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排序方式: 共有180条查询结果,搜索用时 15 毫秒
111.
112.
Pluripotent hematopoietic progenitor cells (CFU-GEMM), myeloid progenitor cells (CFU-GM), and erythroid progenitors (BFU-E) were studied in midtrimester human fetuses using the mixed colony assay. All three progenitor cell populations were detected at high levels in the fetal liver from 12 to 23 wk of gestation. Stem cells were first observed in the bone marrow at 15-16 wk of gestation, although bone marrow cultures from earlier fetuses showed heavy growths of stromal cells. Spleen cultures first showed growth of stem cells at 18-19 wk, but fetal thymus showed no hematopoietic activity. Peripheral blood from four fetuses aged 13, 18, 20, and 21 wk showed very high levels of all 3 progenitor cells. The results demonstrate that hematopoietic development in the human fetus parallels that of the mouse. The observation that stromal cell development in the bone marrow precedes the appearance of hematopoietic progenitor cells suggests that they may be closely involved in stem cell growth. 相似文献
113.
Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma-interferon (gamma-IFN), or tumor necrosis factor-alpha (TNF-alpha) triggered the rapid, stable phosphorylation of a 75-Kd protein (p75) when incubated with permeabilized HL60 human myeloid leukemia cells in the presence of [gamma-32P] ATP. Among several chemical inducers of HL60 cell differentiation, dimethyl sulfoxide also triggered p75 labeling, but retinoic acid or 12-O-tetradecanoylphorbol-13-acetate did not elicit this response. Pretreatment of cells with G-CSF or GM-CSF for more than 30 seconds before permeabilization rendered the p75 labeling undetectable, suggesting that ligand-stimulated labeling was rapidly completed within this time in intact cells. Phosphorylation of p75 occurred on serine and tyrosine residues. This conclusion was confirmed by direct phosphoamino acid analysis. Immunoblot analysis of lysates of intact HL60 cells that had been incubated with G-CSF, GM-CSF, IFN, or TNF confirmed that tyrosine phosphorylation of a p75 also occurred in response to these cytokines in intact cells. Pretreatment of intact HL60 cells with one biologic agent or dimethyl sulfoxide abolished p75 labeling in response to incubation of permeabilized cells with a second agent, strongly suggesting that the same protein was phosphorylated in response to these treatments. p75 labeling was strictly dependent on expression of the appropriate ligand receptor. Data suggest that activation of a tyrosine kinase system is an early response to the binding of G-CSF, GM-CSF, TNF, or IFN to their respective cell surface receptors, or to the addition of dimethyl sulfoxide, and that the resulting phosphorylation event(s) may play a role in securing common elements in the biologic responses to these agents. 相似文献
114.
Heslop HE; Gottlieb DJ; Bianchi AC; Meager A; Prentice HG; Mehta AB; Hoffbrand AV; Brenner MK 《Blood》1989,74(4):1374-1380
Interleukin-2 (IL-2) therapy may improve immune reconstitution and reduce the risk of leukemic relapse in the setting of minimal residual disease by augmenting cytotoxic effector mechanisms directed at residual malignant cells. In addition, IL-2 in vitro promotes the release of cytokines including gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF), which also possess antileukemic activity and can enhance granulocyte function. To determine if IL-2 infusion induces release of gamma-IFN and TNF in vivo in sufficient quantity to mediate these effects, we have measured serum levels of these cytokines and secretion by lymphocytes obtained from patients receiving this cytokine in a phase 1 trial. Serum gamma-IFN was undetectable pre-IL-2 and increased to 1.5 to 17 U/mL during IL-2 infusion (P less than .05). Culture of patient lymphocytes for 48 hours produced 1.2 U gamma-IFN/2 x 10(6) cells/mL pre-IL-2 rising to 50 U/2 x 10(6) cells/mL when the lymphocytes were obtained during therapy (P less than .05). Lymphocyte subset analysis showed that both CD3+ and CD16+ cells secreted gamma- IFN in response to IL-2. TNF secretion by lymphocytes also rose during IL-2 infusion from a mean of 5 U/mL to 14.4 U/mL (P less than .01) although no rise was seen in serum levels. The material secreted by IL- 2-stimulated lymphocytes is bioactive as addition of supernatants from lymphocytes obtained during IL-2 therapy to cultures of myeloid blasts significantly inhibited clonogenic growth. IL-2-induced secretion of these cytokines mediated this inhibition as it could be partially blocked by either anti-gamma-IFN or anti-TNF antibodies. Preincubation of granulocytes with the same supernatants produced enhanced oxidative metabolism, measured by chemiluminescence in response to N-formyl- methionyl-leucyl-phenylalanine (FMLP). This effect also could be partially abrogated by anti-gamma-IFN and anti-TNF antibodies. Therefore, secondary cytokine secretion may boost granulocyte function and contribute to the antileukemic effects of IL-2 infusion in patients following bone marrow transplantation or chemotherapy. 相似文献
115.
The uptake of 57Co-cyanocobalamin (CN-Cbl) and its conversion to 5- deoxyadenosylcobalamin (Ado-Cbl), methylcobalamin (Me-Cbl), and hydroxocobalamin (OH-Cbl) has been studied in phytohemagglutinin (PHA)- transformed lymphocytes from normal subjects and patients with patients with pernicious anemia. Uptake and conversion were much greater by PHA- stimulated lymphocytes than by mature non-transformed lymphocytes. In normal cells, uptake of 57Co-CN-Cbl and synthesis of the cobalamin coenzymes were approximately linear between 3 and 48 hr incubation. Ado- Cbl was the major cobalamin formed, and after 72 hr the cells contained about twice as much Ado-Cbl as Me-Cbl. Uptake by lymphocytes from patients with untreated pernicious anemia (PA) was greater than that by normal lymphocytes, but the proportions of Ado-Cbl and Me-Cbl synthesized by each were similar. Folic acid and methyltetrahydrofolate enhanced synthesis of Me-Cbl both in normal and in PA cells, while methotrexate and 5-fluorouracil depressed it. This depression was overcome by 5-formyltetrahydrofolate, suggesting that an uninterrupted folate cycle may play an important role in Me-Cbl synthesis. 相似文献
116.
Ho AD; Ganeshaguru K; Knauf WU; Dietz G; Trede I; Hunstein W; Hoffbrand AV 《Blood》1988,72(6):1884-1890
Deoxycoformycin (DCF), an adenosine deaminase (ADA) inhibitor, has been shown to be active in lymphoid neoplasms. The mechanism of cytotoxicity might involve accumulation of deoxyadenosine triphosphate (dATP), depletion of the nicotinamide adenine dinucleotide (NAD) and ATP pool, induction of double-stranded DNA strand breaks, or inhibition of S- adenosyl homocysteine hydrolase (SAH-hydrolase). We have investigated the biochemical changes in the circulating malignant cells of patients with chronic leukemia/lymphoma who were treated with DCF (4 mg/m2 weekly). Blood samples were taken from 17 patients with 60% or more circulating leukemic cells before, 4, 24, and 48 hours and five days after the first administration of DCF. Leukemic cells were separated and studied for changes in ADA, dATP, ATP, NAD, and SAH-hydrolase levels and DNA strand breaks and the data analyzed according to clinical response. Inhibition of ADA activity was found in all except one patient at 4 to 24 hours after the first administration of DCF. dATP started to accumulate at four hours, reached a maximum level between 24 and 48 hours, and returned to base values on the fifth day. Intracellular ATP and NAD levels were transiently reduced in some of the patients. However, no correlation between these changes and a clinical response could be found. DNA strand breaks could be studied in 13 patients. A significant increase in DNA breaks at 24 to 48 hours was found in six of the seven responders but only in one of the six nonresponders. At 24 hours, SAH-hydrolase levels were reduced in all seven responders studied, but only in two of the seven nonresponders. The difference in inhibition of SAH-hydrolase was statistically significant (P = .0023). These results suggest that DNA strand breaks and inhibition of SAH-hydrolase correlate with clinical response. 相似文献
117.
AV Navaratnam R Ariyaratnam NJ Smart M Parker RW Motson TH Arulampalam 《Annals of the Royal College of Surgeons of England》2015,97(1):17-21
IntroductionIncisional hernia is a common complication of laparoscopic colorectal surgery. Extraction site may influence the rate of incisional hernias. Major risk factors for the development of incisional hernias include age, diabetes, obesity and smoking status. In this study, we investigated the effect of specimen extraction site on incisional hernia rate.MethodsTwo cohorts of patients who underwent laparoscopic colorectal resections in a single centre in 2005 (n=85) and 2009 (n=139) were studied retrospectively. In 2005 all specimens were extracted through transverse muscle cutting incisions. In 2009 all specimens were extracted through midline incisions. Demographic variables, rate of incisional hernias and risk factors for hernia development were compared between the year groups. All patients had been followed up clinically for two years.ResultsA total of 224 patients (mean age: 67.5 years, standard deviation: 16.35 years) were included in this study. Of these, 85 patients were in the 2005 transverse group and 139 were in the 2009 midline group. The total incisional hernia rate for the series was 8.0% at the two-year follow-up visit. For the 2005 group, the incisional hernia rate was 15.3% (n=13) and for the 2009 group, it was 3.6% (n=5) (p<0.01). The body mass index was higher in patients who developed incisional hernias than in those who did not (p=0.02).ConclusionsThe 2005 group had a significantly higher incisional hernia rate than the 2009 group. This is due to the differences in the incision technique and extraction site between the two groups. 相似文献
118.
Moses AV; Williams S; Heneveld ML; Strussenberg J; Rarick M; Loveless M; Bagby G; Nelson JA 《Blood》1996,87(3):919-925
The majority of human immunodeficiency virus (HIV)-seropositive patients develop bone marrow abnormalities associated with hematopoietic malfunction during the progression of disease. One important manifestation of HIV-associated hematopoietic dysfunction is that after myelosuppression, bone marrow recovery, a process known to be mediated in part by the production of stromal cell-derived hematopoietic growth factors, is impaired. We sought to test the hypothesis that bone marrow stromal cells are infected by HIV-1 in vivo and that production of certain stromal cell-derived hematopoietic growth factors is deficient as a consequence. In this report, we demonstrate that bone marrow microvascular endothelial cells (MVEC), a key element of the stroma, are the predominant cells infected by HIV (5% to 20%) in bone marrow stromal cultures obtained from 11 consecutive HIV-seropositive patients. Although HIV-infected stromal cultures enriched for MVEC constitutively express normal levels of interleukin (IL)-4, IL-6, granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, tumor necrosis factor (TNF)- alpha, transforming growth factor (TGF)-beta, and Steel factor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly reduced in these cultures. These observations suggest that HIV infection of bone marrow MVEC reduces the capacity of hematopoietic stroma to respond to regulatory signals that normally augment blood cell production during periods of increased demand. 相似文献
119.
We report here experiments on the analysis of cellular signal transduction in a series of patients with chronic B cell disorders (B cell chronic lymphocytic leukemia [B-CLL] and prolymphocytic leukemia). We compared the response of the leukemic cells with primary external signals (interleukin 2 [IL-2] or B cell differentiation factors [BCDF or IL-6]) with their response to secondary inducers (the phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA] or the calcium ionophore A23187) that circumvent the first part of the signal transduction pathway by directly activating the key enzyme protein kinase C. One BCDF was synthesized by mitogen-activated peripheral blood B lymphocytes; a second BCDF was constitutively produced by the human bladder carcinoma cell line T24. Changes in morphology, Tac (IL-2 receptor) expression, RNA synthesis measured by 3H-uridine uptake, and immunoglobulin production tested by enzyme-linked immunosorbent assay were used as parameters of successful signal transduction. TPA alone and TPA plus A23187 (synergistically) effectively initiated differentiation in all the leukemia cases. Neither IL-2 nor BCDF (singly or in combinations) caused equivalent responses. On the other hand, IL-2 and BCDF produced a substantial differentiation effect on normal B lymphocytes. Our data suggest that (a) B-CLL cells are able to respond to direct stimulation of the second messenger pathway (through protein kinase C) but not to the physiological stimuli IL-2 or BCDF; (b) the defect in signal transduction appears to be located upstream of protein kinase C (a possible candidate is a G protein); (c) malignant B cells may spontaneously or after treatment with inducers express the IL- 2 receptor (Tac antigen) in the absence of a functional differentiating response to IL-2; and (d) signs of proliferation/differentiation in B- CLL samples after incubation with IL-2 or BCDF might be due to contamination of the cell populations with residual normal B cells. 相似文献
120.
Mannose binding protein deficiency is not associated with malaria, hepatitis B carriage nor tuberculosis in Africans 总被引:10,自引:0,他引:10
Bellamy R; Ruwende C; McAdam KP; Thursz M; Sumiya M; Summerfield J; Gilbert SC; Corrah T; Kwiatkowski D; Whittle HC; Hill AV 《QJM : monthly journal of the Association of Physicians》1998,91(1):13-18
We retrospectively studied MBP genotypes in patients with malaria,
tuberculosis (TB), and persistent hepatitis B virus (HBV) carriage, in
clinics and hospitals in The Gambia. Children under 10 years with cerebral
malaria and/or severe malarial anaemia, were compared with children with
symptomatic, mild malaria, and controls of the same age and ethnicity.
Adult TB cases with smear-positive pulmonary TB were compared with healthy
blood donors from the same ethnic groups. Malaria cases and controls were
tested for hepatitis B core antibody (anti-HBc) and surface antigen
(HBsAg). TB patients were tested for HIV antibodies. Genotyping used
sequence-specific oligonucleotide analysis to identify MBP variant alleles.
Overall, 46% (944/2041) of patients and controls were homozygous for the
wild-type MBP allele, 45% (922/2041) were carriers of a single variant
allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor
heterozygotes for MBP variants were at increased risk of clinical malaria,
persistent HBV carriage or TB. The most common mutation in Africans, the
codon 57 variant allele, was weakly associated with resistance to TB
(221/794 in TB cases and 276/844 in controls, p = 0.037). MBP deficiency is
not a significant risk factor for persistent HBV, severe malaria nor
pulmonary TB in West Africa.
相似文献