thermodynamic tendency toward ring opening for the borane adducts of both the three‐ and four‐membered rings. The formation constants of the borane adducts of methylphosphirane and methylphosphetane were K = 2.6 × 1013 L mol−1 and K = 1.2 × 1020 L mol−1, respectively. A Marcus analysis of the ring‐opening reactions of methylphosphirane, methylphosphetane, and their borane adducts showed that the release of ring strain and an “additional factor'' contribute to rate enhancement compared with their strain‐free analogues. The additional factor was larger for the three‐membered rings than for the four‐membered rings and was larger in the free heterocycles than in their borane adducts. The additional factor is complex in origin and appears to reflect an increase in the separation between the bonding and antibonding orbitals of the breaking bond on going from the three‐membered rings to the four‐membered rings, and on going from the free heterocycles to the borane adducts. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:118–128, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20323
Dynamic aspects of hypervalent compounds effected by the formation of three center‐four electron bond in heteroatoms
Authors: Akiba Kin‐ya , Yamamoto Yohsuke
Published: March 2007

Hypervalent bond (three center‐four electron bond: 3c‐4e) is the central feature of the structure and reactivity of hypervalent compounds. The SSS bond of thiathiophthene, the so‐called no‐bond resonance compound, is realized as one of the examples of 3c‐4e bond centered at the sulfur atom (10‐S‐3). A variety of reactions such as cycloaddition‐elimination, bond‐switching rearrangement, and bond‐switching equilibration of sulfur‐containing heterocycles are exemplified to proceed through the presence of hypervalent 10‐S‐3 species. In the transition state of edge inversion, it is predicted that a vacant p‐type orbital is perpendicular to the square planar species. Antimony(III) and bismuth(III) compounds bearing a bidentate Martin ligand and a phenyl, or 2‐dimethylaminomethylphenyl, or 2,6‐bis(dimethylaminomethyl)phenyl group were prepared. The rates of inversion of these compounds at the central atom of Sb or Bi were accelerated significantly by the coordination of the dimethylamino group and also of pyridine from the solvent, where 3c‐4e bond is formed by the coordination to stabilize the transition state. Finally, the presence of rapid bond‐switching equilibration between NB···N bond of 1,8‐bis(dimethylamino)‐9‐(substituted)borylanthracenes was shown to proceed through 10‐B‐5 species at the transition state. It is concluded that the bond‐switching equilibration takes place as a piston rod in the range of 1.32 Å. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:161–175, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20326
Halogen bonding and isostructurality in 2,4,6‐tris(2‐halophenoxy)‐1,3,5‐triazines
Authors: Saha Binoy K. , Nangia Ashwini
Published: March 2007

Crystal structures of 2,4,6‐tris(2‐halophenoxy)‐1,3,5‐triazines (halo = fluoro, chloro, bromo, iodo; 2‐XPOT) are discussed in the background of 3‐halophenoxy (3‐XPOT) and 4‐halophenoxy (4‐XPOT) structures. Among inter‐halogen interactions, the electrostatic L‐shaped type II interactions are generally shorter than the inversion‐related type I geometry in 2‐halo compounds. π‐Stacking of triazine rings at van der Waals separation (∼3.5 Å) makes the well‐known Piedfort Unit assembly and the halogen atoms form a trimer motif. 2‐FPOT and 2‐ClPOT are 2D isostructural but there are differences in the complete 3D molecular packing. 2‐BrPOT and 2‐IPOT are a 3D isostructural pair and their isomorphous unit cells have a similarity index of 0.008. The position of the halogen atom causes structural differences in 2‐, 3‐, and 4‐XPOT compounds, with the para‐series showing guest inclusion and the ortho‐ and meta‐compounds having single‐component close‐packed structures. The Cambridge Structural Database is analyzed for structural mimicry upon halogen GRoup eXchange (GRX). Chloro‐, bromo‐, and iodo‐substituted compounds of the same molecule (56 clusters) are isostructural in 30% cases, Cl/Br are identical in 66% pairs, and Br/I in 50% examples of the subdatabase. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:185–194, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20328
Treatment of contaminated bone defects with clindamycin‐reconstituted bone xenograft‐composites
Authors: Bi Long , Hu Yunyu , Fan Hongbin , Meng Guolin , Liu Jian , Li Dan , Lv Rong
Published: March 2007

Contaminated or infected bone defects and osteomyelitis after trauma are frequently encountered in clinical practice. It is difficult to make a successful bone graft and control infection at the same time. To find a better method to resolve this dilemma, we prepared a novel clindamycin‐reconstituted bone xenograft‐composite (C‐RBX‐C) that comprised of crude bBMP (bovine bone morphogenetic protein), clindamycin, and cancellous bone scaffold, and investigated the morphology, biocompatibility, antibiotic release profile and osteoinductive potential of this composite. The ultrastructure of C‐RBX‐C was evaluated by scanning electron microscopy; the biocompatibility and osteoinductive potential were assessed by testing ectopic implants. The antibiotic release profile was evaluated using a disc‐diffusion assay. Finally, this composite was used to repair a Staphylococcus aureus contaminated bone defect in a rabbit model. 16 weeks after the implantation of C‐RBX‐C, the radial defect had been completely recuperated, with significantly better formation of lamellar bone and recanalization of the marrow cavity, than in the controls (scaffolds without clindamycin or bBMP). These results demonstrate that our novel composite, with its concomitant osteoinductive and antibiotic properties, has significant potential for the treatment of contaminated or infected bone defects and osteomyelitis. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007
Linear regression model of DNA sequences and its application
Authors: Dai Qi , Liu Xiao‐Qing , Wang Tian‐Ming , Vukicevic Damir
Published: March 2007

We constructed six new models to analyze the DNA sequences. First, we regarded a DNA primary sequence as a random process in t and gave three ways to define nucleotides' random distribution functions. We extracted some parameters from the linear model and analyzed the changes of the nucleotides' distributions. In order to facilitate the comparison of DNA sequences, we proposed two ways to measure their similarities. Finally, we compared the six models by analyzing the similarities of the DNA primary sequences presented in Table 1 and selected the optimal one. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
A DFT study on the dimerization of C62, H2C62, and F2C62
Authors: Qiang Hou Jin , Seok Kang Hong
Published: March 2007

On the basis of calculations using the density functional theory, we show that C62, a recently synthesized nonclassical fullerene, will presumably undergo dimerization with various isomers at elevated temperatures. This is shown by calculating the dimerization energy and the activation barrier of the dimerization. Eight possible isomers of the dimer were identified, all of which are more stable than the two isolated monomers. The relative stability of various isomers depends upon the kind of CC bonds within the four‐membered carbon ring involved in the dimerization. In addition, similar calculations were performed for the monomers and dimers of H2C62 and F2C62. Six isomers were identified for each of the dimers. Although less pronounced than the case of the C62 dimer, all isomers of the H2C62 dimer are appreciably more stable than the individual monomers. Although a large steric repulsion due to F atoms significantly reduces the stability of F2C62 dimer, its two isomers are still more stable than separate monomers. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
A dynamic lattice searching method with constructed core for optimization of large lennard‐jones clusters
Authors: Yang Xiaoli , Cai Wensheng , Shao Xueguang
Published: March 2007

A variation of the previous dynamic lattice searching (DLS) method, named as DLS with constructed core (DLSc), was proposed for structural optimization of Lennard‐Jones (LJ) clusters. In the new method, the starting random structure is generated with an icosahedron or a decahedron as a core. For a cluster with n shells, the atoms in the inner n − 2 shells are set as a fixed core, and the remaining atoms in the outer 2 shells are optimized by DLS. With applications of DLSc to optimization of LJ100–200 and LJ660–670, it was found that all the putative global minima can be obtained by using the DLSc method, and the method was proved to be high efficient compared with the previous DLS, because the searching space is reduced by the use of the fixed core. However, although DLSc is still an unbiased approach for smaller LJ clusters, it turned out to be biased for large ones. Further works are still needed to make it to be a more general method for cluster optimization problem. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
Correlations between anti‐albumin antibodies and HBsAG in hepatic patients
Authors: Lenkei R. , Babes V. T. , Dan M. E. , Mustea A. , Dobre I.
Published: March 2007

A new category of autoantibodies ‐ antipolymerized albumin antibodies (AAA) ‐ was discovered in 1974. Studies performed from 1974 to 1976 showed their diagnosis and prognostic values in hepatic diseases; the AAA tests [immunodiffusion (ID) and hemagglutination (HS)] made possible a good estimation of the total liver cell function. Without being specific for a viral hepatitis B infection, highly significant linear correlations were found for AAA precipitin and agglutinin positivities with presence of HBsAg. High titre of AAA agglutinins unaccompanied by a positive ID test, characterise the “healthy carrier” of the HBsAg, while the isolated AAA positivity in ID is met in more severe, long‐standing hepatic diseases.
A persistent infection of baby hamster kidney‐21 cells with mumps virus and the role of temperature‐sensitive variants
Authors: Truant Allan L. , Hallum Jules V.
Published: March 2007

A persistent infection of baby hamster kidney‐21 (BHK‐21) cells with mumps virus (BHKpi) was maintained for over 60 cell passages in the absence of antiserum. Viral persistence was demonstrated in the cultures by hemadsorption, immunofluorescence, multinucleate syncytia, and released mumps virus at the level of 102–103 fluorescent focus‐forming units/ml. No detectable levels of interferon were found in cultures persistently infected with mumps virus. Approximately 85–95% of the cells contained viral antigens. Nuclear fluorescence was observed in the persistently infected cells. Mumps virus from persistently infected cultures (MuVpi) was more heat‐labile than wild‐type mumps (MuVo) when subjected to 40°C. BHKpi cells had a more rapid doubling time and a higher cloning efficiency in soft agar in comparison to BHK‐21 cells. MuVpi was also found to be temperature‐sensitive. The temperature‐sensitivity of MuVpi was determined by the efficiency of plating at 33° and 39°C. MuVpi readily established a persistent infection in BHK‐21 cells with less cytopathology than MuVo, and released temperature‐sensitive virus.
Rotavirus infections in adults in association with acute gastroenteritis
Authors: von Bonsdorff C.‐H. , Hovi T. , Mäkelä P. , Mörttinen A.
Published: March 2007

During an epidemic of acute gastroenteritis in Helsinki, in March – May 1976, 18 out of 40 adult patients showed electron microscopic and/or serologic evidence for rotavirus infection. Rotavirus was most frequently seen in the fecal suspensions from 2 to 6 days after the onset of the symptoms but persisted in one patient for as long as 10 days. An increase in the complement‐fixing (CF) serum antibody titers against the related Nebraska calf diarrhea virus (NCDV), or an initially high titer and subsequent significant decrease, was seen in all but one patient with rotavirus‐positive feces, and in 6 additional patients. This suggests that using electron microscopy as the only diagnostic procedure a considerable number of rotavirus infections in adults remain undectected.

Immune response against autologous or homologous rotavirus was also documented by immunoelectron microscopy. Complement‐fixing antibody titers against NCDV decreased significantly from the convalescence values over a half‐year observation period, but still remained clearly above the titers of a gastroenteritis‐negative control population.
Experimental respiratory syncytial virus pneumonia in cebus monkeys
Authors: Richardson Linda S. , Belshe Robert B. , Sly D. Lewis , London William T. , Prevar David A. , Camargo Ena , Chanock Robert M.
Published: March 2007

Into 14 juvenile cebus monkeys that lacked serum antibodies for RS virus 108 plaque‐forming units (pfu) of wild‐type respiratory syncytial (RS) virus were inoculated transtracheally. Roentgenographic evidence of pneumonia developed in 13 of 14 infected animals. Gross pathologic changes occurred in each of the 13 monkeys that were sacrificed. Patchy areas of red consolidation were seen in the lower lobes 24 hours after inoculation, and there was progression to gray consolidation seven days later. Each of the infected animals had histologic evidence of interstitial pneumonia. Changes were detected in the lung as early as 24 hours after inoculation; they consisted primarily of infiltration of the alveolar wall. By the fourth to sixth day after inoculation there was marked interstitial thickening, pulmonary consolidation, formation of multinucleated giant cells and development of eosinophilic cytoplasmic inclusion bodies within alveolar cells. RS viral antigens, detected by indirect immunofluorescence, were distributed throughout cells of the alveolar wall and the bronchiolar epithelium. The virus grew to highest titer in the lungs on the fourth to sixth day after inoculation; up to 108 pfu/gram of tissue were detected. The cebus monkey represents the first experimental host to develop extensive pulmonary lesions during infection with respiratory syncytial virus.
Differential activation of hepatitis B DNA polymerase by detergent and salt
Authors: Hirschman Shalom Z. , Gerber Michael , Garfinkel Esther
Published: March 2007

Three patterns of activity were evident when the differential activation of the DNA polymerase associated with serum Dane particles by nonionic detergent and salt was investigated. The patterns were obtained by plotting the increase in enzyme activity mediated by the detergent Nonidet P‐40 (NP‐40) in increasing concentrations of KCl compared to the activity observed in the absence of detergent. The pattern of differential activity of hepatitis B (HB) DNA polymerase in detergent and salt was altered by subjecting the HBAg preparations to shearing forces. Hepatitis B DNA polymerase activity was stable even in NP‐40 concentrations as high as 10%. In addition to hepatitis B DNA polymerase, DNA polymerase activated by calf thymus DNA was found in pellets containing Dane particles. The latter DNA polymerase activity was also activated by NP‐40 and was not decreased by DNAse; this DNA polymerase coprecipitated with hepatitis B antigen (HBAg) upon addition of anti‐HBs. However, the DNA polymerase activated by calf thymus DNA was inhibited by 0.4 M KCl. Electron microscopic observations of serum Dane particles in 0.4 M KCl showed no alterations of morphology of these particles when compared to particles in low‐salt buffer. The data indicated that KCl activated HB DNA polymerase by a different mechanism from that of shear or NP‐40, which removed the surface antigen coat from the Dane particles.
Steroid hormone alteration of herpes simplex virus type 1 replication
Authors: Notter Mary F. D. , Docherty John J.
Published: March 2007

The effect of steroid hormones on herpes simplex virus type 1 replication was examined. Virus replication studies revealed that various concentrations of prednisolone, hydrocortisone, dexamethasone, or progesterone could decrease virus yields up to a maximum of 99%. Using isopycnic centrifugation in CsCl to separate viral from cell DNA, it was found that virus‐specific DNA synthesis was decreased by 30 to 100% depending on the hormone and concentration used. Cell‐specific DNA synthesis was also adversely affected, but this did not alter cell viability or plating efficiency.
Subacute encephalitis and hydrocephalus in hamsters caused by measles virus from persistently infected cell cultures
Authors: Norrby Erling , Kristensson Kirster
Published: March 2007

Newborn hamsters were inoculated intracerebrally with measles virus materials from Lu 106 and Vero carrier cell lines. Extracellular and cell‐associated materials from cultures incubated at 37°C and at 33°C were used. The lower temperature allows accentuated virus replication. No animals contracted acute encephalitis, but 8 animals developed advanced neurological disease (unsteady gait, serial myoclonic jerks, hypoactivity) 79 to 212 days after injection. Seven out of these 8 animals belonged to a group of 50 animals, which had been inoculated with cell‐associated material from cultures incubated at 33°C. Viral antigen and nucleocapsids were found in neurons and glial cells from diseased animals, which showed degenerative changes and inflammation, particularly in the mesencephalon. Some of these animals also had hydrocephalus, which, however, also occurred in many apparently healthy animals. Also this pathological alteration occurred most frequently (5 out of 11 animals examined 9–10 months after inoculation) in hamsters receiving cell‐associated material from carrier cultures incubated at 33°C. Possible mechanisms for the appearance of hydrocephalus are discussed.
Prevalence of antibody to the hepatitis A virus in a large institution for the mentally retarded
Authors: Lehmann Noreen I. , Sharma D. L. B. , Gust Ian D.
Published: March 2007

The prevalence of antibody to hepatitis A virus (anti‐HAV) was determined in 854 people living in a large institution for the mentally retarded in Melbourne. Altogether 638 (74.4%) of the subjects were found to have specific antibody detectable by solid‐phase radioimmunoassay (SPRIA). No difference in antibody prevalence was observed between males and females; however, the prevalence was higher among subjects with Down syndrome (84.1%) than those of other forms of mental retardation (72.8%). In both groups there was an increase in prevalence of antibody with increasing age and duration of institutionalization. When compared with the open community, patients in this Institution have a higher prevalence of antibody and appear to acquire their infections at an earlier age.
Reduction of herpes simplex virus‐type 2 plaque formation by urea
Authors: Tumilowicz Joseph J. , Latlief Mildred A.
Published: March 2007

The effect of urea on plaque formation by herpes simplex virus type 2 (HSV‐2) was examined in two systems at concentrations within or approximating the range found in human urine. Approximately 7‐10 mg urea/ml, added 2, 4, or 8 hours after infection, reduced plaque formation by 50% in African green monkey kidney cells. The growth of this system was affected slightly by continuous treatment with urea at 7–10 mg/ml. Plaque formation was reduced in the monkey kidney system, albeit diminishingly, even after addition of urea 12 hours after infection. In the human lung fibroblast system, urea at 10 mg/ml reduced plaque numbers by 50% but depressed the growth of cells completely.
Astrovirus infection in volunteers
Authors: Kurtz J. B. , Lee T. W. , Craig J. W. , Reed Sylvia E.
Published: March 2007

An extract and a filtrate prepared from feces of a child with mild gastroenteritis were shown by electron microscopy to contain numerous astrovirus particles and were given to eight volunteers by mouth. One subject developed diarrheal illness and concurrently shed large amounts of astrovirus in feces, and one other had mild constitutional symptoms with a lower level of virus shedding. Nine other volunteers were given fecal filtrate from the volunteer with diarrhea, and astrovirus shedding subsequently occurred in two of them. The syndrome accompanying virus shedding appeared distinct from that associated with the “W” agent in previous experiments. Thirteen of 16 astrovirus‐inoculated subjects subsequently developed a rise in titer of the homologous antibody in serum. It was concluded that astrovirus causes a transmissible infection that is of low pathogenicity for adults. Immunofluorescence of human embryo kidney cells inoculated with astrovirus and shown by electron microscopy to contain 28 nm virus‐like particles was used both to detect virus in feces and to assay astrovirus antibody.
HBeAg and anti‐hbe detection by radioimmunoassay: Correlation with vertical transmission of hepatitis B virus in Taiwan
Authors: Stevens Cladd E. , Neurath Robert A. , Beasley R. Palmer , Szmuness Wolf
Published: March 2007

A sensitive radioimmunoassay technique was used to detect hepatitis B e antigen (HBeAg). A strong correlation was found between HBeAg positivity of the serum of hepatitis B surface antigen (HBsAg) carrier women in Taiwan and the subsequent development of surface antigenemia in their babies. All babies who became chronic HBsAg carriers were born to HbeAg positive women, maternal HBeAg positivity being a better prior indication of chronic antigenemia developing in the baby than the HBsAg titer in the mother's serum.
Hemolysis‐in‐gel test in immunity surveys and diagnosis of rubella
Authors: Väänänen Pertti , Vaheri Antti
Published: March 2007

The hemolysis‐in‐gel (HIG) technique was adapted for rubella antibody determinations. Use of sucrose gradient purified virus and its coupling with CrCl3 to chicken erythrocytes resulted in gel plates that could be stored for several weeks and were suitable for reproducible antibody determinations. In a serological survey of young healthy adults the HIG values (range > 2–13 mm) were in close correlation to those obtained by the HI test (> 10 to 320). The HIG test seems well suited for screening the need of vaccination. Seronegative sera (HIG > 2, HI> 10) gave without heat inactivation hemolysis zones ranging from 4 to 6.5 mm. Although the present rubella HIG test did not measure IgM antibodies, the test, by virtue of its accuracy and sensitivity — extending to antibody levels corresponding to HI titers 2–10 — provides a simpler and more rapid means for diagnosis of rubella infections than the conventional HI and CF tests.
Hepatitis B core antibody in volunteer blood donors: Comparison of radioimmunoassay and indirect immunofluorescence
Authors: Katchaki J. N. , Siem T. H. , Brouwer R.
Published: March 2007

The results of a pilot study on the prevalence of anti‐HBc in HBsAg negative volunteer blood donors are presented.

Two techniques for anti‐HBc determination were compared — radio—immunoassay (RIA) and indirect immunofluorescence (IF). In a panel of 56 sera with known HBV markers, RIA was found to be significantly more sensitive than IF, and both techniques were specific. Out of 2,000 HBsAg negative blood donor sera tested by RIA,46 (2.3%) were found positive for anti‐HBc. In 24/24 sera, the specificity of the anti‐HBc was confirmed. Also 37/46 (80.4%) anti‐HBc positives were found positive for anti‐HBs, leaving 9/2, OOC (0.4%) blood donors positive only for anti‐HBc.

It is concluded that it would be premature to advocate the introduction of anti‐HBc as a routine screening test of blood donors.
A new principle for the detection of specific IgM antibodies applied in an ELISA for hepatitis a
Authors: Duermeyer W. , Wielaard F. , van der Veen J.
Published: March 2007

A new test principle for the detection of specific IgM‐class antibodies was developed and applied in an Enzyme‐Linked Immuno Sorbent Assay (ELISA) for the detection of hepatitis A IgM antibodies. A solid phase coated with anti IgM was incubated successively with serum sample, specific antigen, and enzymelabeled F (ab')2 fragments from IgG antibodies against the antigen and enzyme substrate.

F(ab')2 fragments were used to avoid interference with rheumatoid factor. Specificity and sensitivity are very high. This test principle appears generally applicable in the diagnosis of infectious and parasitic diseases by testing only one serum sample.