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991.
Ines Santisteban Francisco X. Arredondo-Vega Susan Kelly Marianne Debre Alain Fischer Jean Louis Prignon Bettina Hilman Jane Eldahr David H. Dreyfus Erwin W. Gelfand P. Lynne Howell Michael S. Hershfield 《Human mutation》1995,5(3):243-250
Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + 1G→A) in the 5′ splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency disease, the most common phenotype associated with ADA deficiency. When expressed in vitro, the H15D, A83D, and A179D proteins lacked detectable ADA activity. The splicing defect caused skipping of exon 5, resulting in premature termination of translation and a reduced level of mRNA. H15D is the first naturally occurring mutation of a residue that coordinates directly with the enzyme-associated zinc ion. Molecular modeling based on the atomic coordinates of murine ADA suggests that the D15 mutation would create a cavity or gap between the zinc ion and the side chain carboxylate of D15. This could alter the ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism. A83 and A179 are not directly involved in the active site, but are conserved residues located respectively in a helix 4 and β strand 4 of the α/β barrel. Replacement of these small hydrophobic Ala residues with the charged, more bulky Asp side chain may distort ADA structure and affect enzyme stability or folding.© 1995 wiley-Liss, Inc. 相似文献
992.
Jasmin Shen Robert Brackett Thomas Fischer Alan Holder Frank Kellogg J. Gabriel Michael 《Infection and immunity》1981,32(2):967-968
Immunoglobulin E antibodies to Psuedomonas aeruginosa were demonstrated in patients with cystic fibrosis colonized with the bacterium. 相似文献
993.
Eduard I Dedkov Mathew T Thomas Milan Sonka Fuxing Yang Thomas W Chittenden John M Rhodes Michael Simons Erik L Ritman Robert J Tomanek 《Developmental dynamics》2007,236(7):2004-2010
Syndecan-4 and its cytoplasmic binding partner, synectin, are known to play a role in FGF-2 signaling and vascular growth. To determine their roles in coronary artery/arteriolar formation and growth, we compared syndecan-4 and synectin null mice with their wild-type counterparts. Image analysis of arterioles visualized by smooth muscle alpha-actin immunostaining revealed that synectin (-/-) mice had lower arteriolar length and volume densities than wild-type mice. As shown by electron microscopic analysis, arterioles from the two did not differ in morphology, including their endothelial cell junctions, and the organization and distribution of smooth muscle. Using micro-computer tomography, we found that the size and branching patterns of coronary arteries (diameters > 50 microm) were similar for the two groups, a finding that indicates that the growth of arteries is not influenced by a loss of synectin. Syndecan-4 null male mice also had lower arteriolar length densities than their gender wild-type controls. However, female syndecan-4 null mice were characterized by higher arteriolar length and volume densities than their gender-matched wild-type controls. Thus, we conclude that both synectin and syndecan-4 play a role in arteriolar development, a finding that is consistent with previous evidence that FGF-2 plays a role in coronary arterial growth. Moreover, our data reveal that gender influences the arteriolar growth response to syndecan-4 but not to synectin. 相似文献
994.
Michael P. Cancro 《Immunological reviews》2004,197(1):89-101
Summary: B cells complete maturation after migrating to the periphery, where they transit several intermediate developmental stages prior to recruitment into the long-lived primary pool. Because B-lineage commitment is not regulated by peripheral pool size and most peripheral B cells are quiescent, the primary factors governing steady-state numbers are the proportion of immature B cells surviving transit through later developmental stages and the longevity of mature B cells themselves. Substantial evidence indicates that the B-cell receptor (BCR) plays an essential role in all these processes, but recent findings suggest a central role for the recently described tumor necrosis factor (TNF) family member, B-lymphocyte stimulator (BLyS). Signaling through one of the BLyS receptors, BLyS receptor 3 (BR3), controls B-cell numbers in two ways: by varying the proportion of cells that complete transitional B-cell development and by serving as the primary determinant of mature B-cell longevity. The recent discovery that BCR signaling is selectively coupled to BR3 expression in a developmentally regulated fashion links BCR- and BLyS-mediated events, suggesting that specificity-based selection and survival may be mechanistically similar processes. 相似文献
995.
James D. Ogle J. Greg Noel Ambikaipakan Balasurbramaniam R. Michael Sramkoski Cora K. Ogle J. Wesley Alexander 《Inflammation》1990,14(2):185-194
Both recombinant IL-1 and - caused an upregulation of C3b receptors (CR1) on human neutrophils and caused a receptor-mediated enhancement of phagocytosis of C3b·IgG-coated microspheres by these leukocytes. The and forms of the recombinant cytokine were of comparable potency regarding CR1 upregulation, although both generally had less than 25% of the potency of FMLP in this respect. Recombinant IL-1 was slightly more potent than the form of the cytokine regarding phagocytosis of opsonized microspheres and, again, both forms were less potent than FMLP in causing an enhancement of phagocytosis by neutrophils. The synthetic noninflammatory immunostimulatory nonapeptide corresponding to residues 163–171 of IL-1 was completely inert with respect to upregulation of CR1 on neutrophils and the enhancement of phagocytosis by these cells. Thus this domain in the intact IL-1 molecule apparently is not involved in CR1 upregulation and the ensuing enhancement in phagocytosis by neutrophils, although it is apparently important in the immunostimulatory activity regarding the proliferation of lymphocytes. 相似文献
996.
Depressed patients show a reduction of natural killer (NK) cell activity which may be associated with specific depressive symptoms. The present study demonstrated that sleep disturbance and retardation, but not other depressive symptoms, were negatively correlated with NK activity in 38 depressed patients. Specific behavioral changes in depression such as sleep disturbance and retardation were found to predict 16% of the variance of cytotoxicity levels in depression. 相似文献
997.
Loughrey MB Mitchell C Mann GB Michael M Waring PM 《Journal of clinical pathology》2005,58(7):779-781
This report describes a case of unresectable primary gastrointestinal stromal tumour (GIST) treated with imatinib on a neoadjuvant basis, before subsequent successful surgical resection. After six months of imatinib, computed tomography and positron emission tomography imaging demonstrated a significant size reduction and complete metabolic response to treatment, rendering the tumour resectable. Mutational analysis showed an activating KIT mutation in exon 11. The pathological appearance of the resected tumour was heterogeneous with extensive necrosis, cystic and myxoid change, extensive hypocellularity, and patchy foci of residual viable tumour. The implications for this management option of radiological, pathological, and molecular assessment are discussed. 相似文献
998.
Influence of different hormonal regimens on endometrial microvascular density and VEGF expression in women suffering from breakthrough bleeding 总被引:1,自引:0,他引:1
Rogers PA Martinez F Girling JE Lederman F Cann L Farrell E Tresserra F Patel N 《Human reproduction (Oxford, England)》2005,20(12):3341-3347
BACKGROUND: The aim of this study was to quantify blood vessel density (BVD) and immunoreactive vascular endothelial growth factor (VEGF) levels in endometrial biopsies taken from women suffering breakthrough bleeding (BTB) under different exogenous hormonal regimes. METHODS: Endometrial biopsies from women in Melbourne with BTB were divided into four groups: combined-continuous hormone therapy (HT) (estrogen and progestin taken daily), cyclical HT (daily estrogen with progestin for 14 days each cycle), progestin-only, or no HT. Subjects from Barcelona were using the Mirena intrauterine levonorgestrel-releasing system for contraceptive purposes, with menstrual diaries for classification into four groups (amenorrhea, infrequent, regular and prolonged). Control biopsies from Melbourne were included in the study. Endometrial samples were immunostained for VEGF and blood vessel localization using an antibody to CD34. RESULTS: Results showed that BVD was significantly reduced in the progestin-only treated group compared with the other three treatment groups (P = 0.028). In addition, all four Mirena BTB groups had significantly reduced BVD compared with controls. Considerable heterogeneity was observed in VEGF immunostaining within and between individual samples with no major differences between HT or Mirena. CONCLUSION: These results provide strong evidence that unopposed progestins reduce endometrial BVD and that there is no link between VEGF immunostaining and BVD or BTB. 相似文献
999.
1000.
Tanja Vogel Holly Boettger-Tong Indrajit Nanda Frank Dechend Alexander I. Agulnik Colin E. Bishop Michael Schmid Jorg Schmidtke 《Chromosome research》1998,6(1):35-40
Sequences homologous to human and bovine TSPY were isolated from M. musculus testicular cDNA, and a nearly full-length gene was polymerase chain reaction (PCR) amplified from mouse genomic DNA. This gene is apparently non-functional. Contrary to the situation encountered in species along the primate and artiodactyl lineages, in which TSPY is moderately repetitive, murine Tspy appears to be single copy. Murine Tspy is located on Yp, i.e. in the same syntenic group as in man. Sequence comparisons of murine, human and bovine TSPY exons suggest that TSPY became non-functional during rodent evolution. 相似文献