The Genetic Basis of the Interaction Between Pyrimidine 5′ Nucleotidase I Deficiency and Hemoglobin E

We have previously described a family in which the interaction between pyrimidine 5′ nucleotidase I (P5N‐I) deficiency and hemoglobin E resulted in severe haemolytic anaemia. In this study we explored the genetic basis of the severe clinical phenotype and look for evidence of the interaction between these conditions. A P5N‐I gene mutation (IVS8 + 1–2delGT) was found in the family, confirming that the severe phenotype results from the interaction between two genetic diseases.     

Balance control is impaired in adults with sickle cell anaemia

Abstract

Background: Musculoskeletal involvement and cerebrovascular disease are common in sickle cell anaemia (SCA). These changes are potentially important factors that modify the control of balance in this population.

Objective: To assess balance control in adults with SCA and investigate the associations among balance, posture and muscle function.

Methods: Twenty neurologically intact (i.e. without previous episodes of overt stroke or transient ischaemic attack) adults with SCA and 18 controls were evaluated. All participants underwent static balance measurement through stabilometry, postural evaluation through photogrammetry and assessment of muscle function through handgrip and respiratory muscle strength.

Results: Compared to the controls, the adults with SCA exhibited greater displacement of the centre of mass, particularly in the mediolateral direction. Moreover, the adults with SCA exhibited greater postural deviations for the following variables: angles of the right and left hip, horizontal asymmetry of the scapula in relation to T3, angles of the right and left leg-heel and horizontal alignment of the pelvis. Handgrip strength, respiratory muscle strength and haemoglobin (Hb) levels were significantly correlated with postural balance measurements. Significant correlations between balance and posture were only observed between the variables of balance and the postural parameters that involved the angulations calculated from the vertical alignment of the pelvis, hip and ankle.

Conclusions: Neurologically intact adults with SCA exhibit damage in static balance, particularly in the mediolateral direction. These patients present postural deviations due to changes in the hip and ankle joints. In addition, balance control is related to posture, Hb level and muscle function.     

Evaluation of concentration and storage effects of mitomycin C in the diagnosis of Fanconi anemia among idiopatic aplastic anemia patients

BACKGROUND:

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder that shows an increased sensitivity to the intercalating agents such as mytomycin C (MMC), measured as chromosomal aberrations. This study was conducted to differentiate between FA and “idiopathic” aplastic anemia on the basis of induced chromosomal breakage study with MMC.

MATERIALS AND METHODS:

MMC stress tests in different final concentrations of 20 and 50 ng/ml of MMC were conducted on peripheral blood lymphocytes from 32 patients with aplastic anemia and 13 healthy controls. Fifty nanograms per milliliter of MMC from old, fresh and frozen stocks was used to check the sensitivity of diagnosis on FA-diagnosed patients. Statistical analysis was used for the assessment of aberrations, including chromatid and chromosome breaks and exchanges.

RESULTS:

Eight patients (25%) with a very high percentage of chromosomal breakage were diagnosed as FA on the basis of the chromosomal breakage study. Six of these patients exhibited congenital anomalies at presentation, while another two lacked such anomalies or had minor physical problems. Freshly made MMC has shown more sensitivity to detect FA patients compared with frozen or 1-week-old MMC stock.

CONCLUSIONS:

The study indicates that freshly made MMC stress test provides an unequivocal means of differentiation between FA and “idiopathic” aplastic anemia. Further, the study, the first of its kind from Iran, stresses on the need for conducting this test in all aplastic anemia cases, even those without congenital anomalies, for accurate and timely diagnosis of FA to implement appropriate therapy.     

集落刺激因子治疗重型再生障碍性贫血疗效和安全性的Meta 分析

目的:通过Meta分析评价粒系或粒单系集落刺激因子(G-CSF或GM-CSF)对接受免疫抑制治疗(IST)的重型再生障碍性贫血(SAA)患者的疗效和安全性。方法:使用相关检索词检索MEDLINE、Cochrane Library、EMBASE、CNKI及CBM数据库,检索时间1990年1月～2011年12月。纳入G-CSF或GM-CSF治疗SAA的随机对照研究。用Review Manager4.2统计软件对数据进行Meta分析。结果:共纳入4篇文献,共466例SAA患者。Meta分析结果显示:①IST疗效:G-CSF/GM-CSF组与对照组的SAA患者对比,近远期疗效与生存率均无显著差异:总体生存率[OR=1.15,95%C(I0.73,1.82),P=0.54]、完全缓解率[OR=1.20,95%CI(0.71,2.02),P=0.50]、早期总体有效率[OR=1.61,95%CI(0.85,3.03),P=0.14]、远期总体有效率[OR=1.17,95%CI(0.78,1.74),P=0.45];②IST相关感染:IST治疗早期感染发生率、严重感染发生率、感染相关死亡率方面均未优于对照组;③G-CSF/GM-CSF组的复发率低于对照组,差异显著[OR=0.57,95%C(I0.35,0.93),P=0.02];④G-CSF/GM-CSF组远期随访发生克隆性病变的发生率与对照组无统计学差异,恶性肿瘤(MDS/AML)发生率[OR=0.90,95%CI(0.41,1.99),P=0.79]、PNH发生率[OR=1.48,95%CI(0.65,3.33),P=0.35]。结论:G-CSF/GM-CSF应用于接受IST治疗的SAA患者,尚不能证明具有提高总体生存率、完全缓解率、总体有效率、减少感染和感染相关死亡率等优势。虽然有可能降低复发率,也不增加远期克隆性病变发生率,但还需要更严格设计的大样本双盲随机对照试验,并进行更为长期的随访研究。     

Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria

Recently, while studying erythrocytic apoptosis during Plasmodium yoelii infection, we observed an increase in the levels of non-parasitised red blood cell (nRBC) apoptosis, which could be related to malarial anaemia. Therefore, in the present study, we attempted to investigate whether nRBC apoptosis is associated with the peripheral RBC count, parasite load or immune response. To this end, BALB/c mice were infected with P. yoelii 17XL and nRBC apoptosis, number of peripheral RBCs, parasitaemia and plasmatic levels of cytokines, nitric oxide and anti-RBC antibodies were evaluated at the early and late stages of anaemia. The apoptosis of nRBCs increased at the late stage and was associated with parasitaemia, but not with the intensity of the immune response. The increased percentage of nRBC apoptosis that was observed when anaemia was accentuated was not related to a reduction in peripheral RBCs. We conclude that nRBC apoptosis in P. yoelii malaria appears to be induced in response to a high parasite load. Further studies on malaria models in which acute anaemia develops during low parasitaemia are needed to identify the potential pathogenic role of nRBC apoptosis.     

再生障碍性贫血中医药防治研究进展

再生障碍性贫血是由多种原因引起的骨髓造血功能衰竭,以全血细胞减少为特征的一种综合病症。目前普遍认为其发病机理与免疫因素介导的造血干细胞受损导致造血微环境异常相关。近年来,中医药以其独特的理论体系和治疗方法,在再生障碍性贫血的病因病机及防治防等研究方面取得了较大进展。中医药防治再生障碍性贫血一般从肾精亏虚、毒损髓络、生血乏源入手,以补肾填精、生血解毒为治疗法则,采用中药方剂或/和联合西药,可提高治疗有效率,降低西药的毒副作用,并可以调控T淋巴细胞的分化及相关细胞因子的表达。中药治疗可以改善骨髓造血微环境、不同程度的恢复骨髓的造血功能,提高患者的生存质量。现就中医药对此病的相关研究作一综述。     

Sea trout as a carrier of infectious salmon anaemia virus

Sea trout did not develop symptoms or gross clinical signs of infectious salmon anaemia (ISA) when injected with ascites from salmon, but ISA virus was propagated and haematocrit values dropped. The virus was transmitted from trout to salmon.     

Kinetics of the Hb A to Hb C switch and erythropoietin plasma levels in sheep

The induction of Hb A (alpha 2 beta A2) and Hb C (alpha 2 beta C2) synthesis in three adult sheep has been sequentially analysed, in relation to the reduction of the haematocrit (Ht) and to the changes of erythropoietin (Epo) concentration in plasma. Hb A production is detected in peripheral reticulocytes when the Ht approaches 70% of its initial value in correspondence with the first rise of EPO plasma level, whereas HB C synthesis appears when the Ht is further reduced to about 50%, at an Epo concentration two to three times higher. The assumption that the cell committed to HB C synthesis is close to the erythroid colony-forming unit (CFU-e) progenitor is also discussed.     

Validation of the use of phenylhydrazine hydrochloride (PHZ) for experimental manipulation of haematocrit and plasma haemoglobin in birds

The levels of haematocrit (Hct) and plasma haemoglobin (Hb) vary markedly through the annual cycle of birds, as well as among individuals at all life‐stages (embryos, chicks, adults). It is thus surprising that the functional, fitness‐related consequences of this variation are poorly understood. Putative ‘adaptive’ variation in these haematological traits has been associated with varying demands for aerobic capacity and oxygen transport, for example during migration, winter acclimatization, with increasing altitude, or during parental care. It has also been proposed that changes in Hct might reflect ‘costs’ of parental investment, for example during ‘reproductive anaemia’. However, almost all studies to date have been correlative. Here we describe a series of experiments that validate the use of phenylhydrazine hydrochloride (PHZ) for the transient, reversible experimental manipulation of Hct and Hb in birds. A single bolus injection (12.5 μg PHZ/g body weight delivered via intra‐muscular injection) caused a rapid decrease in Hct and plasma Hb within 24 h, from pretreatment values of 50–54% to 40–44% in non‐breeding Zebra Finches Taenipoygia guttata and European Starlings Sturnus vulgaris, and to 35% in breeding female Zebra Finches, changes within the normal physiological range. Hct and Hb returned to pre‐injection levels within 5–10 days of treatment. Changes in plasma Hb paralleled those for Hct. We suggest that PHZ treatment provides a widely applicable technique for use in experimental work to establish relationships between haematological status, aerobic capacity, workload (e.g. migration, parental care, thermoregulation), individual quality (of both adults and chicks) and trade‐offs such as costs of reproduction.