初诊急性髓系白血病患者FLT3-ITD和NPM1基因联合突变与临床特征的关系

目的探讨初发急性髓系白血病（AML）患者中FMS样酪氨酸激酶3-基因内部串联重复（FLT3-ITD）和核仁磷酸蛋白1（NPM1）基因突变的发生频率,并进一步分析其与患者临床特征的关系。方法收集44例临床初诊为AML的成人患者骨髓标本,通过基因组DNA-PCR技术对FLT3-ITD和NPM1基因突变进行检测。结果44例患者共检测到FLT3-ITD突变10例,检出率22.7%。FLT3-ITD突变阳性的10例患者和无突变者初诊WBC中位数分别为（98.5±22.5）×109/L和（42.9±12.4）×109/L,两者相比具有统计学差异（P＜0.05）。44例患者共检测到NPM1突变14例,检出率31.8%。大部分突变患者,染色体核型正常。结论FLT3-ITD和NPM1基因突变是AML患者中常见的分子生物学异常,对患者的临床和预后有影响。     

非小细胞肺癌EGFR基因第一内含子（CA）n多态性与基因突变及预后的关系

目的研究非小细胞肺癌（NSCLC）患者表皮生长因子受体（EGFR）基因第一内含子（CA）n[intron 1（CA）n]多态性与EGFR基因突变的关系,并观察患者的预后。方法观察129例NSCLC患者生存情况,检测患者手术切除新鲜癌组织或石蜡包埋组织EGFR基因intron 1（CA）n及19、21外显子突变。结果129例NSCLC患者中,检出EGFR基因突变35例（27.1%）,其中EGFR19外显子21例（16.3%）,21外显子15例（11.6%）。EGFR intron 1（CA）n出现频率最多的等位基因为（CA）20（38.8%）,其次为（CA）16（26.4%）。短（CA）n与EGFR基因突变有关,特别是19外显子突变,差异有统计学意义（均P＜0.05）,但与21外显子突变无明显相关,差异无统计学意义（P＞0.05）。（CA）16与19外显子突变有关,差异有统计学意义（P＜0.05）。EGFR基因intron 1短（CA）n与长（CA）n NSCLC患者总生存时间差异无统计学意义（P＞0.05）。结论 EGFR第一内含子短（CA）n,特别是（CA）16重复序列可能是影响19外显子缺失突变的一个重要因素。（CA）n多态性不是NSCLC患者预后的危险因素（P＞0.05）。     

先天性白内障一家系的致病基因研究

目的 对一个来自浙江省杭州地区的三代先天性白内障家系进行常染色体显性遗传基因的突变分析,以寻找其可能的致病基因及突变位点。方法 该家系共10例成员,其中包括4例患者。10 例家系成员在浙江省人民医院眼科中心接受眼科专科检查及全身检查,以排除存在白内障以外的眼部及全身疾患。10例家系成员各抽取外周血5ml,提取基因组DNA。针对国内外文献报道的与常染色体显性遗传先天性白内障相关的18 个基因（CRYAA、CRYAB、CRYBA1、CRYBA2、CRYBA4、CRYBB1、CRYBB2、CRYGC、CRYGD、CRYGS、GJA3、GJA8、MIP、BFSP、HSF4、PITX3、EPHA2、PAX6）设计引物,进行PCR 扩增,对扩产物进行测序和序列分析,了解这10例家系成员的以上基因是否存在相应的序列。结果 临床眼科检查显示该家系先天性白内障类型为粉尘状白内障。候选基因序列测定显示在CRYAA 第1 个外显子中第6 位碱基发生C→T 置换,氨基酸同为天门冬氨酸。该家系中所有患者均有此改变,而所有的正常家系成员均无此改变。结论 CRYAA 第1个外显子中第6位碱基发生C→T的同义突变可能是导致该家系先天性白内障发生的致病原因。     

膀胱移行细胞癌患者人类白细胞抗原G的表达及其与临床病理学特征的相关性

目的探讨膀胱移行细胞癌组织中人类白细胞抗原G （HLA- G）的表达及其与临床病理特征的关系。方法选取62例膀胱移行细胞癌手术切除标本组织，另取术中癌旁正常膀胱黏膜组织标本作为对照，采用免疫组织化学Envision方法检测两种组织中HLA- G的表达情况，并分析其与临床病理特征的关系。结果62例膀胱移行细胞癌患者中43例（69.4%）HLA- G阳性表达，20例癌旁正常膀胱黏膜组织中均未见HLA- G阳性表达。HLA- G的表达水平与膀胱移行细胞癌患者性别、年龄、肿瘤数目、临床分期、组织学分级均无明显相关性（均P＞0.05）。结论膀胱移行细胞癌组织中HLA- G表达上调，HLA- G高表达与膀胱移行细胞临床病理特征无关。     

支气管哮喘患者白三烯受体1基因MicroRNA的表达

目的探讨支气管哮喘患者外周血细胞白三烯受体-1（CysLTR1）基因MicroRNA的表达及临床意义。方法选择支气管哮喘急性发作患者17例（哮喘发作组）、支气管哮喘诊断明确且临床症状完全缓解3个月以上患者15例（哮喘缓解组）和健康体检者20例（正常对照组）,采用RT-PCR技术检测外周血细胞CysLTR1基因MicroRNA的表达,并比较分析3组检测结果。结果CysLTR1基因MicroRNA在正常对照人群和支气管哮喘患者中均有表达,但表达水平不同：哮喘发作组、哮喘缓解组和正常对照组CysLTR1/GAPDH分别为2.4059±0.1983、2.1800±0.2210和1.2300±0.1174,与正常对照组相比,哮喘发作组和哮喘缓解组CysLTR1基因MicroRNA的表达均明显增高（均P＜0.05）;哮喘发作组与哮喘缓解组比较,差异无统计学意义（P＞0.05）。结论哮喘患者CysLTR1基因MicroRNA高表达可能与哮喘发生或急性发作相关。     

FasL基因-844T/C单核苷酸多态性与浙江地区食管鳞癌易感性关系的研究

目的：研究FasL基因启动子区-844T/C单核苷酸多态性（SNP）与食管鳞癌易感性的关系。方法提取248例食管鳞癌患者（患者组）和297例健康体检者（对照组）外周血基因组DNA，以PCR-RFLP检测FasL-844T/CSNP。分析、比较两组该位点SNP的表达差异。结果食管鳞癌患者与健康体检者的FasL基因启动子区-844位点基因型分布差异有统计学意义（P＜0.01）。以TT基因型为对照，TC基因型不增加食管鳞癌患病风险（P＞0.05），而CC基因型则显著减少食管鳞癌患病风险（调整后OR=0.425，95%CI=0.255-0.708，P＜0.01）。以T等位基因为对照，C等位基因显著减少食管鳞癌患病风险（调整后OR=0.597，95%CI=0.460-0.776，P＜0.01）。结论在浙江地区人群中FasL基因-844T/CSNP与食管鳞癌的易感性有关。     

肥大细胞在人乳头瘤病毒感染导致宫颈鳞癌发生发展中的作用研究

目的观察人乳头瘤病毒（HPV）和肥大细胞（MC）在正常宫颈组织、宫颈上皮内瘤变（CIN）及宫颈鳞癌（SCC）组织中的表达。方法采用S—P免疫组化法检测60例CIN患者、40例SCC组患者和20例子宫肌瘤患者（对照组）组织中MC的表达，同时采用DNA导流杂交基因芯片技术检测各级组织脱落细胞中HPVDNA分型。结果随着宫颈病变程度的加重．高危型（HR）-HPV感染阳性率逐渐增加，分别为10％、55％、65％、85％、100％，其中最常见的高危型HPV感染的基因型为：16、58、52、18。与CINIII组比较，MC密度在CIN11组、SCC组、对照组中的表达明显升高（P〈0．01或0．05），并且MC与肿瘤临床分期和血管转移有关（均P〈0．05）。MC低表达者与高表达者间HR—HPV阳性率的差异有统计学意义（P〈0．01）。结论HR—HPV感染可以降低MC的表达，癌组织中浸润的MC可以促进肿瘤血管的形成和肿瘤的浸润转移。     

子痫前期患者CD4+CD25+调节 性T细胞亚群的改变及意义

目的 探讨子痫前期患者CD4+CD25+调节性T细胞（Treg）亚群改变及在PE免疫耐受失衡中的作用。方法 选 取PE 患者（观察组）30 例,同期正常晚期妊娠（对照组）20 例。分别采集PE 患者和正常晚期妊娠妇女外周血,采用流式细胞术检测Treg 以及活化记性相关（CD45RO、HLA-DR）、归巢相关（CCR4、CCR6、CD103）、功能相关（ICOS、CTLA-4、Galectin 1）和生存相关（PD1 和CD95）标记分子的表达。采用免疫抑制实验检测外周血中Treg 的免疫抑制功能。结果 观察组患者外周血CD4+CD25+细胞的比例[(5.87±3.34) %]低于对照组[（6.65±1.18）%],但差异无统计学意义。免疫抑制实验显示观察组患者外周血中Treg 对CD4+CD25-T 细胞的增值抑制作用与对照组无统计学差异。通过对Treg 多个标记分子的检测进一步发现,ICOS 和CCR6 在观察组Treg 上的表达水平显著低于对照组Treg（均P＜0.01）;CCR4 和Galectin 1的表达水平较对照组低,而CD45RO、HLA-DR 、CD103、CTLA、PD1 和CD95 的表达水平较对照组高,但两组间差异均无统计学意义（均P＞0.05）。结论 Treg 亚群比例失调可能是导致子痫前期发生的重要因素。     

早期自然流产患者绒毛滋养细胞中CXCL14的表达及其临床意义

目的研究正常早孕妇女和早期自然流产妇女之间绒毛滋养细胞中CXCL14的表达情况，探讨其表达的临床意义。方法选取33例正常早孕妇女绒毛组织和37例早期自然流产妇女绒毛组织，HE染色后光镜下观察两组绒毛组织的形态学变化；采用免疫组化SP三步法检测两组绒毛滋养细胞中CXCL14的表达。结果HE染色下两组绒毛滋养细胞形态对比，见早期自然流产组绒毛组织滋养细胞层变薄、滋养细胞变性甚至坏死、滋养细胞嗜酸性增强、绒毛间质水肿坏死；免疫组化示正常早孕组绒毛滋养细胞CXCL14的表达量为0.07±0.05，自然流产组绒毛滋养细胞CXCL14的表达量为0.12±0.02，两组比较差异具有统计学意义（P＜0.01）；首次流产组CXCL14表达量0.116±0.067，多次流产组CXCL14表达量0.086±0.127，两组比较差异无统计学意义（P＞0.01）。结论早期自然流产绒毛滋养细胞中CXCL14表达升高，可能在自然流产的发生中起着重要作用。     

急性脑梗死患者脑微出血的发病情况及其危险因素分析

目的探讨急性脑梗死患者脑微出血的发病情况及其危险因素。方法选择急性脑梗死患者75例,男51例,女24例,年龄42～83（64.9±10.8）岁。行头颅CT、磁敏感成像（SWI）检查,依据脑微出血检出的结果分成阳性组（23例）与阴性组（52例）,比较两组的一般资料,探讨脑微出血发病的危险因素。结果SWI检查的检出率比CT检出率高（χ2=27.17,P＜0.05）。阳性组年龄、高血压病、糖尿病患病率均较阴性组高,差异均有统计学意义（均P＜0.05）;两组性别、血脂异常、心房颤动、冠心病、吸烟、饮酒情况比较,差异均无统计学意义（均P＞0.05）。logistic回归分析显示年龄增长、高血压病是脑微出血的独立危险因素（P＜0.05）。结论急性脑梗死患者合并存在脑微出血的比例高,SWI检查是检测脑微出血的敏感方法,年龄大、高血压病与脑微出血的发生密切相关。     

Long-term dynamics of chromosomal instability in cancer: A transition probability model

A stochastic model of chromosomal instability has been previously developed which has included one adjustable parameter—the probability of a segregation error. Using computer simulations, we have previously analyzed this model and were able to reproduce a short-term dynamics of chromosome copy number distributions in clones of cancer cells. In a short run, segregation errors provide a continuous production of deviant cells with increasing variation of cell karyotypes, which depends upon the rate of segregation errors. In the long-term observations, many tumors and cancer cell lines have been observed to maintain a stable, although abnormal, distribution of chromosome number for hundreds of cell generations. This phenomenon of “stability within instability” presents an interesting paradox, which could be addressed mathematically. However, this would require modeling of long term growth of tumor cell clones for hundreds of generations, which has far exceeded capabilities of modern computer systems. In this study, we have analyzed asymptotic behavior of our model using a semianalytical approach. A transition probability matrix was derived analytically and implemented in a recursive algorithm for computational experiments. Using this transition probability model, the expected frequencies of chromosome copy number have been calculated under various initial and boundary conditions. We have also tested several alternative models, which describe various mechanisms of errors in segregation of chromosomes, and found conditions for stabilization of distribution of chromosomes copy numbers over a large number of cell generations. Stable clonal frequencies were estimated which are independent of initial conditions, i.e., chromosome copy numbers in the initiator cells. These stable distributions were, however, dependent on the model assumptions regarding particular mechanism of errors in segregation of chromosomes. Thus, our modeling results have suggested a possible connection between the form of stable distribution of chromosome numbers in tumors and the underlying mechanism of errors in segregation of chromosomes. This new analytical approach allows us to overcome technical impairments and limitations of computer simulation, and, for the first time, provides mathematical insight into long-term evolution of chromosome numerical changes in human tumors.     

Modeling the optimal ethnic composition of an adult stem cell registry

For patients suffering from a blood related disease, a stem cell transplant represents the best, and sometimes the only, possible treatment. Registries have been created throughout the world to match patients with stem cell donors. Canada's adult registry, OneMatch, was formed to meet the needs of Canadian patients. However, only 20–30 percent of unrelated adult stem cell transplants in Canada are sourced from Canadian donors. Self-sufficiency has proven difficult for OneMatch, in part, because the Canadian registry is dwarfed by other international registries with similar donor populations.In this paper, we present a study to evaluate changes the Canadian registry designed to promote ethnic diversity while meeting the needs of the Canadian patient population. We formulate the composition problem as a linear optimization model and solve it using a combination of exact and heuristic methods for a registry of 1 M donors.We conclude that when registry size is constrained, there are advantages to increasing ethnic diversity over self-sufficiency. However, results show that some communities cannot be easily accommodated within an adult registry of a fixed size. Thus, our results highlight the need for stem cells derived from cord blood for hard to match populations.     

Separately continuous functions on products of locally convex spaces with the weak topology

We study the inverse problem of the theory of separately continuous functions, that is, the problem of constructing a separately continuous function with a prescribed set of points of discontinuity. It is shown that for a given F-set C in the product X×Y of two spaces X and Y in the class of compatible spaces, which includes in particular metrizable spaces and semireflexive locally convex spaces in the weak topology with a metrizable separable dual embedded in the product A×B of the sets AX and BY of first category in X and Y respectively, there exists a separately continuous function f. X×Y whose set of points of discontinuity is C.Translated fromMatematichni Metodi ta Fiziko-Mekhanichni Polya, Vol. 40, No. 3, 1997, pp. 25–30.     

Characterizations of normal, hyponormal and EP operators

In this paper normal and hyponormal operators with closed ranges, as well as EP operators, are characterized in arbitrary Hilbert spaces. All characterizations involve generalized inverses. Thus, recent results of S. Cheng and Y. Tian [S. Cheng, Y. Tian, Two sets of new characterizations for normal and EP matrices, Linear Algebra Appl. 375 (2003) 181-195] are extended to infinite-dimensional settings.     

Analyzing students’ communication and representation of mathematical fluency during group tasks

Findings discussed in this paper are from a larger research project exploring mathematical fluency characteristics, and teacher noticing and interpreting of mathematical fluency. The current study involved students from seven primary classes (Kindergarten – Grade 6, N = 63 students) and investigated students’ written work samples and oral discussions as they collaborated in small groups to solve mathematical tasks. Students displayed mathematical fluency both orally and in written/drawn form. Certain aspects of mathematical fluency were easier to identify orally (adaptive reasoning) particularly for younger students and when students did not provide any written reasoning. Analyzing the oral responses was often needed to identify mathematical fluency beyond knowledge of a correct procedure (strategic competence). Findings suggested that the various representations students used were valuable for observing mathematical fluency. These results suggest that oral assessments as a means to understand and interpret students’ mathematical fluency are necessary.     

Dynamics and numerical simulations in a production and development of red blood cells model with one delay

In this paper, we study an unstructured model of a cellular population in the spirit of Grabosch and Heijmans [Grabosch A, Heijmans HJAM. Production, development and maturation of red blood cells, A mathematical model. AM-R 8919, ISSN 0924-2953, 1989.] model. The cellular population is described by a system of differential equations with one delay. The basic assumption is that the cell population responsible for the production of blood cells consists of three compartments: the stem cells, the precursor cells, and the blood cells. We prove that the model has two possible steady states and their dynamics (depending on time delay) are studied in term of the local stability, we illustrate these results with numerical simulations for some different values of the time delay.     

Holomorphic maps of generalized Iwasawa manifolds

Let G₁, G₂ be complex Lie groups with . Suppose that : G₁G₂ is a holomorphic map which takes the identity to the identity. Then is a homomorphism of groups. In this paper we give an example of the above type of result in the category of homogeneous spaces. In particular we prove that every normalized holomorphic map : XY from a generalized Iwasawa manifold X to a complex manifold Y=G/H, where G is nilpotent and H is discrete, is liftable to a unique group homomorphism. The assumption of discrete isotropy for the range space is essential. Our result follows from a criterion for holomorphic mappings between upper-triangular matrix groups being polynomial.Partially supported by NSF grant No. 2660-11833-942008     

Numerical Simulation of Red Blood Cell Suspensions Behind a Moving Interface in a Capillary

Computational modeling and simulation are presented on the motion of red blood cells behind a moving interface in a capillary. The methodology is based on an immersed boundary method and the skeleton structure of the red blood cell (RBC) membrane is modeled as a spring network. As by the nature of the problem, the computational domain is moving with either a designated RBC or an interface in an infinitely long two-dimensional channel with an undisturbed flow field in front of the computational domain. The tanking-treading and the inclination angle of a cell in a simple shear flow are briefly discussed for the validation purpose. We then present and discuss the results of the motion of red blood cells behind a moving interface in a capillary, which show that the RBCs with higher velocity than the interface speed form a concentrated slug behind the moving interface.     

Modelling hematopoiesis in health and disease

Hematopoiesis is the process responsible for maintaining the number of circulating blood cells that are undergoing continuous turnover. At the root of this process are the hematopoietic stem cells (HSC), that replicate slowly to self-renew and give rise to progeny cells that proceed along the path of differentiation. The process is complex, with the cells responding to a wide variety of cytokines and growth factors. We discuss the mathematics of hematopoiesis based on stochastic cell behavior. Multiple compartments are introduced to keep track of each cell division process and increasing differentiation. The same mathematical model that describes normal hematopoiesis across mammals as a stable steady state of a hierarchical stochastic process is also used to understand the detailed dynamics of various disorders both in humans and in animal models. The microecology of the multitude of cell lineages that constitute what we call troubled hematopoiesis evolves in time under mutation and selection, the paradigmatic components of Darwinian evolution. Thus, the present approach provides a novel perspective for looking at cancer progression and cure.