环孢菌素A对再生障碍性贫血患者骨髓细胞Fas表达及凋亡率的影响

目的：研究环孢菌素A（CsA）联用方案对再生障碍性贫血患者骨髓细胞Fas表达及单个核细胞（MNC）凋亡率的影响。方法选择医院2010年2月至2014年2月确诊为再生障碍性贫血患者48例,分为重型再生障碍性贫血（SAA）组和慢性再生障碍性贫血（CAA）组,各24例。两组患者均予以常规十一酸睾酮、丙种球蛋白及环孢菌素A治疗,SAA组加用抗人T细胞猪免疫球蛋白（ATG）治疗。结果 SAA组总有效率为66.67%,与CAA组的87.50%相比,差异无统计学意义（ P＞0.05）;但SAA组明显缓解率显著低于CAA组( P＜0.05)。两组治疗前CD34+ Fas+细胞百分率相比,差异无统计学意义（ P＞0.05）,但治疗后SAA组明显高于CAA组（ P＜0.05）。SAA组治疗后MNC凋亡率为(2.92±1.20)%,显著低于治疗前（ P＜0.05）;CAA组治疗后MNC凋亡率为（2.27±0.74）%,显著低于治疗前的（6.46±2.17）%及SAA组治疗后的（2.92±1.20）%（ P＜0.05）。结论细胞Fas异常表达和再生障碍性贫血发病有一定联系,采用环孢菌素A联用方案治疗,可明显降低其骨髓MNC凋亡率。     

DNA damage in intact cells induced by bacterial metabolites of chloramphenicol

Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentrations of 10(-4) M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 X 10(-5) M from 2 X 10(-3) M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.     

Patchy haemopoiesis in long-term remission of idiopathic aplastic anaemia

ABSTRACT: 13 patients with idiopathic aplastic anaemia in remission for more than 2 years were examined to define the haemopoietic status by means of bone marrow scintigraphy, ferrokinetics and bone marrow culture for haemopoietic progenitor cells. Haemoglobin levels reached the normal range in all these patients although mild neutropenia and thrombocytopenia were still observed in 5 patients. Bone marrow scintigrams using indium-111 showed normal distribution in 2, diffuse low accumulation in 3, patchy distribution in 7, and expanded distribution with patchy uptake in 1 patient. The defective haemopoiesis was also confirmed by ferrokinetic and bone marrow culture studies. The patchy haemopoiesis appears to characterize the residual marrow damage in remission of idiopathic aplastic anaemia.     

Allogeneic peripheral blood stem cell transplantation in the treatment of severe aplastic anemia and severe infection

Severeaplasticanemia (SAA)ischaracterizedbyafailureofbloodcellproductionresultinginseverepancytopeniawithamarkedlyhypocellularbonemarrow Bonemarrowtransplantation (BMT)isoneofthecurativeapproachesinpatientswithSAA Peripheralbloodstemcelltransplantation(PBSCT )hasbeenmainlyusedinthetreatmentofmalignanttumors Recently ,successfulsyngeneicandallogeneicPBSCTinpatientswithSAAwasreported ,1 3 　andsomewasasasalvagetreatmentinpatientswithSAAwhofailedtoBMT 4,5Wesuccessfullycompletedanallo…     

Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin

A severe and persistent pancytopenia occurred in a 42-year-old woman with a non-Hodgkin's lymphoma following a 10-day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU-E, BFU-E, CFU-GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E-rosette+, T gamma+, OKT8+ (suppressor/cytotoxic) T-and/or Leu 7+ natural killer (NK) lymphocytes and 50% were IgM Kappa, B1+, B-lymphocytes. In vitro erythroid culture studies were consistent with T-cell-mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10-day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T- and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.     

Successful outcome of severe aplastic anemia following Epstein-Barr virus infection

Severe aplastic anemia has been reported in children following Epstein-Barr virus (EBV) infection. The pathophysiology of disease is not known, but an immunologic mechanism is suspected because of the rapid response to steroids. A patient with severe aplastic anemia following EBV infection experienced bone marrow recovery after treatment with high-dose prednisone. After reviewing the literature it is concluded that steroid therapy is indicated in this select group of patients.     

Life-threatening haematological disorders presenting with opthalmic manifestations

Three cases are reported where life-threatening haematological disorders requiring urgent medical intervention presented initially to the ophthalmologist. Case one, chronic myeloid leukaemia, presented with bilateral leukaemic retinopathy and central retinal vein obstruction due to hyperviscosity. Case two, acute myeloid leukaemia, presented with bilateral haemorrhagic retinopathy. Case three, aplastic anaemia, presented with bilateral retinopathy due to anaemia and thrombocytopaenia resembling bilateral central retinal vein occlusion. In all three cases the presence of simultaneous bilateral retinal vascular involvement and white-centred haemorrhages suggested an underlying haematological disorder and differentiated them from typical retinal venous obstruction. Prompt identification of the underlying haematological disorder allows timely referral for potentially life-saving treatment.     

Androgen therapy in aplastic anaemia: A comparative study of high and low-doses and of 4 different androgens

A prospective randomized study of androgen therapy in aplastic anaemia (AA) was performed: 2 androgens (fluoxymesterone and norethandrolone) at high (1 mg/kg/d) and low (0.2 mg/kg/d) dose were studied on 110 patients; and 4 androgens given at high doses were objectively compared in 125 other cases. When patients are matched for AA severity there is an obvious efficiency of the high-dose androgens in the survival of the less severe cases of aplastic anaemia and in their haematological improvement. The data further show that, among the 4 androgens tested, fluoxymesterone is the most efficient and stanozolol the least. We conclude that androgen therapy is truly efficient in moderately. severe aplastic anaemia and that fluoxymesterone (1 mg/kg/d) for 18 months should be chosen as reference drug to any new androgen therapy assay.     

Coexisting Suppressor Cells for Myeloid Colony Formation in the Bone Marrow of Patients with Aplastic Anaemia

Suppressor cells for colony forming cells (CFUc) were found in the bone marrow of 1 of 6 patients with aplastic anaemia. The assay applied was based on the fact that coexisting suppressor cells are more sensitive to dilution than CFU_C, as long as adequate stimulation is provided by a source of colony stimulating activity. In the patient with suppressor cells, a 4 d trial of 1000 mg methylprednisolone per d failed to improve the blood cell production and had to be discontinued due to gastric irritation.