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21.
Dziennis S; Van Etten RA; Pahl HL; Morris DL; Rothstein TL; Blosch CM; Perlmutter RM; Tenen DG 《Blood》1995,85(2):319-329
CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells. 相似文献
22.
23.
Georgina L Ryland Sally M Hunter Maria A Doyle Simone M Rowley Michael Christie Prue E Allan David DL Bowtell Australian Ovarian Cancer Study Group Ian G Campbell 《The Journal of pathology》2013,229(3):469-476
Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under‐described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild‐type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
24.
VY Kong B Sartorius DL Clarke 《Annals of the Royal College of Surgeons of England》2015,97(5):390-395
IntroductionAcute appendicitis in the developing world has a markedly different disease profile to that in the developed world.MethodsA retrospective study was undertaken over a four-year period at a university hospital in South Africa to review the disease spectrum and the clinical outcome of acute appendicitis.ResultsA total of 1,004 patients (54% male, median age: 18 years) with intraoperatively confirmed appendicitis were reviewed. Over half (56%) were from the urban district within the city of Pietermaritzburg and the remaining 44% were from the rural health district. The median duration of illness from onset to definitive care was 4 days. Sixty per cent of appendices were perforated and associated with intra-abdominal contamination. Forty per cent of patients required reoperation to control intra-abdominal sepsis. Ten per cent required admission to the intensive care unit. The median overall length of hospital stay was 5 days. The mortality rate was 1%.Rural patients had a longer median duration of illness (3 vs 5 days, p<0.001) as well as a more advanced disease profile associated with perforation and severe intra-abdominal sepsis (19% vs 71%, p<0.001). Female patients had a longer median duration of illness (3 vs 4 days, p<0.001), were more likely to present with severe intra-abdominal sepsis (31% vs 54%, p<0.001) and were more likely to require a laparotomy (50% vs 73%, p<0.001). The total cost of managing the entire cohort of 1,004 patients over the 4-year period was £2,060,972.ConclusionsAcute appendicitis in South Africa is a serious disease associated with significant morbidity. Late presentation is common. Female and rural patients have the worst clinical outcomes, with significant cost to the health system. 相似文献
25.
Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT. 相似文献
26.
Multiple signal transduction cascades, consisting of multiple interacting proteins, are activated following stimulation through most cell surface receptors, including the immunoglobulin receptor of B lymphocytes. In this report, we investigated the multimolecular complexes formed following anti-Ig stimulation of a human B-lymphoma cell line, resulting in activation of phosphatidylinositol 3-kinase (PI3K). PI3K is a lipid kinase that consists of an 85-kD regulatory subunit, bound to a 110-kD catalytic subunit. CD19 is a 95-kD B-cell surface marker that contains a consensus binding motif for PI3Kp85 in the cytoplasmic domain and recruits PI3K activity in activated B cells. The protein product of the c-cbl protooncogene is a 120-kD protein that is expressed in early B-lineage cells and in myeloid cells and is phosphorylated on tyrosine following receptor-mediated signaling in T and B lymphocytes. We demonstrate here that phosphorylated c-cbl complexes with CD19 and with PI3Kp85 via its C-terminal SH2 domain, and that both c-cbl and CD19 are associated with active PI3K in anti-Ig- stimulated cells. Although we cannot differentiate between a three- component, c-cbl/CD19/p85 complex and individual two-component complexes, these studies suggest that c-cbl may function as a docking protein, possibly linking distinct signal transduction pathways. 相似文献
27.
Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling 总被引:2,自引:1,他引:2
In this report we show that gamma-interferon (IFN) induces the expression of the nonreceptor protein tyrosine kinase, p72syk, and that cross-linking the Fc gamma RI receptor in IFN-differentiated U937 cells (U937IF cells) results in the activation of syk kinase. We show that syk is tyrosine phosphorylated (12-fold increase) after Fc gamma RI cross-linking. In vitro kinase assays demonstrate that the specific kinase activity of syk increased eightfold after Fc gamma RI cross- linking. The activation of signal transduction through the Fc gamma RI receptor, as measured by the respiratory burst, is associated with the tyrosine phosphorylation and catalytic activation of the syk kinase. We show that syk coprecipitates with the gamma subunit of the Fc gamma RI, Fc gamma RI gamma. The data suggest that p72syk is involved in signal transduction through the Fc gamma RI receptor, involving the Fc gamma RI gamma subunit. 相似文献
28.
Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection 总被引:2,自引:0,他引:2
Novales JS; Salva AM; Modanlou HD; Kaplan DL; del Castillo J; Andersen J; Medlock ES 《Blood》1993,81(4):923-927
Maternally administered recombinant human granulocyte colony- stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG- CSF augments neonatal defenses against a lethal bacterial challenge. 相似文献
29.
Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with allogeneic bone marrow transplantation (BMT) for lymphomas and multiple myeloma. We used the C3H 38C13 murine B-cell lymphoma, which expresses and secretes clonally derived Ig, the idiotype of which can serve as a tumor-specific antigen, to test the principle of transfer of tumor idiotype-specific immunity with BM. BALB/c marrow donors were twice immunized with 38C13-derived Ig, or with an isotype-matched control Ig, conjugated to keyhole limpet hemocyanin. Lethally irradiated C3H recipients reconstituted with marrow from idiotype immune, but not nonspecifically immune, donors demonstrated protection against subsequent lethal tumor challenge. The immunoprotective effect of immune allogeneic marrow was abrogated by T-cell depletion of the marrow graft before infusion. Low levels of serum anti-idiotypic antibody remained unaltered in recipients of T-cell-depleted immune marrow, consistent with a primary role for T-cell immunity in the cellular mechanism of this phenomenon. A modest therapeutic effect of immune allogeneic marrow was observed against 10 day, 1 cm established subcutaneous tumors, but only in combination with a booster immunization of the recipient post-BMT. These results provide the rationale for a novel strategy for enhancing the specific antitumor effect of allogeneic marrow grafts. 相似文献
30.
Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients. 相似文献