bluuebunny/crossref_metadata_2025_split huggingface dataset:
The X‐linked immunodeficiency defect in the mouse is corrected by expression of human Bruton's tyrosine kinase from a yeast artificial chromosome transgene
Authors: Maas Alex , Dingjan Gemma M. , Savelkoul Huub F. J. , Kinnon Christine , Grosveld Frank , Hendriks Rudolf W. 
Published: March 2007

AbstractMutations in the gene for Bruton's tyrosine kinase result in the B cell differentiation defects X‐linked agammaglobulinemia in man and X‐linked immunodeficiency in mice. Here we describ the generation of two yeast artificial chromosome (YAC)‐transgenic mouse strains in which high‐level expression of human Btk is provided by endogenous regulatory cis‐acting elements that are present on a 340‐kb transgene, Yc340‐hBtk. The expression pattern of the transgenic human Btk was found to parallel that of the endogenous murine gene. When the Yc340‐hBtk‐transgenic mice were mated onto a Btk‐deficient background, the xid B cell defects were fully corrected: conventional and CD5+ B‐1 B cells were present in normal numbers, serum IgM and IgG3 levels as well as responses to T cell‐independent type II antigens were in the normal ranges. In vivo competition experiments in Btk+/− female mice demonstrated that in the conventional B cell population the Yc340‐hBtk transgene could fully compensate the absence of expression of endogenous murine Btk. We conclude that in the YAC‐transgenic mice Btk is appropriately expressed in the context of native regulatory sequences.
Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals
Authors: Mußmann Rainer , Courtet Michèle , Schwager Joseph , Du Pasquier Louis 
Published: March 2007

AbstractImmunoglobulin (Ig) heavy chain class switch recombination has been studied at the DNA level in a non‐mammalian vertebrate, the amphibian Xenopus. A switch (S) region of about 5 kb has been identified in the JH‐Cμ intron of the Ig heavy chain locus in Xenopus. Sμ contains 23 repeats approximately 150 bp long. Each repeat consists of internal shorter repeats and palindromic sequences, such as AGCT, which they share with mammalian switch regions. A deletion of the μ gene and the joining of the S regions of μ and χ occurs in B cells expressing IgX, one of the two non‐μ isotypes in Xenopus. Sx shows no sequence homology with Sμ and is characterized by 16 and 121 bp repeats and a high frequency of CATG, AGCA and TGCA palindromes. Both IgM and IgX S regions are AT rich and not GC rich like mammalian S regions. Recombination occurs, most of the time, at positions (microsites) where a single‐stranded DNA folding program predicts the transition from a stem to a loop structure. This feature is conserved in most mammalian switch junctions which points to the general existence and involvement of microsites at one step of the determination of the recombination breakpoint. The recombinogenic nature of the switch regions is therefore linked to its structure rather than to its base composition, the repetitive occurrence of palindromes being essential at creating many microsites.
Requirement of a second signal via protein kinase C or protein kinase A for maximal expression of CD40 ligand. Involvement of transcriptional and posttranscriptional mechanisms
Authors: Suárez Ana , Mozo Lourdes , Gayo Abel , Zamorano José , Gutierrez Carmen 
Published: March 2007

AbstractHigh levels of CD40 ligand (CD40L) protein expression are induced on native T cells by increasing the intracellular Ca2+ concentration. In the present study we have shown that ionomycin induces CD40L gene transcription leading to mRNA accumulation which translates to high levels of protein expression. Conversely, agents which increase the intracellular levels of cyclic AMP (cAMP), such as prostaglandin E2 (PGE2) or dibutyryl cyclic AMP (dbcAMP), were unable to induce CD40L expression on T lymphocytes. Cell activation by phorbol 12‐myristate 13‐acetate (PMA) treatment had a slight effect on increasing CD40L mRNA and protein levels. However, PMA and dbcAMP synergized with ionomycin to significantly increase and to prolong the CD40L expression. Nuclear run‐on assays revealed that PMA, but not dbcAMP, increased threefold the CD40L gene transcription rate induced by ionomycin. This effect was independent of de novo protein synthesis. In addition, at a posttranscriptional level, both reagents synergized with the Ca2+ ionophore to prolong the CD40L mRNA half‐life by a mechanism which was also independent of de novo protein synthesis. Moreover, when transcription was blocked with actinomycin D, an increment of the CD40L transcript levels induced by PMA or dbcAMP on ionomycin‐treated cells was observed in the presence of cycloheximide. This probably means that newly synthesized protein may contribute to the CD40L mRNA destabilization. In summary, these data show that PMA and dbcAMP synergized with ionomycin to increase the CD40L mRNA and protein levels. The up‐regulatory effect of PMA was accomplished at a transcriptional and posttranscriptional level, whereas dbcAMP exerted its synergistic effect exclusively at a posttranscriptional level.
Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co‐stimulatory molecules
Authors: Aiba Setsuya , Terunuma Atsushi , Manome Hideaki , Tagami Hachiro 
Published: March 2007

AbstractAfter application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co‐stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte‐derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte‐derived DC showed at least phenotypic characteristics and a response to TNF‐α similar to LC, we added various chemicals, i.e. dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte‐derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA‐DR antigen, and interleukin (IL)‐1β production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA‐DR and the production of IL‐6 and tumor necrosis factor (TNF)‐α. In addition, the up‐regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti‐IL‐1β or anti‐TNF‐α antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporin, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co‐stimulatory molecules and their production of cytokines with a resultant change in antigen‐presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.
Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: Reactivity to the extracellular domain of MOG is directed against three main regions
Authors: de Rosbo Nicole Kerlero , Hoffman Michael , Mendel Itzhack , Yust Israel , Kaye Joel , Bakimer Ronit , Flechter Shlomo , Abramsky Oded , Milo Roni , Karni Araon , Ben‐Nun Avraham 
Published: March 2007

AbstractOur previous analysis of the T cell reactivity to myelin antigens in a group of 24 patients with multiple sclerosis (MS) and 16 control individuals revealed that the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) predominates in MS over that to myelin basic protein (MBP), proteolipid protein or myelin‐associated glycoprotein, suggesting a prevalent role for the autoimmune response to MOG in the pathogenesis of MS. Using a recombinant human MOG (rhMOG) preparation corresponding to the extracellular immunoglobulin‐like domain of the MOG molecule, we have now analyzed another group of 52 MS patients and 49 control individuals for reactivity of their peripheral blood lymphocytes (PBL) to rhMOG and to MBP concomitantly. Of the 52 MS patients tested 24 responded to MOG and 10 out of 49 responded to MBP, whereas only 5 MOG‐reactive and 4 MBP‐reactive control individuals were detected out of the 49 tested. These results are therefore highly confirmatory of the predominant reactivity to MOG in MS. The analysis of the primary proliferative response to 11 synthetic overlapping peptides (phMOG) spanning the extracellular domain of human MOG by PBL from 9 MS patients and 15 control individuals (9 healthy controls and 6 patients with neurological diseases other than MS) further supports a prevalent role for the autoimmune response to MOG in MS, as only 1 of the 15 controls tested showed reactivity to any of the phMOG, whilst 5 out of the 9 patients studied reacted to at least 1 of the phMOG. PBL from 10 MS patients, and from 4 controls, were selected in vitro with each of the phMOG. Of the 10 patients studied 7 reacted to at least 1 phMOG upon secondary stimulation and the reactivity was mostly directed to epitopes localized within three main regions (amino acids 1–22, 34–56 and 64–96), as was observed for the primary response of PBL. The predominant response to MOG of PBL from MS patients as demonstrated in two separate studies using native MOG and rhMOG as antigens, and the high incidence of reactivity of these PBL compared to the lack of response to phMOG by control PBL, emphasize the relevance of MOG in MS pathogenesis and support a primary role for the autoimmune T cell response to MOG in disease development.
Myelin oligodendrocyte glycoprotein‐induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas‐ and Fas ligand‐deficient lpr and gld mice
Authors: Malipiero Ursula , Frei Karl , Spanaus Katharina‐Susanne , Agresti Cristina , Lassmann Hans , Hahne Michael , Tschopp Jürg , Eugster Hans‐Pietro , Fontana Adriano 
Published: March 2007

AbstractThe expression and action of Fas/Fas ligand (FasL) in multiple sclerosis has been postulated as a major pathway leading to inflammatory demyelination. To formally test this hypothesis, C57BL/6‐lpr and ‐gld mice, which due to gene mutation express Fas and FasL in an inactive form, were immunized with myelin oligodendrocyte glycoprotein peptide35–55. Whereas in wild‐type C57BL/6 mice, experimental autoimmune encephalomyelitis (EAE), was chronic/relapsing, EAE in lpr and gld mice was characterized by a lower incidence of disease and a monophasic course. This contrasts with C57BL/6 perforin knockout mice, which showed the most severe form of EAE of all mouse strains tested, the course being chronic relapsing. The difference noted cannot be attributed to an involvement of FasL in oligodendrocyte damage since oligodendrocytes are insensitive to FasL‐mediated cytotoxicity in vitro, and since in the acute phase of EAE gld mice also show CD4+T cell infiltrates with associated demyelination in brain and spinal cord. Unlike oligodendrocytes, astrocytes were killed by FasL in vitro. It remains to be established whether this latter finding explains the different disease course of lpr and gld mice compared to wild‐type and perforin knockout mice.
Cleavage of FLICE (caspase‐8) by granzyme B during cytotoxic T lymphocyte‐induced apoptosis
Authors: Medema Jan Paul , Toes René E. M. , Scaffidi Carsten , Zheng Timothy S. , Flavell Richard A. , Melief Cornelius J. M. , Peter Marcus E. , Offringa Rienk , Krammer Peter H. 
Published: March 2007

AbstractCytotoxic T lymphocytes induce apoptosis in target cells through the CD95(APO‐1/Fas) and the perforin/granzyme B (GrB) pathway. The exact substrate of GrB in vivo is still unknown, but to induce apoptosis GrB requires the activity of caspases in target cells. We show here that in HeLa target cells induction of apoptosis through the perforin/GrB pathway resulted in minor direct cleavage of CPP32 (caspase‐3) by GrB. Most caspase‐3 cleavage resulted from activation of an upstream caspase. Moreover, target cells derived from caspase‐3−/− mice displayed GrB‐induced poly(ADP‐ribose) polymerase (PARP) cleavage with only partially reduced efficiency compared to wild‐type target cells. This indicates that other PARP‐cleaving caspases can be activated during perforin/GrB‐induced cell death. In contrast to caspase‐3, FLICE (caspase‐8) was directly cleaved by GrB in HeLa cells. We therefore conclude that FLICE not only plays a central role in CD95(APO‐1/Fas)‐induced apoptosis but can also be directly activated during perforin/GrB‐induced apoptosis.
Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co‐localization of eotaxin mRNA to bronchial epithelial and endothelial cells
Authors: Ying Sun , Robinson Douglas S. , Meng Qiu , Rottman James , Kennedy Russ , Ringler Douglas J. , Mackay Charles R. , Daugherty Bruce L. , Springer Martin S. , Durham Stephen R. , Williams Timothy J. , Kay A. Barry 
Published: March 2007

AbstractEotaxin is a newly discovered C‐C chemokine which preferentially attracts and activates eosinophil leukocytes by acting specifically on its receptor CCR3. The airway inflammation characteristic of asthma is believed to be, at least in part, the result of eosinophil‐dependent tissue injury. This study was designed to determine whether there is increased expression of eotaxin and CCR3 in the bronchial mucosa of asthmatics and whether this is associated with disease severity. The major sources of eotaxin and CCR3 mRNA were determined by co‐localization experiments. Bronchial mucosal biopsy samples were obtained from atopic asthmatics and normal non‐atopic controls. Eotaxin and CCR3 mRNA were identified in tissue sections by in situ hybridization (ISH) using radiolabeled riboprobes and their protein product visualized by immunohistochemistry (IHC). Co‐localization experiments were performed by double ISH/IHC. Eotaxin and CCR3 (mRNA and protein) were significantly elevated in atopic asthmatics compared with normal controls. In the asthmatics there was a highly significant inverse correlation between eotaxin mRNA+ cells and the histamine provocative concentration causing a 20% fall in FEV1 (PC20). Cytokeratin‐positive epithelial cells and CD31+ endothelial cells were the major source of eotaxin mRNA whereas CCR3 co‐localized predominantly to eosinophils. These data are consistent with the hypothesis that damage to the bronchial mucosa in asthma involves secretion of eotaxin by epithelial and endothelial cells resulting in eosinophil infiltration mediated via CCR3. Since selective (eotaxin) and non‐selective C‐C chemokines such as RANTES, MCP‐3 and MCP‐4 all stimulate eosinophils via CCR3, this receptor is potentially a prime therapeutic target in the spectrum of diseases involving eosinophil‐mediated tissue damage.
Synthesis of Novel Covalently Linked Dimeric Phthalocyanines
Authors: Lyubimtsev Aleksey , Vagin Sergej , Syrbu Sergej , Hanack Michael 
Published: March 2007

AbstractWe report the syntheses of the dimeric homonuclear Pcs 9a and 9b and of the dimeric heteronuclear Pc 9c, starting from the unsymmetrical phthalocyanines 7a and 7b, each containing a phenolic OH group in one of its substituents. Compounds 9a and 9b were obtained by single‐step alkylations of 7a and 7b with 1,6‐dibromohexane or, in better yields, by coupling of Pcs 7a and 7b with the bromoalkyl‐derivatized Pcs 8a and 8b, while 9c was prepared by treatment of 8a with Pc‐Ni complex 7b. The dimeric Pcs 9a–9c show strong cofacial intramolecular association in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Ab initio conformational study of the P6 potential surface: Evidence for a low‐lying one‐electron‐bonded isomer
Authors: Hiberty Philippe C. , Volatron François 
Published: March 2007

AbstractThe low‐lying isomers of the P6 species are investigated at various levels of calculations, ranging from MP2/6‐31G(d) to CCSD(T) in triple‐zeta basis set involving polarization functions up to f. In addition to the five possible normal‐valent isomers, which obey the octet rules, several other conformations are found to be stationary points on the potential energy surface. Among the five normal‐valent isomers, the benzvalene structure is found to be the most stable one, in agreement with former studies. The benzene‐like D6h planar hexagon is the least stable one, lying 32.3 kcal/mol over benzvalene, and spontaneously distorts to a less symmetrical, nonplanar six‐membered ring. Above the benzvalene structure, and lying, respectively, 5.8 and 15.8 kcal/mol higher, the two lowest lying isomers are the prismane and the chair‐like forms. This latter conformation, which does not obey the octet rule, exhibits two one‐electron PP hemibonds and can be considered as a generic model for a new category of heterobenzene analogs, among which is the recently discovered dimer of diphosphirenyl radical. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:129–134, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20324
Biocorrosion investigation of two shape memory nickel based alloys: Ni‐Mn‐Ga and thin film NiTi
Authors: Stepan L.L. , Levi D.S. , Gans E. , Mohanchandra K.P. , Ujihara M. , Carman G.P. 
Published: March 2007

AbstractThin film nitinol and single crystal Ni‐Mn‐Ga represent two new shape memory materials with potential to be used as percutaneously placed implant devices. However, the biocompatibility of these materials has not been adequately assessed. Immersion tests were conducted on both thin film nitinol and single crystal Ni‐Mn‐Ga in Hank's balanced salt solution at 37°C and pH 7.4. After 12 h, large pits were found on the Ni‐Mn‐Ga samples while thin film nitinol displayed no signs of corrosion. Further electrochemical tests on thin film nitinol samples revealed breakdown potentials superior to a mechanically polished nitinol disc. These results suggest that passivation or electropolishing of thin film nitinol maybe unnecessary to promote corrosion resistance. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Discrimination of dynamical system models for biological and chemical processes
Authors: Lorenz Sönke , Diederichs Elmar , Telgmann Regina , Schütte Christof 
Published: March 2007

AbstractIn technical chemistry, systems biology and biotechnology, the construction of predictive models has become an essential step in process design and product optimization. Accurate modelling of the reactions requires detailed knowledge about the processes involved. However, when concerned with the development of new products and production techniques for example, this knowledge often is not available due to the lack of experimental data. Thus, when one has to work with a selection of proposed models, the main tasks of early development is to discriminate these models. In this article, a new statistical approach to model discrimination is described that ranks models wrt. the probability with which they reproduce the given data. The article introduces the new approach, discusses its statistical background, presents numerical techniques for its implementation and illustrates the application to examples from biokinetics. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007
There are exactly five biplanes with k = 11
Authors: Kaski Petteri , Östergård Patric R. J. 
Published: March 2007

AbstractA biplane is a 2‐(k(k − 1)/2 + 1,k,2) symmetric design. Only sixteen nontrivial biplanes are known: there are exactly nine biplanes with k < 11, at least five biplanes with k = 11, and at least two biplanes with k = 13. It is here shown by exhaustive computer search that the list of five known biplanes with k = 11 is complete. This result further implies that there exists no 3‐(57, 12, 2) design, no 11211 symmetric configuration, and no (324, 57, 0, 12) strongly regular graph. The five biplanes have 16 residual designs, which by the Hall–Connor theorem constitute a complete classification of the 2‐(45, 9, 2) designs. © 2007 Wiley Periodicals, Inc. J Combin Designs 16: 117–127, 2008
Experimental respiratory syncytial virus infection of four species of primates
Authors: Belshe Robert B. , Richardson Linda S. , London William T. , Sly D. Lewis , Lorfeld John H. , Camargo Ena , Prevar David A. , Chanock Robert M. 
Published: March 2007

AbstractFour species of nonhuman primates were inoculated intranasally with 103.1 to 103.7 plaque forming units (pfu) of respiratory syncytial (RS) virus. Adult squirrel monkeys and newborn rhesus monkeys became infected and shed small quantities (peak titer 102.0 pfu/ml of nasopharyngeal swab specimen) of virus, but illness did not develop. Infant cebus monkeys aged 2 months became infected, shed 102.3 to 103.8 pfu/ml of nasopharyngeal swab specimen, but did not become ill. Chimpanzees aged 15 to 18 months shed a large quantity of virus, up to 106.0 pfu/ml of nasopharyngeal swab specimen and developed an upper respiratory illness. Chimpanzees are proposed as a possible animal model for future study of the immunopathology of RS virus desease and for in vivo evaluation of attendated live virus vaccine candidates.
A case of coxsackie A9 virus infection with orchitis
Authors: Willems Wulf R. , Hornig Claus , Bauer Heinz , Klingmüller Volker 
Published: March 2007

AbstractA thirteen‐year‐old boy with bilateral orchitis was diagnosed as being infected by Coxsackie A9 virus by isolation of the virus from a throat swab and a fecal specimen. Serologic investigations revealed the development of transitory specific neutralizing IgM antibodies against the isolate and of persistent antibodies belonging to the other immunoglobulin classes. An etiology of the orchitis by any of the infectious agents usually found with this condition could be excluded.