Cell viability of acute myeloid leukaemia blasts in culture correlates with treatment outcome

Despite the advances in understanding the pathophysiology of acute myeloid leukaemia (AML), the cure rate for acute myeloid leukaemia patients remains low. Cytogenetic abnormalities and age are the prognostic factors that guide treatment decisions. However, many AML patients still die. The biological factors that influence treatment outcome are largely unknown. Thus, the objective of our study was to use the in vitro viability test to correlate with treatment outcome. Acute myeloid leukaemia blasts demonstrated differing ability to survive in culture. Our examination of blast phenotype at various days in culture showed two possible growth directions. First, cells underwent maturation by increased expression of CD16 and down-regulated CD34 (a haemopoietic stem cell marker). These cells also appeared to have undergone apoptosis. Alternatively, cells continued to survive in culture and maintained high expression of CD34. An MTT assay was carried out to determine viability after three days of culture. Lower optical density values were obtained for samples that underwent apoptosis and higher values were obtained for samples that survived in culture. Apoptosis was measured by Annexin V/propidium iodide staining. A comparison between results of MTT assay and duration of disease free survival revealed that a higher viability in vitro correlated significantly with shorter survival duration in the patient (R -0.761, p=0.002, n=13). Thus, this study further supports the hypothesis that AML patients with poor survival may be related to having blasts with a biologically more immature or stem cell-like nature.     

Immunoglobulins in saliva of preterm and full‐term infants.

The aim of this longitudinal study was to determine salivary levels of total IgA, IgG and IgM in 84 preterm and 214 full‐term infants, from birth to 18 months of age. Unstimulated whole saliva was collected from each infant at birth, and subsequently at 3‐monthly intervals. Immunoglobulin levels were estimated using an ELISA technique. At birth, IgA was detected in 147/214 (69%) full‐term infants but only 47/84 (56%) preterm infants (P < 0.01). In the case of IgG, 61% of full‐term and 56% of preterm infants showed detectable levels, whereas IgM was found in 71% and 73%, respectively. Levels of IgA and IgG rose from birth to 18 months, whereas IgM levels did not change significantly. Increases in salivary levels of IgA were associated with introduction of solid foods (P < 0.001), as well as tooth eruption (P < 0.001). Our results indicate that the majority of full‐term and preterm infants are orally immunocompetent at birth.     

The use of dehydroepiandrosterone-treated rats is not a good animal model for the study of metabolic abnormalities in polycystic ovary syndrome

Objective

Hyperandrogenism is the hallmark of polycystic ovary syndrome (PCOS). The use of dehydroepiandrosterone (DHEA)-treated rats is thought to be a suitable animal model to study PCOS. In the present study, we assessed the severity of reproductive and metabolic abnormalities in DHEA-treated rats.

Lindane (γ‐Hexachlorocyclohexane) Induces Internal Ca2+ Release and Capacitative Ca2+ Entry in Madin‐Darby Canine Kidney Cells

The effect of lindane (γ‐hexachlorocyclohexane), an organochlorine pesticide, on Ca²⁺ mobilization in Madin‐Darby canine kidney cells was examined by fluorimetry using fura‐2 as a Ca²⁺ indicator. Lindane (5–200 μM) increased [Ca²⁺]_i concentration‐dependently. The [Ca²⁺]_i signal comprised an immediate initial rise followed by a persistent phase. Ca²⁺ removal inhibited the [Ca²⁺]_i signal by reducing both the initial rise and the sustained phase. This implies lindane‐triggered Ca²⁺ influx and Ca²⁺ release. In Ca²⁺‐free medium, 0.15 mM lindane increased [Ca²⁺]_i after pretreatment with carbonylcyanide m‐chlorophenylhydrazone (CCCP; 2 μM), a mitochondrial uncoupler, and two endoplasmic reticulum Ca²⁺ pump inhibitors, thapsigargin and cyclopiazonic acid. Conversely, pretreatment with lindane abolished CCCP‐ and thapsigargin‐induced Ca²⁺ release. This suggests that 0.15 mM lindane released Ca²⁺ from the endoplasmic reticulum, mitochondria and other stores. La³⁺ (1 mM) partly inhibited 0.1 mM lindane‐induced [Ca²⁺]_i increase, confirming that lindane induced Ca²⁺ influx. Addition of 3 mM Ca²⁺ increased [Ca²⁺]_i after pretreatment with 0.15 mM lindane for 750 sec. in Ca²⁺‐free medium, which indicates lindane‐induced capacitative Ca²⁺ entry. Lindane (0.15 mM)‐induced Ca²⁺ release was not reduced by inhibiting phospholipase C with 2 μM U73122, but was inhibited by 70% by the phospholipase A₂ inhibitor aristolochic acid (40 μM).     

B16细胞中FLT3表达的检测及FLT3-Ligand对B16细胞生长的抑制作用

目的：检测造血生长因子受体ＦＬＴ３ 在非造血来源的黑素瘤细胞系Ｂ１６ 中的表达,并研究其配基ＦＬＴ３－Ｌｉｇａｎｄ（ＦＬ）对Ｂ１６ 细胞的作用。方法：通过ＲＴ－ＰＣＲ检测Ｂ１６ 细胞中ＦＬＴ３ ｍ ＲＮＡ的表达,流式细胞仪检测ＦＬＴ３ 蛋白在Ｂ１６ 细胞表面的表达,在培养液中加入不同浓度的ＦＬ对Ｂ１６ 细胞进行培养。结果：ＦＬＴ３ 在Ｂ１６ 细胞中有ｍ ＲＮＡ 的表达,在Ｂ１６ 细胞表面有蛋白质的表达。ＦＬ对Ｂ１６ 细胞的生长有抑制作用,并且这种抑制作用是浓度依赖性的,在一定的浓度范围内随着ＦＬ浓度的增高而增强。结论：ＦＬＴ３ 的分布不仅仅局限于小鼠的造血系统和神经系统,也表达于上皮性的肿瘤细胞Ｂ１６ 中,并在其配基ＦＬ的作用下抑制Ｂ１６ 细胞的生长。     

Structural covariance networks of striatum subdivision in patients with Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel‐wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra‐striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato‐cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato‐cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices. Hum Brain Mapp 36:1567–1584, 2015. © 2014 Wiley Periodicals, Inc .     

人工全膝置换在严重膝内翻畸形患者中的应用

目的观察保留后交叉韧带人工全膝置换治疗严重膝内翻畸形患者的临床结果.方法回顾性分析1990年1月～1995年7月间严重膝内翻畸形骨关节炎患者(≥20°)人工全膝置换后的临床结果.假体为Miller-Galante-Ⅰ人工全膝(MG-Ⅰ,Zimmer公司).采用KSS评分对临床结果进行评估.结果38人56膝获完整随访,平均随访6(4～9)年.术前至最后一次随访,平均膝评分从33分提高到91分,其中84%优秀;平均膝关节功能评分自39增加到76分;两者的改善均有统计学意义(P＜0.01).86%的患者膝关节活动度超过90°,多数病例(50/56)术后膝关节力线正常,6例残留5～10°内翻畸形.总翻修率21%(12/56),平均翻修时间为术后5.5年.其它并发症包括髌骨半脱位,膝前痛,浅表感染.无深部感染、假体松动及前后向不稳.结论保留后交叉韧带人工全膝可矫正严重膝内翻畸形,术后内、外向不稳问题常致假体早期失败.     

我国造血干细胞基础研究的新进展兼论干细胞可塑性

1995年以来我国造血干细胞工程与相关的生物学领域的研究发展迅速。有关造血干 祖细胞基因表达的研究 ,上海国家人类基因组研究中心陈竺、陈赛娟等为正常和急性白血病人骨髓造血干祖细胞cDNA文库的基因表达建立了一套先进的工作体系。他们在许多白血病细胞系的干 祖细胞中发现了 30 0个新的相关基因。中山大学医学院李树浓、黄绍良等从人的桑葚期胚胎干细胞成功地诱导出造血细胞等。北京输血研究所裴雪涛等从成人和胎儿的骨髓分离出成年源干细胞 ,又进一步诱导分化为骨、软骨、脂肪和神经原细胞等。他们成功地构建了胎儿和成人间充质干细胞cDNA扣除文库 ,获得了胎儿和成人间充质干细胞的差异表达基因及在胎儿特异表达基因。中国医学科学院天津血液学研究所、国家血液学重点实验室赵春华等证实从胚胎胰腺、骨髓和肝脏中都可以分离出人间充质干细胞 ,又证明G CSF可以使输注的间充质干细胞在体内促造血重建。北京基础医学研究所毛宁等的实验不支持间充质干细胞可以“横向分化”。最近他们发现小鼠胚胎干细胞的体外分化重现了胚胎早期造血发生的生物学程序以及Smad5基因调控在胚胎造血发生中的必要性和多样性 ,又表明其上游配体TGF beta家族分子在胚胎发生中的作用和特点。本文针对干细胞可塑性研究作了评     

In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium

Background

Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A).

Objectives

We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk.

Methods

Using questionnaire data, we classified subjects as predominant solid-fuel users (e.g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center.

Results

Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49–1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73–6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06–1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups.

Conclusions

Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations.