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101.
卡世全 《中国肝脏病杂志(电子版)》2012,4(1):20-22
目的观察六味五灵片联合替比夫定治疗活动性慢性乙型肝炎(CHB)肝硬化的临床疗效。方法将72例HBV DNA、HBeAg阳性的CHB肝硬化患者随机分为治疗组和对照组,两组均为36例。治疗组给予六味五灵片联合替比夫定治疗,对照组单用替比夫定治疗,疗程均为24周。治疗前后分别检测患者肝功能、慢性HBV标志物、HBV DNA低于检测下限的比率。结果治疗组血清ALT、AST下降明显,与对照组比较,差异有统计学意义(P〈0.05),治疗组HBeAg低于检测下限的比率及HBeAg/抗-HBe血清转换率均高于对照组,治疗组总有效率高于对照组,差异有统计学意义(P〈0.05)。结论六味五灵片联合替比夫定治疗活动性CHB肝硬化疗效显著,不良反应发生率小,疗效优于单一用药组,是治疗活动性CHB肝硬化的有效方法。 相似文献
102.
Chromosome 7 long arm deletion in myeloid disorders: a narrow breakpoint region in 7q22 defined by molecular mapping 总被引:5,自引:0,他引:5
Kere J; Ruutu T; Davies KA; Roninson IB; Watkins PC; Winqvist R; de la Chapelle A 《Blood》1989,73(1):230-234
The involvement of the erythropoietin (EPO), plasminogen activator inhibitor type I (PAI1), and multi-drug resistance (MDR2) genes located in chromosomal region 7q21-22 was studied in patients with myeloid disorders and with or without a chromosome 7 abnormality. Separated blood mononuclear cells and granulocytes from 21 patients were used in restriction fragment length polymorphism (RFLP) studies with gene- specific DNA probes. A marked weakness of one of the allelic bands was observed in granulocyte-derived DNA from heterozygous patients with monosomy 7. In four patients with a partial deletion of chromosome 7 long arm (7q-), marked weakness of an allelic band was observed in granulocyte-derived DNA with PAI1 probe (four heterozygous patients) and MDR2 probe (one heterozygous patient), implying deletion of these genes. In contrast, the EPO gene was not deleted in these patients, as demonstrated by the presence of two allelic bands of equal strength in granulocyte-derived DNA (two patients) or by gene dosage estimation (two patients). Two allelic bands of equal strength were also observed in three heterozygous patients with an arbitrary probe (pKV13) located in 7cen-q21.3. Unexpected hemizygosity or hybridization bands were not observed in any patient. We conclude that PAI1 and MDR2 are located distally of EPO in 7q22, and that none of these genes is commonly rearranged in myeloid disorders. The chromosome 7 long arm deletion breakpoint is located in a relatively narrow segment between the PAI1 and EPO genes in different patients. The deletion may involve a specific site in DNA, since the genetic distance between the PAI1 and EPO genes is only 3 cM. 相似文献
103.
al-Shahi R; Mason JC; Rao R; Hurd C; Thompson EM; Haskard DO; Davies KA 《Rheumatology (Oxford, England)》1997,36(7):794-798
Thrombocytopenia in patients with acute systemic lupus erythematosus (SLE)
frequently presents the clinician with considerable diagnostic and
therapeutic difficulties. In this Grand Round, we present a 48-yr- old
woman with a 7 yr history of lupus, who presented with acute proliferative
glomerulonephritis and nephrotic syndrome, pneumonia, profound
hypocomplementaemia and a severe microangiopathic haemolytic anaemia with
associated thrombocytopenia. Her thrombocytopenia proved initially
refractory to conventional immunosuppressive therapy, and corticosteroids,
and resolved only with plasma exchange and repeated fresh frozen plasma
infusions. Serological testing revealed high-titre antinuclear antibodies
(ANA) and markedly raised antibodies to double- stranded (ds) DNA, but no
significant elevation in anticardiolipin antibodies. Platelet-associated
IgG and IgM and antibodies to the CD36 glycoprotein antigen, expressed on
platelets and endothelium, were detected in the serum. We address some of
the difficult diagnostic and management issues raised by this complex
patient and the possible immunopathological links between antibodies to
CD36, immune-mediated red cell destruction, thrombocytopenia and thrombotic
microangiopathic haemolytic anaemia.
相似文献
104.
Faltynek CR; Princler GL; Rossio JL; Ruscetti FW; Maluish AE; Abrams PG; Foon KA 《Blood》1986,67(4):1077-1082
Patients with hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) were treated with recombinant interferon alpha A (rIFN- alpha A). The binding of iodinated recombinant interferon-alpha to baseline samples of peripheral blood mononuclear cells (PBMCs) from the leukemia patients was compared with clinical responsiveness to rIFN- alpha A. HCL patients (8/10) responded to rIFN-alpha A therapy, whereas none (0/10) of the CLL patients studied responded. The PBMCs from the eight responsive HCL patients bound approximately twice as much iodinated interferon as the PBMCs from nonresponsive CLL patients. This difference was due to more high-affinity receptors per cell with no difference in the affinity of the interferon-receptor interaction. However, because PBMCs from HCL patients were larger than PBMCs from CLL patients, the cell surface receptor density was similar. The leukemic cells from one of the two nonresponsive HCL patients bound iodinated interferon similarly to the cells from the responsive HCL patients, whereas the leukemic cells from the other nonresponsive HCL patient bound considerably less. The rapidity of response of the HCL patients did not correlate with the level of binding of iodinated interferon. Our results suggest that the absolute number of interferon receptors per cell may be only one of several important parameters in the response to rIFN-alpha A therapy, and that the responsiveness of a particular lymphoproliferative disease or a particular patient to rIFN- alpha A therapy cannot be predicted or explained solely by the degree of interaction between IFN and its cell surface receptor. 相似文献
105.
The activation of the contact phase of coagulation by physiologic surfaces in plasma: the effect of large negatively charged liposomal vesicles 总被引:1,自引:0,他引:1
The endogenous, negatively charged surface that induces activation of the contact coagulation factors was investigated in plasmas taken from women in late pregnancy and control subjects of child-bearing age. The plasmas from the two groups of subjects were incubated at 4 degrees C for 24 hours either in plastic or in glass tubes and the factor VII coagulant activity (VIIc) was assayed in the treated plasmas. The activation of factor VII under these conditions involves the generation of enzymes derived from factor XII (XIIa). The contact surface is rate- limiting for the activation of factor VII in the plasmas in both groups of subjects and can be supplemented by large multilamellar liposomal vesicles carrying the appropriate density of negative charge. The size of these vesicles is within the range of sizes of the large lipoprotein particles (chylomicrons, very low and intermediate-density lipoproteins). The relationship between the density of negative charge on the liposomal vesicles and VIIc was similar in the late pregnancy and the control plasmas incubated in plastic tubes. At a saturating density of negative charge the observed relative VIIc was similar in both sets of plasmas. The incubation of late pregnancy or control plasma in plastic tubes in the presence of sodium stearate caused VIIc to increase with increasing concentration of the added fatty acid. These results suggest that large lipoprotein particles carrying the appropriate free fatty acid at a sufficient density of negative charge could provide the contact surface that induces the generation of factor XIIa and the subsequent activation of factor VII. Moreover, plasmas from women in late pregnancy have a higher concentration of potential surface and a higher density of negative charge than the plasmas from nonpregnant women. 相似文献
106.
Factor V and factor VIII are homologous cofactors in the blood coagulation cascade that have the domain structure A1-A2-B-A3-C1-C2, of which the B domain has extensively diverged. In transfected COS-1 monkey cells, expression of factor VIII is approximately 10-fold less efficient than that of factor V, primarily because of inefficient protein secretion and, to a lesser extent, reduced mRNA expression. To study the functional significance and effect of the B domain on expression and activity, chimeric cDNAs were constructed in which the B domains of factor V and factor VIII were exchanged. Expression of a factor VIII chimera harboring the B-domain of factor V yielded a fully functional factor VIII molecule that was expressed twofold more efficiently than wild-type factor VIII because of increased mRNA expression. Thus, sequences within the factor VIII B domain were not responsible for the inefficient secretion of factor VIII compared with factor V. Expression of a factor V chimera harboring the B domain of factor VIII was slightly reduced compared with wild-type factor V, although the secreted molecule had significantly reduced procoagulant activity correlating with dissociated heavy and light chains and resistance to thrombin activation. Interestingly, the factor V chimera containing the factor VIII B domain was efficiently activated by Russell's viper venum (RVV). A factor V B domain deletion (residues 710- 1545) molecule also exhibited significantly reduced procoagulant activity caused by resistance to thrombin cleavage and activation, although this molecule was activatable by RVV. These results show that, in contrast to factor VIII, thrombin activation of factor V requires sequences within the B domain. In addition, thrombin activation of factor V occurs through a different mechanism than activation by RVV. 相似文献
107.
Brennan FM; Browne KA; Green PA; Jaspar JM; Maini RN; Feldmann M 《Rheumatology (Oxford, England)》1997,36(6):643-650
Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum
samples from rheumatoid arthritis (RA) patients undergoing a double-blinded
placebo-controlled trial with the chimaeric anti-tumour necrosis factor
(TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent
MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the
commencement of the trial compared with normal control sera. Following cA2
therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10
mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10
mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at
all time points was observed, reducing maximally to 41% of pre-infusion
values at day 7. MMP-1 levels were also reduced, but less dramatically than
MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2
treated group. In a separate non-placebo-controlled study, we also
evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in
plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the
normal control range, but were significantly reduced (P < 0.035) 14 days
after infusion to 72% of pre-infusion values. This study confirms previous
reports that MMP-3 levels are elevated and correlate with measures of
inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1
levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst
serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to
and following anti-TNF-alpha antibody therapy, it remains to be
demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and
bone resorptive processes which are evident in this disease.
相似文献
108.
We have recently described a marrow stroma-dependent long-term culture system that supports differentiation of CD34+ human marrow primitive progenitors into natural killer (NK) cells. We postulate that CD7 expression may be an early event in commitment of hematopoietic progenitors to the NK lineage. Here we compare the characteristics of CD34+7- and CD34+7+ marrow cells cultivated in the stroma-based NK culture system. These CD34+ populations were further compared with a marrow derived, more committed, CD34-7+ progenitor to emphasize the continuum of NK development and to highlight differences between progenitors in our assays. No progenitor proliferated when plated in media without stroma, underscoring the importance of stroma in NK differentiation. Plating progenitor populations in interleukin-2 containing media directly on preestablished, allogeneic, irradiated marrow stroma for 5 weeks resulted in CD56+CD3- NK cells; however, characteristics of the cultured populations differed. Fold expansion and cloning efficiency of the CD34+7+ population, determined by a functional limiting dilution assay was significantly higher than of the CD34+7- or CD34+7+ populations. This suggests that the CD34+7+ population is highly enriched for an NK progenitor and a possible intermediate in NK lineage differentiation. Further dividing the CD34+7+ population by the relative fluorescence of CD7 into CD34+7+dim and CD34+7+bright populations showed that the CD34+7+bright population exhibited a significantly higher cloning frequency than parallel experiments with CD34+7+dim cells (11.8% +/- 2.4% v 2.4% +/- 0.7%, n = 6; P = .005). Plating of the more primitive CD34+7- population in a transwell system (which separates progenitors from stroma by a microporous membrane) prevents differentiation into NK cells. In contrast, plating of CD34+7+ progenitors in transwells resulted in generation of NK cells. These data suggest that primitive, but not more mature NK progenitors may require direct contact with stroma for the initial differentiation steps. Finally, differentiation of the NK progenitors in this stroma-dependent model results in expression of CD2 not present on any of the starting populations. This observation suggests that marrow stroma can stimulate CD2 expression on NK progenitors in a previously undescribed fashion that may be analogous to the thymic effect on CD2 expression in immature T lymphocytes. These observations identify early steps in the commitment of primitive marrow CD34+ hematopoietic progenitors to a lymphoid lineage and underscore the importance of coexpression of CD7 with CD34 as an early lymphoid commitment characteristic and direct progenitor-stroma interactions in this process. 相似文献
109.
Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis 总被引:12,自引:0,他引:12
We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena. 相似文献
110.
Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone. 相似文献