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81.
Jin-Kyoo Kim May-Fang Tsen Victor Ghetie E. Sally Ward 《European journal of immunology》1994,24(3):542-548
Site-directed mutagenesis has been used to change amino acid residues of a recombinant Fc-hinge fragment derived from the murine immunoglobulin (Ig)G1 molecule, and the effects of these mutations on the pharmacokinetics of the Fc-hinge fragment have been determined. Specifically, Ile-253, His-310 and Gln-311 of the CH2 domain and His-433 and Asn-434 of the CH3 domain have been changed. In the three dimensional structure of an antibody, these amino acids are in close proximity to each other at the CH2-CH3 domain interface. The mutated Fc-hinge fragments have been purified from recombinant Escherichia coli cells and their pharmacokinetic parameters determined in mice and compared with those of the wild-type Fc-hinge fragment. The results show that the site of the IgG1 molecule that controls the catabolic rate (the ‘catabolic site’) is located at the CH2-CH3 domain interface and overlaps with the Staphylococcal protein A binding site. 相似文献
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83.
Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals. 相似文献
84.
Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure 总被引:2,自引:0,他引:2
Staninec M Marshall GW Hilton JF Pashley DH Gansky SA Marshall SJ Kinney JH 《Journal of biomedical materials research》2002,63(3):342-345
Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure. 相似文献
85.
Floyd Thompson Julia Emerson William Dalton Jin-Ming Yang Daniel McGee Hugo Villar Sally Knox Kathy Massey Ronald Weinstein Achyut Bhattacharyya Jeffrey Trent 《Genes, chromosomes & cancer》1993,7(4):185-193
Cytogenetic analysis was performed on a selected series of short-term cultures of primary breast carcinomas from 28 patients. All patients had histopathologically confirmed malignancies, with the majority (25/28 cases) demonstrating infiltrating ductal carcinoma. All 28 cases evidenced clonal chromosome abnormalities, with 10/28 displaying only numeric aberrations, whereas 18/28 displayed clonal structural alterations. In near-diploid tumors the most common numeric changes were — 17 and — 19. However, trisomy 7 was the only numeric change in two near-diploid tumors. Structural chromosome alterations were primarily isochromosomes, apparent terminal deletions, and unbalanced non-reciprocal translocations. Chromosomes 1 (10/18–56%) and 6 (8/18–44%) were most frequently altered in this series. Breakpoints of clonal structural abnormalities were shown to cluster to several chromosome segments, including 1p22-q11, 3p11, 6p11–13, 7p11-q11, 8p11-q11, and 19q13. Analysis of the gain or loss of specific chromosome segments revealed that the most consistent tendency was over-representation of 1q, 3q, and 6p. © 1993 Wiley-Liss, Inc. 相似文献
86.
Lisa A. Taneyhill Sally A. Moody Timothy Cox Ophir D. Klein Ralph Marcucio Richard A. Schneider Paul A. Trainor 《American journal of medical genetics. Part A》2019,179(5):864-869
The mission of the Society for Craniofacial Genetics and Developmental Biology (SCGDB) is to promote education, research, and communication about normal and abnormal development of the tissues and organs of the head. The SCGDB welcomes as members undergraduate students, graduate students, postdoctoral researchers, medical and dental practitioners, scientists, and academicians who possess an interest in craniofacial biology. Each year our members come together to share their novel findings, build upon, and challenge current knowledge of craniofacial biology. 相似文献
87.
Ouadrhiri Y Pilette C Monteiro RC Vaerman JP Sibille Y 《American journal of respiratory cell and molecular biology》2002,26(3):315-332
Human alveolar macrophages (HAM) express FcalphaR receptors for immunoglobulin (Ig)A which could link humoral and cellular branches of lung immunity. Here, we investigate the effects of polymeric (p-IgA) and secretory (S-IgA) IgA interaction with Fc(alpha)R on lipopolysaccharide (LPS)- and phorbol myristate acetate (PMA)-activated respiratory burst and TNF-alpha release by HAM. Activation of HAM with LPS and PMA increases the respiratory burst and TNF-alpha release through activation of the extracellular signal-related protein kinases 1 and 2 (ERK1/2) pathway, because these effects are inhibited by treatment of HAM with PD98059, a selective inhibitor of mitogen-activated protein (MAP)/ERK kinases (MEK) pathway. S-IgA and p-IgA downregulate the LPS-increased respiratory burst in HAM through an inhibition of ERK1/2 activity. In contrast, p- and S-IgA induce an increase in the respiratory burst of PMA-treated HAM. This effect is associated with an upregulation by IgA of the PMA-induced phosphorylation of ERK1/2 and is also inhibited by PD98059. Moreover, p-IgA and S-IgA enhance TNF-alpha release by HAM through an alternative pathway distinct from ERK1/2. Because LPS is known to activate nuclear factor-kappaB (NF-kappaB) in HAM, we evaluate the effect of IgA on NF-kappaB. Treatment of HAM with LPS, p- and S-IgA, but not PMA, induces NF-kappaB activation through IkappaBalpha phosphorylation and subsequent proteolysis. Antioxidants, namely N-acetylcysteine (NAC) and glutathione (GSH), have no effects on IgA-mediated NF-kappaB nuclear translocation and only a minor and late effect on that of LPS, suggesting that reactive oxygen intermediates (ROI) play a minor role in HAM activation through NF-kappaB. TNF-alpha release by LPS-activated HAM is sensitive to NF-kappaB inhibition and only partly to oxidant scavenging. In contrast, TNF-alpha release by IgA-treated HAM is not dependent on oxidants and only partly dependent on NF-kappaB. Our results show a differential HAM regulation by IgA through both dependent and independent modulation of ERK pathway. In addition, IgA activates NF-kappaB and this effect was independent on oxidants. These data may help to understand the role of IgA in both lung protection and inflammation. 相似文献
88.
Blower S 《Herpes : the journal of the IHMF》2004,11(Z3):138A-146A
Mathematical models are useful tools for summarizing and testing current knowledge about a system and predicting trends. Models have shown that medical and behavioural changes can substantially affect herpes simplex virus type 2 (HSV-2) transmission and can be used to develop rational epidemic control policies. The spread of the genital herpes epidemic and the potential impact of HSV antiviral treatment in the immunocompetent population have been addressed by four models. HSV drug resistance to antiviral drugs is predicted to be minimal. Assuming that drug-resistant mutants are attenuated both in infectivity and reactivity, one model predicted that even after 25 years, only 5 in 10,000 individuals will shed drug-resistant virus, even if rates of usage of antivirals are high. The models show that increased usage of episodic antiviral therapy will be beneficial in reducing the herpes epidemic. Results also show that the transmission rate can be reduced by preventing infection (safer sex), reduced time spent in non-monogamous relationships or the advent of effective therapeutic HSV vaccines. One model has indicated that suppressive therapy will have only a minimal impact on HSV prevalence; however, the results of this modelling study are limited as it assumed that suppressive therapy would only be given to incident infections. More recent research using a model based upon virological core groups (and treating both incident and prevalent infections) shows that suppressive therapy could cause a substantial reduction in HSV-2 incidence rates. Current modelling is also focused on modelling how HSV-2 antiviral treatment will impact the HIV epidemic. 相似文献
89.
90.
1. Responses of neurons in the auditory cortex of the albino rat were examined using microelectrode mapping techniques. Characteristic frequencies were determined for numerous electrode penetrations across the cortical surface in individual animals. A primary auditory area was identified in the posterolateral neocortex that was characterized by short latency responses to tone bursts and tonotopic organization with high frequencies represented rostrally and low frequencies, caudally. Within this area cells with similar characteristic frequencies were aligned in a dorsoventral orientation to form isofrequency contours. 2. Tuning curves obtained from primary auditory cortex were characteristically "V" shaped with Q10's ranging from 0.97 to 28.4. Maximum Q10 values increased monotonically with characteristic frequency (CF). The lowest thresholds at CF closely approximated the behavioral audiogram for the albino rat. Many neurons, however, had CF thresholds well above the behavioral limit. 3. Areas were found dorsal and ventral to the primary auditory cortex in which CF's were clearly discontinuous with the neighboring isofrequency contours. These data suggest the presence of other auditory fields, the detailed characteristics of which have yet to be examined. 相似文献