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31.
Gonzales AJ; Christensen JG; Preston RJ; Goldsworthy TL; Tlsty TD; Fox TR 《Carcinogenesis》1998,19(7):1173-1183
32.
Guo RJ; Wang Y; Kaneko E; Wang DY; Arai H; Hanai H; Takenoshita S; Hagiwara K; Harris CC; Sugimura H 《Carcinogenesis》1998,19(9):1539-1544
Mutations in the transforming growth factor beta type II receptor
(TGFbetaRII) gene have been detected in several human cancer types
exhibiting microsatellite instability. Using intron primers previously
reported for examination of the entire coding region of the TGFbetaRII
gene, 29 sporadic gastric cancers were screened with non-radioactive single
strand conformation polymorphism and subsequent DNA sequencing analysis.
Mutations of the TGFbetaRII gene were detected in three out of 29 tumors
(10%). Two cases showed deletions in a polyadenine tract in both alleles
and was positively associated with replication error. One case had an
insertion of GA dinucleotide sequence in one allele. Mutations of the
TGFbetaRII gene were restricted to exon 3 and other coding regions were not
affected. Loss of heterozygosity was detected by analyzing a polymorphic
site in intron 2. Three out of nine (33%) informative cases, which were all
of intestinal type and advanced cases, showed loss of heterozygosity but
neither TGFbetaRII mutation nor replication error was found in these cases.
Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different
extent in the gastric cancer with genetically abnormal transforming growth
factor. Although the numbers studied are small, homozygous (A)10 deletion
or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and
progression of at least some part of sporadic gastric cancer.
相似文献
33.
34.
Tumour cell growth may be accelerated by protein kinase C (PKC) agonists
such as phorbol esters and receptor tyrosine kinases, but receptor tyrosine
kinases are in turn desensitized to growth factors by PKC agonists. To
clarify this apparent PKC bifunctionality, we have used phosphoantibodies
to determine the relationship between PKC- dependent phosphorylation events
affecting the ErbB2 oncoprotein in G8/DHFR 3T3 cells. Neither the kinetics
nor the extent of phorbol- induced juxtamembrane domain (Thr686)
phosphorylation vary directly with C-terminal (Tyr1222) dephosphorylation,
with Tyr1222 continuing to be dephosphorylated long after Thr686
phosphorylation has also declined. Platelet-derived growth factor (PDGF)
mimics the short-term effects of phorbol on Thr686 and Tyr1222
phosphorylation, and confocal microscopy reveals that both of these PKC
agonists induce rapid internalization of PKC-modified ErbB2. Phorbol causes
sustained cytoplasmic accumulation of PKC-phosphorylated receptors,
however, whereas PDGF triggers the appearance of this ErbB2 subset only
briefly. Metabolic labelling and co-precipitation studies fail to implicate
heterologous molecules in either the tyrosine dephosphorylation or
internalization of PKC-modified ErbB2. Taken in the context of earlier
juxtamembrane domain mutagenesis studies, these findings indicate that
phorbol-activated PKC may desensitize growth factor receptors to
extracellular ligands solely by triggering sustained receptor
internalization. We submit that PKC-dependent juxtamembrane domain
phosphorylation represents a physiological mechanism for shortening the
duration and enhancing the specificity of growth factor signalling by
promoting internalization of liganded and unliganded receptors,
respectively.
相似文献
35.
36.
F.E. Fernández Suárez R. del Valle Fernández A. González Alvarez J. Sánchez Lasheras L. Fernández Sánchez L. Argüelles Tamargo 《Revista espa?ola de anestesiología y reanimación》2013,60(8):440-447
ObjectiveTo analyze the experience and anesthetic management in the transcatheter implantation of the CoreValve® self-expanding aortic valve, in a university tertiary hospital.Material and methodsObservational analytical review of data incorporated into a prospectively maintained database of 142 patients diagnosed with severe aortic stenosis who underwent implantation of a CoreValve® aortic self-expanding aortic valve between December 2007 and December 2012.ResultsThe mean age of patients was 82.5 ± 6.1 years and the logistic EuroSCORE was 14.9 ± 11.2. General anesthesia was used in 107 patients (75.3%), with local anesthesia with sedation in 35 (24.6%). Local anesthesia and sedation was associated with a lower requirement of vasoactive drugs (P = .003) during implantation. No statistically significant differences were found between the 2 anesthetic techniques in the duration of the procedure, hospital stay, or morbimortality. The success rate was 97.1%. The most common complication was conduction disorders that required implantation of a permanent pacemaker in 46 patients (32.3%). There was no intraoperative mortality, and all-cause mortality at 30 days was 6.3%, with a one-year survival estimated by the Kaplan-Meier of 83.1%.ConclusionsThis study confirms that in patients with severe aortic stenosis and high surgical risk, transcatheter implantation of aortic valve is a safe and effective alternative. Both, general anesthesia and local anesthesia with sedation are valid options, depending on the experience of the team. 相似文献
37.
38.
39.
Platelet activation leads to the incorporation of 32[PO4(2-)] into bovine coagulation factor Va and recombinant human factor VIII. In the presence of the soluble fraction from thrombin-activated platelets and (gamma-32P) adenosine triphosphate, radioactivity is incorporated exclusively into the M(r) = 94,000 heavy chain (H94) of factor Va and into the M(r) = 210,000 to 90,000 heavy chains as well into the M(r) = 80,000 light chain of factor VIII. Proteolysis of the purified phosphorylated M(r) = 94,000 factor Va heavy chain by activated protein C (APC) gave products of M(r) = 70,000, 24,000, and 20,000. Only the intermediate M(r) = 24,000 fragment contained radioactivity. Because the difference between the M(r) = 24,000 and M(r) = 20,000 fragments is located on the COOH-terminal end of the bovine heavy chain, phosphorylation of H94 must occur within the M(r) = 4,000 peptide derived from the carboxyl-terminal end of H94 (residues 663 through 713). Exposure of the radioactive factor VIII molecule to thrombin ultimately resulted in a nonradioactive light chain and an M(r) = 24,000 radioactive fragment that corresponds to the carboxyl-terminal segment of the A1 domain of factor VIII. Based on the known sequence of human factor VIII, phosphorylation of factor VIII by the platelet kinase probably occurs within the acidic regions 337 through 372 and 1649 through 1689 of the procofactor. These acidic regions are highly homologous to sequences known to be phosphorylated by casein kinase II. Results obtained using purified casein kinase II gave a maximum observed stoichiometry of 0.6 mol of 32[PO4(2-)]/mol of factor Va heavy chain and 0.35 mol of 32[PO4(2-)]/mol of factor VIII. Phosphoamino acid analysis of phosphorylated factor Va by casein kinase II or by the platelet kinase showed only the presence of phosphoserine while phosphoamino acid analysis of phosphorylated factor VIII by casein kinase II showed the presence of phosphothreonine as well as small amounts of phosphoserine. The platelet kinase responsible for the phosphorylation of the two cofactors was found to be inhibited by several synthetic protein kinase inhibitors. Finally, partially phosphorylated factor Va was found to be more sensitive to APC inactivation than its native counterpart. Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II- like kinase may downregulate the activity of the two cofactors. 相似文献
40.
Engraftment of dogs with Ia-positive marrow cells isolated by avidin- biotin immunoadsorption 总被引:3,自引:0,他引:3
Berenson RJ; Bensinger WI; Kalamasz D; Schuening F; Deeg HJ; Graham T; Storb R 《Blood》1987,69(5):1363-1367
Previous work has shown failure of engraftment in lethally irradiated dogs when autologous marrow was depleted of Ia-positive cells with an anti-Ia antibody and complement before infusion. In the current study, we have utilized an avidin-biotin immunoadsorption procedure to obtain a population of highly enriched Ia-positive cells for autologous bone marrow transplantation in dogs given lethal irradiation. Dog marrow cells (2.4 to 7.0 X 10(9) cells) that contained 8.6% to 19.9% Ia- positive cells were treated successively with monoclonal antibody 7.2, which reacts with a framework determinant of Ia-antigen, and biotin- conjugated goat antimouse immunoglobulin. These treated cells were passed over a column of avidin-Biogel (polyacrylamide) and the adherent cells removed by mechanical agitation. Seven lethally irradiated dogs were transplanted with 5.9 to 33.4 X 10(6) recovered adherent cells per kilogram of which 69.0% to 88.0% were Ia-positive. All dogs had hematologic recovery; six are alive and well with durable engraftment and one died on day 15 posttransplant. They are immunologically normal as determined by lymph node and bone marrow biopsies, lymphocyte function, and immunophenotyping of peripheral blood and bone marrow cells. These data provide further evidence that canine hematopoietic stem cells express Ia-like antigens and that these cells are capable of complete hematopoietic and immunologic reconstitution in an autologous model. 相似文献