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11.
Hessell AJ Hangartner L Hunter M Havenith CE Beurskens FJ Bakker JM Lanigan CM Landucci G Forthal DN Parren PW Marx PA Burton DR 《Nature》2007,449(7158):101-104
Most successful vaccines elicit neutralizing antibodies and this property is a high priority when developing an HIV vaccine. Indeed, passively administered neutralizing antibodies have been shown to protect against HIV challenge in some of the best available animal models. For example, antibodies given intravenously can protect macaques against intravenous or mucosal SHIV (an HIV/SIV chimaera) challenge and topically applied antibodies can protect macaques against vaginal SHIV challenge. However, the mechanism(s) by which neutralizing antibodies afford protection against HIV is not understood and, in particular, the role of antibody Fc-mediated effector functions is unclear. Here we report that there is a dramatic decrease in the ability of a broadly neutralizing antibody to protect macaques against SHIV challenge when Fc receptor and complement-binding activities are engineered out of the antibody. No loss of antibody protective activity is associated with the elimination of complement binding alone. Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complexed infected cells is important in reducing virus yield from infected cells. Overall, the data suggest the potential importance of activity against both infected cells and free virus for effective protection against HIV. 相似文献
12.
We studied rapid changes in location of cyclic GMP in Tetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5-1 min). Later (1-5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes. 相似文献
13.
Carpten JD Robbins CM Villablanca A Forsberg L Presciuttini S Bailey-Wilson J Simonds WF Gillanders EM Kennedy AM Chen JD Agarwal SK Sood R Jones MP Moses TY Haven C Petillo D Leotlela PD Harding B Cameron D Pannett AA Höög A Heath H James-Newton LA Robinson B Zarbo RJ Cavaco BM Wassif W Perrier ND Rosen IB Kristoffersson U Turnpenny PD Farnebo LO Besser GM Jackson CE Morreau H Trent JM Thakker RV Marx SJ Teh BT Larsson C Hobbs MR 《Nature genetics》2002,32(4):676-680
We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors. 相似文献
14.
L. Kohidai J. Barsony J. Roth S. J. Marx 《Cellular and molecular life sciences : CMLS》1992,48(5):476-481
We studied rapid changes in location of cyclic GMP inTetrahymena pyriformis. Insulin caused cGMP localization in cilia and near the plasma membrane (0.5–1 min). Later (1–5 min) cGMP localization was diffuse in cytoplasm with perinuclear accentuation. Inactive insulin analogs did not elicit these changes. 相似文献
15.
Zusammenfassung
Alt-rezessive Erbsenpflanzen zeigen als Keimlinge normale Pigmentbildung, werden aber oberhalb des 5. oder 6. Knotens chlorotisch und sterben vor der Samenreife ab. Aufpfropfen des Wildtyps und Zugabe eines Extraktes regenerieren die Pigmentbildung in der Mutante, was auf die Anwesenheit einer übertragbaren, stark basischen Substanz schliessen lässt.
Approved by the Director of the New York Strate Agricultural Experiment Station, Geneva, New York, for publication as Journal paper No 1916.
The authors gratefully acknowledge the technical assistance of Mrs.Betty Chase, John F. Kenny andThomas G. Copeland. 相似文献
Approved by the Director of the New York Strate Agricultural Experiment Station, Geneva, New York, for publication as Journal paper No 1916.
The authors gratefully acknowledge the technical assistance of Mrs.Betty Chase, John F. Kenny andThomas G. Copeland. 相似文献
16.
Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes
Nikolaus Marx Mathias Burgmaier Philipp Heinz Mirjam Ostertag Angelina Hausauer Helga Bach Renate Durst Vinzenz Hombach Daniel Walcher 《Cellular and molecular life sciences : CMLS》2010,67(20):3549-3555
The present study examined the effect of GLP-1(1-37) on chemokine-induced CD4-positive lymphocyte migration as an early and
critical step in atherogenesis. Pretreatment with GLP-1(1-37) reduced the SDF-induced migration of isolated human CD4-positive
lymphocytes in a concentration-dependent manner. Similar effects were seen when RANTES was used as a chemokine. GLP-1(1-37)’s
effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity.
Downstream, GLP-1(1-37) inhibited SDF-induced phosphorylation of MLC and cofilin and limited f-actin formation as well as
ICAM3 translocation. Furthermore, exendin-4 inhibited SDF-induced migration of CD4-positive lymphocytes similarly to GLP-1(1-37),
and transfection of these cells with GLP-1 receptor siRNA abolished GLP-1(1-37)’s action on chemokine-induced ICAM3 translocation,
suggesting an effect mediated via the GLP-1 receptor. Thus, GLP-1(1-37) inhibits chemokine-induced CD4-positive lymphocyte
migration by inhibition of the PI3-kinase pathway and via the GLP-1 receptor. This effect provides a potential novel mechanism
for how GLP-1(1-37) may modulate vascular disease. 相似文献
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18.
Veazey RS Klasse PJ Schader SM Hu Q Ketas TJ Lu M Marx PA Dufour J Colonno RJ Shattock RJ Springer MS Moore JP 《Nature》2005,438(7064):99-102
Human immunodeficiency virus type 1 (HIV-1) continues to spread, principally by heterosexual sex, but no vaccine is available. Hence, alternative prevention methods are needed to supplement educational and behavioural-modification programmes. One such approach is a vaginal microbicide: the application of inhibitory compounds before intercourse. Here, we have evaluated the microbicide concept using the rhesus macaque 'high dose' vaginal transmission model with a CCR5-receptor-using simian-human immunodeficiency virus (SHIV-162P3) and three compounds that inhibit different stages of the virus-cell attachment and entry process. These compounds are BMS-378806, a small molecule that binds the viral gp120 glycoprotein and prevents its attachment to the CD4 and CCR5 receptors, CMPD167, a small molecule that binds to CCR5 to inhibit gp120 association, and C52L, a bacterially expressed peptide inhibitor of gp41-mediated fusion. In vitro, all three compounds inhibit infection of T cells and cervical tissue explants, and C52L acts synergistically with CMPD167 or BMS-378806 to inhibit infection of cell lines. In vivo, significant protection was achieved using each compound alone and in combinations. CMPD167 and BMS-378806 were protective even when applied 6 h before challenge. 相似文献