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排序方式: 共有123条查询结果,搜索用时 15 毫秒
1.
Characterization of a membrane-associated protein kinase of multidrug-resistant HL60 cells which phosphorylates P-glycoprotein 总被引:1,自引:0,他引:1
Cells containing increased levels of the membrane phosphoprotein P-glycoprotein exhibit a multidrug-resistant phenotype. In the present study we have analyzed protein kinases capable of phosphorylating P-glycoprotein in membranes of HL60 cells isolated for resistance to vincristine. Analysis of this system demonstrates that in isolated membranes the protein kinase inhibitor staurosporine greatly reduces P-glycoprotein phosphorylation. In contrast, the kinase inhibitor H-7 does not affect this reaction. Fractionation of solubilized membrane proteins from sensitive and resistant cells on DEAE-cellulose reveals a major protein kinase (PK-1) which exhibits optimal activity in the presence of Mn2+ and histone H1. This enzyme fraction does not contain detectable levels of protein kinase C or cAMP-dependent protein kinase. PK-1 phosphorylation of two endogenous proteins is, however, greatly enhanced in the presence of phosphatidylserine or phosphatidyl-inositol. In reaction mixtures containing Mg2+ or Mn2+ in the absence of phospholipid, PK-1 from resistant cells phosphorylates an endogenous protein of 180 kilodaltons (P180), which exhibits an electrophoretic mobility identical to P-glycoprotein. In parallel experiments with PK-1 from sensitive cells there is no detectable phosphorylation of a P180 protein. P180 phosphorylated by PK-1 from resistant cells is immunoprecipitated by antibody against P-glycoprotein. Additional studies demonstrate that PK-1 is capable of phosphorylating specific synthetic peptides which correspond to the sequence of P-glycoprotein. Peptide phosphorylation occurs at both serine and threonine residues. These studies thus identify a novel membrane-associated protein kinase in HL60 cells which is capable of phosphorylating P-glycoprotein. This enzyme may have an important role in regulating levels of multidrug resistance. 相似文献
2.
Genevieve G. A. Fouda Joshua D. Amos Andrew B. Wilks Justin Pollara Caroline A. Ray Anjali Chand Erika L. Kunz Brooke E. Liebl Kaylan Whitaker Angela Carville Shannon Smith Lisa Colvin David J. Pickup Herman F. Staats Glenn Overman Krissey Eutsey-Lloyd Robert Parks Haiyan Chen Celia LaBranche Susan Barnett Georgia D. Tomaras Guido Ferrari David C. Montefiori Hua-Xin Liao Norman L. Letvin Barton F. Haynes Sallie R. Permar 《Journal of virology》2013,87(12):6986-6999
We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector (n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 (P = 0.03) and CAP45 (P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk (P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission. 相似文献
3.
4.
A serologic survey was conducted on an American bison (Bison bison) herd in Kansas for antibodies against Brucella spp., Leptospira interrogans serovar canicola, pomona, grippotyphosa, icterohaemorrhagiae, and hardjo, Anaplasma spp., bluetongue virus, infectious bovine rhinotracheitis virus and bovine viral diarrhea virus. There was an increase in prevalence of bluetongue antibodies from 38% in 1987 to 100% in 1989 in animals greater than or equal to 24-mo-old. Prevalences of antibodies against the other livestock pathogens were either negative or at levels associated with previous vaccination. 相似文献
5.
Claudia T Guimaraes Christiano C Simoes Maria Marta Pastina Lyza G Maron Jurandir V Magalhaes Renato CC Vasconcellos Lauro JM Guimaraes Ubiraci GP Lana Carlos FS Tinoco Roberto W Noda Silvia N Jardim-Belicuas Leon V Kochian Vera MC Alves Sidney N Parentoni 《BMC genomics》2014,15(1)
Background
Aluminum (Al) toxicity is an important limitation to food security in tropical and subtropical regions. High Al saturation on acid soils limits root development, reducing water and nutrient uptake. In addition to naturally occurring acid soils, agricultural practices may decrease soil pH, leading to yield losses due to Al toxicity. Elucidating the genetic and molecular mechanisms underlying maize Al tolerance is expected to accelerate the development of Al-tolerant cultivars.Results
Five genomic regions were significantly associated with Al tolerance, using 54,455 SNP markers in a recombinant inbred line population derived from Cateto Al237. Candidate genes co-localized with Al tolerance QTLs were further investigated. Near-isogenic lines (NILs) developed for ZmMATE2 were as Al-sensitive as the recurrent line, indicating that this candidate gene was not responsible for the Al tolerance QTL on chromosome 5, qALT5. However, ZmNrat1, a maize homolog to OsNrat1, which encodes an Al3+ specific transporter previously implicated in rice Al tolerance, was mapped at ~40 Mbp from qALT5. We demonstrate for the first time that ZmNrat1 is preferentially expressed in maize root tips and is up-regulated by Al, similarly to OsNrat1 in rice, suggesting a role of this gene in maize Al tolerance. The strongest-effect QTL was mapped on chromosome 6 (qALT6), within a 0.5 Mbp region where three copies of the Al tolerance gene, ZmMATE1, were found in tandem configuration. qALT6 was shown to increase Al tolerance in maize; the qALT6-NILs carrying three copies of ZmMATE1 exhibited a two-fold increase in Al tolerance, and higher expression of ZmMATE1 compared to the Al sensitive recurrent parent. Interestingly, a new source of Al tolerance via ZmMATE1 was identified in a Brazilian elite line that showed high expression of ZmMATE1 but carries a single copy of ZmMATE1.Conclusions
High ZmMATE1 expression, controlled either by three copies of the target gene or by an unknown molecular mechanism, is responsible for Al tolerance mediated by qALT6. As Al tolerant alleles at qALT6 are rare in maize, marker-assisted introgression of this QTL is an important strategy to improve maize adaptation to acid soils worldwide.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-153) contains supplementary material, which is available to authorized users. 相似文献6.
Rose E Staats R Thissen U Otten JE Schmelzeisen R Jonas I 《Plastic and reconstructive surgery》2002,110(2):392-396
Sleep-disordered breathing is frequently associated with children presenting congenital midface defects. Because of structural and functional anomalies in the upper airway, children with cleft palate, especially after surgery, may carry a higher risk of developing sleep-disordered breathing. However, the presence of such sleep-disordered breathing in older cleft palate children has not been emphasized. The aim of this comparative overnight cardiorespiratory sleep study was to evaluate cleft palate patients according to sleep-disordered breathing. A group of 43 cleft palate children (17 girls and 26 boys; mean age, 12.1 +/- 3.8 years) was compared with a control group of 20 randomly selected, noncleft children matched for age, sex, and body mass index. None of the patients suffered from manifest sleep-disordered breathing. Cleft palate patients had a statistically significantly higher respiratory disturbance index and snoring index, but no increased apnea index. The data suggest that cleft palate patients having undergone primary closure of the palate demonstrate microsymptoms of nocturnal upper airway obstruction. 相似文献
7.
Anna CC Aguiar Ananda C Cunha Isabela Penna Ceravolo Regina A Correia Gon?alves Arildo JB Oliveira Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2015,110(7):906-913
Several species of Aspidosperma plants are used to treat diseases in
the tropics, including Aspidosperma ramiflorum, which acts against
leishmaniasis, an activity that is experimentally confirmed. The species, known as
guatambu-yellow, yellow peroba,
coffee-peroba andmatiambu, grows in the Atlantic
Forest of Brazil in the South to the Southeast regions. Through a guided
biofractionation of A. ramiflorum extracts, the plant activity
against Plasmodium falciparum was evaluated in vitro for toxicity
towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human
monocytes isolated from peripheral blood. Six of the seven extracts tested were
active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the
aqueous extract was inactive. Overall, the plant extracts and the purified compounds
displayed low toxicity in vitro. A nonsoluble extract fraction and one purified
alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56
and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The
structure, activity and low toxicity of isositsirikine in vitro are described here
for the first time in A. ramiflorum, but only the neutral and
precipitate plant fractions were tested for activity, which caused up to 53%
parasitaemia inhibition of Plasmodium berghei in mice with
blood-induced malaria. This plant species is likely to be useful in the further
development of an antimalarial drug, but its pharmacological evaluation is still
required. 相似文献
8.
Uxmal and Tulum are two important Mayan sites in the Yucatan peninsula. The buildings are mainly composed of limestone and grey/black discoloration is seen on exposed walls and copious greenish biofilms on inner walls. The principal microorganisms detected on interior walls at both Uxmal and Tulum were cyanobacteria; heterotrophic bacteria and filamentous fungi were also present. A dark‐pigmented mitosporic fungus and Bacillus cereus, both isolated from Uxmal, were shown to be acidogenic in laboratory cultures. Cyanobacteria belonging to rock‐degrading genera Synechocystis and Gloeocapsa were identified at both sites. Surface analysis previously showed that calcium ions were present in the biofilms on buildings at Uxmal and Tulum, suggesting the deposition of biosolubilized stone. Apart from their potential to degrade the substrate, the coccoid cyanobacteria supply organic nutrients for bacteria and fungi, which can produce organic acids, further increasing stone degradation. 相似文献
9.
A novel neurotoxoid vaccine prevents mucosal botulism 总被引:4,自引:0,他引:4
Kobayashi R Kohda T Kataoka K Ihara H Kozaki S Pascual DW Staats HF Kiyono H McGhee JR Fujihashi K 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(4):2190-2195
The threat posed by botulism, classically a food- and waterborne disease with a high morbidity and mortality, has increased exponentially in an age of bioterrorism. Because botulinum neurotoxin (BoNT) could be easily disseminated by terrorists using an aerosol or could be used to contaminate the food or water supply, the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases has classified it as a category A agent. Although clearly the development of a safe and effective mucosal vaccine against this toxin should be a high priority, essentially no studies to date have assessed mucosal immune responses to this disease. To bridge this gap in our knowledge, we immunized mice weekly for 4 wk with nasal doses of BoNT type A toxoid and a mutant of cholera toxin termed E112K. We found elevated levels of BoNT-specific IgG Abs in plasma and of secretory IgA Abs in external secretions (nasal washes, saliva, and fecal extracts). When mice given nasal BoNT vaccine were challenged with 4 x 10(3) LD50 of BoNT type A (BoNT/A) via the i.p. route, complete protection was seen, while naive mice given the same dosage died within 2 h. To further confirm the efficacy of this nasal BoNT vaccine, an oral LD50 was determined. When mice were given an oral challenge of 5 microg (2 x oral LD50) of progenitor BoNT/A, all immunized mice survived beyond 5 days, while nonimmunized mice did not. The fecal extract samples from nasally vaccinated mice were found to contain neutralizing secretory IgA Abs. Taken together, these results show that nasal BoNT/A vaccine effectively prevents mucosal BoNT intoxication. 相似文献
10.
Further characterization of the binding of human recombinant interleukin 2 to heparin and identification of putative binding sites 总被引:1,自引:1,他引:1
We have previously provided compelling evidence that human recombinant
interleukin 2 (IL-2) binds to the sulfated polysaccharides heparin, highly
sulfated heparan sulfate and fucoidan. Here we show that IL-2 binding is
dependent on heparin chain length, but with fragments as small as 15-mers
retaining binding activity. The addition of exogenous heparin has no effect
on the in vitro biological activity of IL-2. In addition soluble IL-2
receptor alpha and beta polypeptides do not compete with heparin for the
binding of IL-2. IL-2 bound by heparin is still recognized by two IL-2
specific monoclonal antibodies, 3H9 and H2- 8, whose epitopes lie in the
amino terminal region. Murine IL-2 unlike its human counterpart fails to
bind to heparin. Human IL-2 analogs with single amino acid substitutions at
positions Lys43, Thr51, and Gln126 analogs no longer bind to heparin. By
contrast the Arg38Ala analog retains heparin full heparin binding activity.
These experimental findings together with molecular modeling studies
suggest two putative heparin binding sites on human IL-2, one involving
four basic residues, Lys48, Lys49, Lys54, and His55, and the other being a
discontinuous site comprising Lys43, Lys64, Arg81, and Arg83. Neither of
these two clusters is completely conserved in murine IL-2. Overall our data
suggest that the binding of human IL-2 to heparin and heparan sulfate does
not interfere with IL-2/IL-2 receptor interactions. Therefore, binding to
glycosaminoglycan may be a mechanism for retaining the cytokine in an
active form close to its site of secretion in the tissue, thus favoring a
paracrine role for IL-2.
相似文献