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1.
B R Murphy J Harper D L Sly W T London N T Miller R G Webster 《Infection and immunity》1983,42(1):424-426
An influenza A virus isolated from seals [A/Seal/Mass/1/80 (H7N7)] and an isolate of this virus obtained from a human conjunctiva were evaluated for replication and virulence in squirrel monkeys. When the seal virus was administered intratracheally, it replicated in lungs and nasopharynges and induced illness almost to the same extent that a human influenza A virus [A/Udorn/72 (H3N2)] did. In one monkey that died of pneumonia, the seal virus was recovered from spleen, liver, and muscle as well as lung. After conjunctival administration in monkeys, the seal virus replicated to a peak titer in the conjunctivae 30-fold greater than that attained by the human virus, but this difference was not statistically significant. In contrast, the seal virus replicated less well than the human virus in the tracheae and nasopharynges when administered by the conjunctival route. These results indicate that the seal virus can replicate efficiently in primates, that it can spread systemically, and that it might differ from human virus in being able to replicate slightly better in primate conjunctival tissue. 相似文献
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A. Micozzi M. Nucci M. Venditti G. Gentile C. Girmenia G. Meloni P. Martino 《European journal of clinical microbiology & infectious diseases》1993,12(1):1-8
A prospective randomized trial was performed to compare the efficacy of a regimen containing a glycopeptide versus one containing a beta-lactamase inhibitor in the treatment of febrile episodes in neutropenic patients. Fifty-eight patients received piperacillin/amikacin/teicoplanin (group 1) and 56 received piperacillin/amikacin/tazobactam (group 2). In the case of persistence of fever without microbiological documentation of the cause, teicoplanin was also given empirically in group 2 on day 4, and amphotericin B in both groups on day 6. In 114 evaluable febrile episodes, the rate of success without modification of therapy was 60 % in patients on piperacillin/amikacin/teicoplanin and 41 % in patients on piperacillin/amikacin/tazobactam (p<0.03). Eleven of 34 patients in the latter group who failed to improve eventually responded upon addition of teicoplanin. Ten and nine patients in group 1 and group 2 respectively required the addition of amphotericin B for definite improvement. There were 14 episodes of gram-positive septicemia in each group: the response rate was 100 % in group 1 and 43 % in group 2. Three episodes of gram-negative breakthrough septicemia occurred in group 1 versus no cases in group 2 (p=0.1). Three deaths occurred in each group. Piperacillin/amikacin/tazobactam may be as efficacious as piperacillin/amikacin/teicoplanin in the treatment of febrile neutropenic patients provided the regimen is modified (usually by addition of teicoplanin) in unresponsive cases. 相似文献
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Visfatin是新发现的由内脏脂肪细胞分泌的一种脂肪细胞因子,可结合并激活胰岛素受体的非胰岛素结合部位,激活胰岛素受体信号通路,从而模拟胰岛素作用,降低机体血糖。这一因子还能够促进脂肪组织的分化、合成及积累。Visfatin cDNA序列与前B细胞克隆增强因子(PBEF)相同,Visfatin在细胞内尚发挥尼克酰胺磷酸核糖转移酶(Nampt)的作用,通过调节氧化型辅酶I(NAD)的生成从而调控Sirt1的活性,参与细胞的增殖、分化及调亡等过程。 相似文献
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The role of the Ek (E alpha kE beta k) molecule in the generation of suppressor T (Ts) cells specific for lactate dehydrogenase B (LDHB) was studied using different approaches. First, lymph node cells from LDHB-primed B10.A(2R) (AkEk) nonresponder mice were shown to suppress the LDHB-specific and Ak-restricted proliferative response of T cells from the congenic responder strain B10.A(4R), which does not express E molecules (AkEo). Similarly, lymph node cells from primed CBA (AkEk) mice suppressed the anti-LDHB response of Lyt-1+Lyt-2-T cells (depleted of Lyt-2-bearing Ts cells) from the same mice. Second, in vitro priming of 2R (AkEk) T cells with LDHB-pulsed 4R (AkEo) antigen-presenting cells (APC) generated T-cell proliferation but not suppression. Third, nonresponder 2R mice were turned into responders by injecting them with LDHB-pulsed 4R APC or monoclonal Ia.m7 antibody that blocks the Ek molecule. The data demonstrate that expression of Ek molecules by the APC is necessary to generate LDHB-specific Ts cells, which in turn prevent the proliferation of Lyt-1+Lyt-2- (probably helper) cells recognizing the same antigen in the context of the Ak molecule. 相似文献
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Su B Liu YH Pei RJ Yeh CC Yeh KT Lee KY Hsu YH Ho CC Lai YS 《Research communications in molecular pathology and pharmacology》1999,105(1-2):11-22
There are two sorted groups of cytokeratin 18 (CK18) in forms of assembly and disassembly in PLC/PRF/5 cells. A subcellular shifting is found in association with conditions of microtubule networks. The finding shows that CK18 mostly in forms of assembly, when microtubule networks are in status. The result also reveals that CK18 is relatively in forms of disassembly, while microtubule networks are disrupted in steps. It indicates that intact microtubule networks are probably a stabilizing factor of assembled CK18. It implies that CK18 is not a stable molecule when the cell is under environmental stress. 相似文献
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Maciej Banach Pawe Burchardt Krzysztof Chlebus Piotr Dobrowolski Dariusz Dudek Krzysztof Dyrbu Mariusz Gsior Piotr Jankowski Jacek J
wiak Longina Kosiewicz-Latoszek Irina Kowalska Maciej Maecki Aleksander Prejbisz Micha Rakowski Jacek Rysz Bogdan Solnica Dariusz Sitkiewicz Grayna Sygitowicz Grayna Sypniewska Tomasz Tomasik Adam Windak Dorota Zozuliska-Zikiewicz Barbara Cybulska 《Archives of Medical Science》2021,17(6):1447
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Control of arterial PCO2 by somatic afferents in sheep 总被引:2,自引:2,他引:0
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The phosphorylcholine (PC) determinant inStreptococcus pneumoniaeis known to be linked to the cell wall polysaccharides (C-Ps) and to the lipoteichoic acid (LTA) (Forssman antigen) of the plasma membrane. Western blotting with two PC specific murine monoclonal antibodies (MAbs) designated 145,F-2 (IgM) and 147,A-1 (IgA) showed a similar ladder-like pattern for all examined strains ofS. pneumoniaeandStreptococcus mitis. Purified antigens run in parallel indicated that this ladder pattern is due to the PC of LTA. Unlike other techniques, Western blotting thus enables the identification of only one of the streptococcal structures carrying the PC epitope. Gram-negative organisms were also examined, and six of 11Haemophilus influenzaestrains reacted with the MAbs. For this species, unlike the streptococci, only one fast moving band was detected. Analyses by thin-layer chromatography (TLC) detected the PC epitope in lipopolysaccharide (LPS) fraction fromH. influenzae. Some strains of theNeisseriaceaefamily were also positive by Western blotting, but TLC and immunostaining did not detect the PC determinant in LPS. 相似文献
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We examined changes in ionic and gating currents in CaV 1.2 channels when extracellular Ca2+ was reduced from 10 m m to 0.1 μ m . Saturating gating currents decreased by two-thirds ( K D ≈ 40 μ m ) and ionic currents increased 5-fold ( K D ≈ 0.5 μ m ) due to increasing Na+ conductance. A biphasic time dependence for the activation of ionic currents was observed at low [Ca2+ ], which appeared to reflect the rapid activation of channels that were not blocked by Ca2+ and a slower reversal of Ca2+ blockade of the remaining channels. Removal of Ca2+ following inactivation of Ca2+ currents showed that Na+ currents were not affected by Ca2+ -dependent inactivation. Ca2+ -dependent inactivation also induced a negative shift of the reversal potential for ionic currents suggesting that inactivation alters channel selectivity. Our findings suggest that activation of Ca2+ conductance and Ca2+ -dependent inactivation depend on extracellular Ca2+ and are linked to changes in selectivity. 相似文献
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Evaluation of avian-human reassortant influenza A/Washington/897/80 x A/Pintail/119/79 virus in monkeys and adult volunteers. 总被引:4,自引:2,他引:4
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M L Clements M H Snyder A J Buckler-White E L Tierney W T London B R Murphy 《Journal of clinical microbiology》1986,24(1):47-51
A reassortant influenza A virus was produced by mating an avian influenza A/Pintail/Alberta/119/79 (H4N6) virus with wild-type human influenza A/Washington/897/80 (H3N2) virus. The avian-human influenza A reassortant virus contained the genes coding for the hemagglutinin and neuraminidase surface antigens of the human influenza wild-type virus and the six other RNA segments (internal genes) of the avian influenza A virus donor. In the lower respiratory tract of squirrel monkeys, this avian-human influenza reassortant virus, like its avian influenza A parent virus, was restricted approximately 100-fold in replication compared with the wild-type human influenza A virus. Despite this restriction of replication, infection of monkeys with the avian-human influenza A reassortant virus induced resistance to wild-type human influenza A virus challenge. In comparison with the wild-type human influenza A virus, the avian-human influenza A reassortant was also fully attenuated when 10(5.5) to 10(7.5) 50% tissue culture infective doses were administered to susceptible adult volunteers. Attenuation was indicated by a more than 300-fold reduction in virus shedding and lack of reactogenicity. The reassortant virus did not spread to susceptible contacts and could not be isolated from the blood or stools of infected adults. The 50% human infectious dose was 10(6.2) 50% tissue culture infective dose, indicating that this reassortant virus is only slightly less infectious for adults than a similarly derived avian-human influenza A/Washington/80 X A/Mallard/78 reassortant virus. These findings suggest that the avian influenza A/Pintail/79 virus may be a satisfactory donor of attenuating genes for production of live, attenuated avian-human influenza A reassortant virus vaccines. 相似文献
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The influenza A components of live attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47), and virulent epidemic strains. The lesions responsible for attenuation within the six internal genes of each donor strain have been sequenced and described, but relatively little is known as to their stability before and after passage in susceptible hosts. In the work reported in this paper, RT-PCR restriction analysis and limited sequencing of individual genes were used to evaluate the stability of lesions in stocks of the both donor strains after passage in ferrets, which have been used widely as susceptible hosts for assessment of the virulence of influenza strains. Len/47 was shown to possess expected lesions by RT-PCR and restriction analysis. Substitution at position 1066 of the NP gene, which has been previously reported to be unique to Len/47 [Klimov et al., Virology 186 (1992) 795], was also shown to be present in all clones of Len/17. This change was confirmed by limited sequence analysis and was shown to be retained in progeny viruses isolated from the lungs and turbinates of inoculated ferrets. Two other changes in the PB2 and PB1 genes that were present in Len/47 were detected by limited sequence analysis alone. Further previously unreported minor changes were shown to be present for Len/17 and Len/47, but not both, and their significance is unknown. Limited replication of each donor strain occurred in ferrets and minimal clinical signs and histopathology were present. By contrast, the parental strain Len/57 and the recent epidemic strain A/Sydney/6/97 induced clinical signs and histopathology that were typical of influenza disease. 相似文献
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Analysis of PTCH/SMO/SHH pathway genes in medulloblastoma 总被引:7,自引:0,他引:7
Zurawel RH Allen C Chiappa S Cato W Biegel J Cogen P de Sauvage F Raffel C 《Genes, chromosomes & cancer》2000,27(1):44-51
Inactivation of the PTCH tumor suppressor gene occurs in a subset of sporadic medulloblastomas, suggesting that alterations in the PTCH pathway may be important in the development of this tumor. In order to address the frequency of genetic alterations affecting genes in this pathway, we used a combination of loss of heterozygosity (LOH) analysis, single-stranded conformational polymorphism (SSCP) analysis, and direct sequencing of DNA samples from sporadic primitive neuroectodermal tumors (PNETs). To identify alterations in the PTCH gene, we performed LOH analysis on 37 tumor DNA samples. Of those with matched constitutional DNA samples, one demonstrated LOH. Of those without matched constitutional DNA, six were homozygous with all markers. All exons of the PTCH gene were sequenced in these seven tumors, and three mutations were found. To identify alterations in the SHH and SMO genes, we analyzed all exons of both genes in 24 tumors with SSCP and sequenced any exons that showed aberrant band patterns. No mutations were found in either SHH or SMO in any tumor. We also identified the following genes as candidate tumor suppressors based on their roles in controlling hh/ptc signaling in Drosophila: EN-1 and EN-2, deletion of which results in a lack of cerebellar development in mice; SMAD family members 1-7, and protein kinase A subunits RIalpha, RIbeta, RIIbeta, Calpha, and Cbeta. Each of these genes was investigated in a panel of 24 matched constitutional and tumor DNA samples. Our search revealed no mutations in any of these genes. Thus, PTCH is the only gene in this complex pathway that is mutated with notable frequency in PNET. Genes Chromosomes Cancer 27:44-51, 2000. 相似文献
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Recent research on hematological malignancies has shown that malignant cells often co-opt physiological pathways to promote their growth and development. Bone marrow homeostasis requires a fine balance between cellular differentiation and self-renewal; cell survival and apoptosis; and cellular proliferation and senescence. The Ras/Raf/MEK/ERK pathway has been shown to be important in regulating these biological functions. Moreover, the Ras/Raf/MEK/ERK pathway has been estimated to be mutated in 30% of all cancers, thus making it the focus of many scientific studies which have lead to a deeper understanding of cancer development and help to elucidate potential weaknesses that can be targeted by pharmacological agents [1]. In this review, we specifically focus on the role of this pathway in physiological hematopoiesis and how augmentation of the pathway may lead to hematopoietic malignancies. We also discuss the challenges and success of targeting this pathway. 相似文献
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骨、软骨、椎间盘、肌腱等组织的自体细胞在体外培养、扩增困难,因此很难真正用于组织的缺损修复。干细胞具有自我更新和向多种组织定向诱导分化的特性,近年来干细胞研究的不断发展为其应用于矫形外科组织再生修复提供了可能。由于脂防来源问充质细胞(ASC)来源丰富、取材容易,近来备受研究者青睐,已被越来越多地应用于干细胞和组织工程领域。主要针对ASC在矫形外科骨,软骨/椎间盘/肌腱等组织修复中的应用作一综述。最近的ASC体内缺损修复结果为其应用于临床矫形外科组织修复的潜能提供了研究依据: 相似文献
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Salmonella typhimurium rpoS 《Microbial pathogenesis》1999,26(6):299-305
Salmonella typhimurium rpoS and rpoS aroA mutants are effective live vaccines in the murine model of salmonellosis (Coynault et al., Mol. Microbiol. 1996; 22: 149-60). Here, we further investigate the characteristics of these vaccines. The systemic humoral response induced by S. typhimurium rpoS, aroA and rpoS aroA vaccine candidates against S. typhimurium LPS was studied by ELISA. In BALB/c mice, the rpoS aroA strain induced a systemic anti-LPS humoral response similar to that induced by the rpoS and aroA strains. The virulence of aroA and rpoS aroA vaccines in nude (nu/nu) BALB/c mice was also compared. Salmonella typhimurium aroA and rpoS aroA vaccines both produced slowly progressing lethal infections in athymic mice inoculated i.p. but the rpoS aroA strain was more attenuated than the aroA strain, as determined by time to death and bacterial counts in spleens. Finally, a rpoS mutant of Salmonella dublin conferred protection in mice against an oral challenge with a wild-type strain of S. dublin whereas a rpoS mutant of S. typhimurium did not. This suggests that the protection provided by the S. typhimurium rpoS vaccine is serotype-dependent. 相似文献
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Cold-Adapted Variants of Influenza A Virus: Evaluation in Adult Seronegative Volunteers of A/Scotland/840/74 and A/Victoria/3/75 Cold-Adapted Recombinants Derived from the Cold-Adapted A/Ann Arbor/6/60 Strain 总被引:2,自引:0,他引:2
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Brian R. Murphy H. Preston Holley Jr. Erick J. Berquist Myron M. Levine Susan B. Spring Hunien F. Maassab Alan P. Kendal Robert M. Chanock 《Infection and immunity》1979,23(2):253-259
Influenza A/Scotland/74 (H3N2) and A/Victoria/75 (H3N2) cold-adapted (ca) recombinant viruses, prepared by mating the A/Ann Arbor/6/60 (H2N2) ca donor virus and influenza A wild-type virus, were evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, =1:8) for level of attenuation, antigenicity, and genetic stability of the temperature-sensitive and ca phenotypes. At 10(7.0) to 10(7.5) 50% tissue culture infective doses the A/Scotland/74 and A/Victoria/75 ca recombinant viruses were clearly attenuated and antigenic. However, one of eight vaccinees infected with 10(7.5) 50% tissue culture infective doses of the A/Scotland/74 ca recombinant had a febrile reaction (39 degrees C). At a 10-fold higher dose (10(8.5) 50% tissue culture infective doses), 4 of 12 A/Scotland/74 vaccinees had a febrile and/or systemic reaction. Febrile reactions were not observed in volunteers who received the A/Victoria/75 ca recombinant virus, whereas 3 of the 12 vaccinees had mild upper respiratory tract symptoms, in one instance associated with mild systemic manifestations. Significantly, the serum hemagglutination- and neuraminidase-inhibiting antibody responses were comparable to those induced by wild-type virus. Both ca recombinant viruses were shed in low titer for a short period of time. Each isolate retained the temperature-sensitive phenotype. However, there was evidence of genetic instability of the ca marker in that 7 of 24 isolates exhibited some loss of the ca property, and one isolate completely lost the capacity to produce plaques at 25 degrees C. The retention of a low level of residual reactogenicity in the A/Scotland/74 ca recombinant suggests that acquisition of the ca and temperature-sensitive phenotypes by a ca recombinant virus may not always bring about a satisfactory level of attenuation for individuals lacking hemagglutinin immunity. 相似文献