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101.
Induction of proliferation of purified human myeloid progenitor cells: a rapid assay for granulocyte colony-stimulating factors 总被引:7,自引:0,他引:7
The proliferation and differentiation of granulocyte and monocyte progenitor cells (CFU-C) in vitro is dependent on the presence of a group of closely related glycoproteins termed colony-stimulating factors (CSF). In order to investigate the interaction of these factors with CFU-C, we purified CFU-C from the peripheral blood of chronic myeloid leukemia patients with an immune rosette technique using specific monoclonal antibodies (mean 74-fold enrichment, 45% cloning efficiency). Colony formation by purified CFU-C demonstrated an absolute dependence on an exogenous source of CSF. Liquid culture of small aliquots of enriched CFU-C with CSF-containing medium resulted in a rapid, time- and concentration-dependent induction of DNA synthesis as measured by 3H-thymidine incorporation. This specific CSF induction of DNA synthesis by enriched CFU-C was used to develop a microassay system for CSF activity. CSF activity could be reproducibly quantitated in 24-48 hr. The proliferating cells in this assay system were shown to be myeloid progenitor cells by examining the morphology of their progeny and by determining the surface antigen phenotype of the responding cells (Ia+, T3-, B1-, Mo1-). This microassay provides a quantitative assessment of CSF activity that may be useful in the purification of human CSF and in the generation of monoclonal antibodies to CFU-C surface structures. 相似文献
102.
Analysis of antigenic determinants on human monocytes and macrophages 总被引:16,自引:0,他引:16
Mo1, 2, 3, and 4, and Plt-1 are a series of five distinct antigens detected on the surface of human peripheral blood monocytes by mouse monoclonal antibodies. Mo2 and 3 are restricted to the monocyte- macrophage series, while Mo1, as previously reported, is also expressed by human granulocytes and null cells. Mo3, as distinguished from Mo1 and Mo2, is weakly expressed by virgin peripheral blood monocytes but becomes well expressed if monocytes are cultured overnight at 37 degrees C. Mo4 is coexpressed by monocytes and platelets, while Plt-1 appears to be a platelet-specific antigen whose detection on monocytes reflects adherence of platelets to monocyte membranes. That Mo2-4 are true monocyte antigens is demonstrated by their resynthesis following protease treatment of monocytes (Mol expression is resistant to proteolytic digestion). During myeloid-monocyte differentiation, the Mo antigens are infrequently expressed by immature myeloid cells but are found at higher frequency on leukemic monocytic forms. Macrophages from cultured peripheral blood monocytes and HL-60 cells exposed to lymphokines or phorbol diester express Mo1-4, but noncirculating peritoneal macrophages lack Mo3. The Mo antigens are differentiation markers whose expression reflects membrane heterogeneity during myeloid- monocyte-macrophage maturation. 相似文献
103.
Isolation of myeloid progenitor cells from peripheral blood of chronic myelogenous leukemia patients 总被引:12,自引:0,他引:12
Myeloid progenitor cells (colony- and cluster-forming cells in semisolid medium, CFU-GM) were purified from the peripheral blood of chronic myelogenous leukemia (CML) patients. Lymphocytes, monocytes, and most immature myeloid cells were simultaneously depleted with specific monoclonal antibodies using an erythrocyte rosette technique for cell separation. Cells expressing Ia-like antigen were then selected from the residual cell population. Day 7 CFU-GM were enriched 44--116-fold in the IA+ cell fraction, when compared to the unseparated cells, and up to 47% of the cells could form a myeloid colony or cluster in culture. This cell fraction contained up to 92% undifferentiated blasts, with the remainder mostly promyelocytes. The enriched CFU-GM cells were dependent on an exogenous supply of colony- stimulating factor for growth, and colony formation was linear with cell concentration over a large range (10(4)-10(1) cells/ml). This technique of rosette depletion and enrichment with specific monoclonal antibodies provides a unique method for purifying a homogenous population of myeloid precursor cells with defined surface antigen characteristics. 相似文献
104.
ANNA SF LOK 《Journal of gastroenterology and hepatology》2004,19(S7):S114-S117
Abstract Occult hepatitis B virus (HBV) infection is generally defined as the detection of HBV-DNA in the serum or liver tissue of patients who test negative for hepatitis B surface antigen. In most cases, occult HBV infection is related to low level HBV infection with subdetectable levels of HBsAg and not infection with HBV variants that cannot express S proteins or produce S proteins with aberrant epitopes that are not detected by conventional serological assays. Prevalence of occult HBV infection is related to the overall prevalence of HBV infection in that country, being more common in persons with prior exposure to HBV. Occult HBV infection has been found in a substantial proportion of patients with cirrhosis and hepatocellular carcinoma but other causes of liver disease are frequently present. Future studies should focus on delineating the pathogenic role of occult HBV infection and the basis for failure to detect circulating hepatitis B surface antigen. 相似文献
105.
A carboxyl terminal truncation mutant of CD36 is secreted and binds thrombospondin: evidence for a single transmembrane domain 总被引:3,自引:0,他引:3
CD36 has been implicated in several intracellular signalling events, including platelet and monocyte activation, and receptor-mediated internalization of bound ligands such as oxidized low-density lipoprotein and apoptotic neutrophils. These processes are presumably mediated by the intracytoplasmic domain(s) of the molecule. By analysis of hydrophobicity plots and by analogy to rat LIMPII, which has a 60% homology to CD36, a two-transmembrane domain model has been proposed. To characterize the structure-function relationships of CD36 involved in transducing the signal, we have defined the number of transmembrane and intracellular domains experimentally using a mutagenesis approach. A truncated CD36 cDNA was constructed that encodes a protein that terminates just proximal to the putative C-terminal transmembrane domain. This mutant was cloned into eukaryotic expression plasmid vectors to generate short-term and stable transfected cells. Our results indicate that the truncated mutant is secreted by the transfectants into the postculture medium, indicating that there is only one transmembrane domain in CD36, which is present at the C- terminal end. The soluble secreted protein from all of these cells is functional as indicated by its binding to thrombospondin. 相似文献
106.
Quantitative parameters of myocardial perfusion with contrast echocardiography in human beings: Influence of triggering mode 总被引:1,自引:0,他引:1
Constadina J. Aggeli MD Sarah Shimoni MD Sherif F. Nagueh MD William A. Zoghbi MD 《Journal of the American Society of Echocardiography》2002,15(12):1432-1439
To facilitate quantitation of myocardial contrast echocardiography (MCE) in human beings, dual- or triple-triggered flash imaging has been advocated. However, the effect of this modality on quantitative blood-flow parameters of MCE is not known. Accordingly, MCE was quantitated in 71 myocardial regions of 22 patients (age: 57 +/- 16 years) during continuous infusion of Optison (12-18 mL/h). Two sets of images with end-systolic gating (1:1, 1:2, 1:3, 1:4, 1:6, and 1:8) from the apical 4-chamber view were acquired: single and dual triggering for the first 15 patients; and single and triple triggering for the other 7 patients. During gated imaging, MCE of the first, second, and third frame were quantitated. Curves of intensity versus pulsing intervals were fitted to an exponential function: y = A (1-e(-betat)). Where beta is myocardial blood velocity or the rate of rise of myocardial contrast intensity (MCI), and A is myocardial blood volume or the plateau of MCI reached. Continuous imaging, and the second and third frame in 1:1 gating only, provided similar intensity to precontrast imaging. Beyond 1:1 gating, MCI of the second frame in dual triggering mode gradually increased with incremental pulsing interval. This was still present but less pronounced in triple triggering. During dual and triple triggering, a lower beta was observed compared with single triggering. Application of image subtraction with the flash procedure further decreased beta, A, and the A(*)beta product, a quantitative parameter of blood flow by MCE. Thus, flash subtraction imaging alters the quantitative parameters of myocardial blood velocity and flow derived from MCE. Continuous imaging, and the second or third frame in flash imaging at 1:1 gating only, result in MCI similar to precontrast imaging and can be used for background subtraction to quantitate MCE parameters. 相似文献
107.
108.
Osio A Tan L Chen SN Lombardi R Nagueh SF Shete S Roberts R Willerson JT Marian AJ 《Circulation research》2007,100(6):766-768
Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in sarcomeric proteins (excluding phenocopy). The causal genes in approximately one-third of the cases remain unknown. We identified a family comprised of 6 clinically affected members. The phenotype was characterized by early onset of symptoms, pronounced cardiac hypertrophy, and cardiac arrhythmias. We excluded MYH7, MYBPC3, TNNT2, and ACTC1 as the causal gene either by direct sequencing or by haplotype analysis. To map the putative candidate sarcomeric gene, we perforbold locus-specific haplotyping to detect cosegregation of the locus haplotype with the phenotype, followed by mutation screening. We genotyped 5 short-tandem-repeat markers that spanned a 4.4-centimorgan region on 4q26-q27 locus and encompassed myozenin 2 (MYOZ2), a Z-disk protein. The maximum logarithm of odds score was 2.03 (P=0.005). All affected members shared a common haplotype, implicating MYOZ2 as the causal gene. To detect the causal mutation, we sequenced all exons and exon-intron boundaries of MYOZ2 in 10 family members and identified a T-->C missense mutation corresponding to S48P substitution, which cosegregated with inheritance of HCM (N=6). It was absent in 4 clinically normal family members and in 658 additional normal individuals. To determine frequency of the MYOZ2 mutations in HCM, we sequenced MYOZ2 in 516 HCM probands and detected another missense mutation (I246M). It was absent in 2 normal family members and 517 controls. Both mutations affect highly conserved amino acids. We conclude MYOZ2 is a novel causal gene for human HCM. 相似文献
109.
BACKGROUND: Tissue Doppler (TD) echocardiographic imaging of mitral and tricuspid annulus has been applied to assess right ventricular (RV) and left ventricular (LV) function in many cardiac diseases, but its clinical application, including response to long-term targeted therapy in patients with idiopathic pulmonary hypertension (PH), has not been addressed. METHODS: Seventy patients with idiopathic PH were compared with 35 age-matched control subjects to examine myocardial velocities by TD. Of these, 35 patients underwent repeat imaging after long-term targeted therapy. In addition, 50 consecutive patients with idiopathic PH with simultaneous right-heart catheterization and echocardiography were examined. RESULTS: No significant differences were noted between PH patients and the control group in lateral mitral annulus systolic velocity and early diastolic velocity (Ea) by TD, but septal velocities were significantly lower (p < 0.01). With targeted therapy, myocardial velocities at the septum and RV free wall increased significantly (p < 0.05). Likewise, E/Ea ratio increased, albeit still in the normal range. In all 50 patients with invasive measurements, lateral E/Ea ratio readily identified normal mean pulmonary capillary wedge pressure (PCWP). CONCLUSIONS: TD imaging of the lateral mitral annulus can reliably predict the presence of normal/reduced mean PCWP in patients with idiopathic PH, and track the improvement in RV function and LV filling with long-term targeted therapy. 相似文献
110.