用计算机程序进行Hardy—Wenberg氏平衡吻合度测验的方法

本文给出计算机程序进行Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ氏平衡吻合度的Ｘ＾２检验的方法和有关公式，同时给出在Ｘ＾２值和自由度ｎ给定的情况下，对概率Ｐ（Ｘ＾２，ｎ）进行精确计算的公式，这些方法和公式都已编成计算机程序，使得在进行Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ氏平衡吻合度测验时，能够对数据进行了自动化的统计分析，大大地提高了工作效率。     

成都地区汉族人群中FABP2和F13A1的遗传多态性

目的了解成都地区汉族群体中短串联重复序列ＦＡＢＰ２和Ｆ１３Ａ１的遗传多态性，获得ＦＡＢＰ２和Ｆ１３Ａ１两个基因座的群体遗传学数据。方法应用ＰＣＲ扩增技术结合聚丙烯酰胺凝胶水平电泳分型方法分别调查ＦＡＢＰ２和Ｆ１３Ａ１基因座在成都地区汉族群体中的基因型分布。结果ＦＡＢＰ２基因座在成都地区汉族群体中存在５个等位基因，基因频率分别为０．５１３，０．０９６，０．３３０，０．０５２，０．００９。杂合性为６０．８７％，基因型分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡。Ｆ１３Ａ１基因座在成都地区汉族群体中存在５个等位基因，基因频率分别为０．１２８，０．０５３，０．２８８，０．５２７，０．００４。杂合性６６．３７％，基因型分布不符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡，样本数据不能代表总体数据。结论ＦＡＢＰ２基因座的检测分型可用于法医学亲子鉴定与个人识别，Ｆ１３Ａ１基因座则不宜用于法医学亲子鉴定与个人识别。     

福州市汉族血员ABO血型基因频率调查

对福州市１２２７１名汉族献血员进行ＡＢＯ血型分布和基因频率调查，结果表明，福州市献血员的血型分布特点为Ｏ〉Ａ〉Ｂ〉ＡＢ，代表ＡＢＯ基因频率的ｐ、ｑ、ｒ分别为０．１７１８、０．１４０３和０．６８７６，观察值与Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡的差异不显著。     

复合PCR-RFLP技术检测ABO基因型

目的研究复合聚合酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）技术分型人类ＡＢＯ基因型。方法在每一个反应管内同时扩增ＡＢＯ糖基转移酶基因中２个特异性片段,然后于同一管内进行ＫｐｎⅠ和ＡｌｕⅠ限制酶消化,经聚丙烯酰胺凝胶电泳及银染,对武汉地区１２５例汉族无关个体作ＡＢＯ基因型分型。结果ＡＢＯ的６种基因型分型明确,１２５例汉族人ＡＢＯ基因型分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡。结论该方法操作简单,分型明确,重复性好,适用于法医学鉴定。     

成都地区汉族群体凝血因子ⅫA和B亚单位的遗传多态性研究

应用聚丙烯酰凝胶等电聚焦酶免疫检测技术，调查了成都地区汉族群体凝血因子Ⅻ和ＸＩＩＩＢ的遗传多态性，等一基因频率为：ＦＸＩＩＩＡ＊１＝０．８７１９，ＦＸＩＩＩＡ＊２＝０．１２４０，ＦＸＩＩＩＡ＊３＝０．００４１；ＦＸＩＩＩＢ＊１＝０．２７２７，ＦＸＩＩＩＢ＊２＝０．０１６５，ＦＸＩＩＩＢ＊３＝０．７１０７，ＦＸＩＩＩ表现型频率分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡定律。与国外其他群体的资料相比较，     

北京健康人群载脂蛋白B基因多态性及对血脂水平的影响

用聚合物链反应技术（ＰＣＲ）对北京地区２４６名无关汉族健康个体载脂蛋白Ｂ基因ＸｂａＩ位点限制性片段长度多态性进行测定及其对血清脂质，载脂蛋白水平的关系进行研究，结果表明：北京汉族健康人群以Ｘ－Ｘ－纯合子为主要基因型，占９５．１２％，Ｘ＋Ｘ－杂合型仅占４．８８％，未见Ｘ＋Ｘ＋基因型，经计算符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡定律，具有群体代表性；少见的Ｘ＋等位基因频率仅占０．０２４，显著低于欧美白种     

成都地区汉族群体凝血因子A和B亚单位的遗传多态性研究

应用聚丙烯酰胺凝胶等电聚焦酶免疫检测技术，调查了成都地区汉族群体凝血因子ＸⅢＡ和ＸⅢＢ的遗传多态性。等位基因频率为：Ｆ　Ａ＊１＝０．８７１９，Ｆ　Ａ＊２＝０．１２４０，Ｆ　Ａ＊３＝０．００４１；Ｆ　Ｂ＊１＝０．２７２７，Ｆ　Ｂ＊２＝０．０１６５，Ｆ　Ｂ＊３＝０．７１０７，Ｆ　表现型频率分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡定律。与国外其他群体的资料相比较，中国人Ｆ　Ａ＊１和Ｆ　Ｂ＊３等位基因频率相对较高。     

中国汉族群体c-Ha-ras基因3′端-VNTR位点遗传多态性的初步研究

为了探讨中国汉族ｃ－Ｈａ－ｒａｓ基因３′端ＶＮＴＲ位点遗传多态性，用ＡＦＬＰ－ＰＡＧＥ法对１１２例无亲缘关系的健康个体进行了ｃ－Ｈａ－ｒａｓ基因３′端ＶＮＴＲ位点分析，共检出２１个等位基因，其片段大小分布范围在６３５～２６５１ｂｐ之间，基因频率分布在０．００４５～０．５９３８。父权排除率（Ｐｅ）＝０．４４４５；杂合度（Ｈ）＝０．６２５；个体识别力（Ｄｐ）＝０．８４４０。共发现３４种基因型，经χ２检验（χ２＝２３７．１１，ｄｆ＝２１０，Ｐ＝０．１０２５），符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡。家系调查表明这一位点的等位基因按孟德尔规律遗传。本遗传标记系统在人类学、法医学和医学遗传学的研究中有重要意义。     

中国藏族群体TH01和VWA STR基因座的遗传多态性

目的了解中国藏族群体与汉族群体的遗传亲缘关系，获得藏族群体ＴＨ０１和ＶＷＡ基因座的群体遗传数据。方法ＥＤＴＡ抗凝血样采自８９名无血缘关系藏族个体，Ｃｈｅｌｅｘ法提取ＤＮＡ，ＰＣＲ扩增样本ＤＮＡ后，聚丙烯酰胺凝胶水平电泳分型。结果在西藏藏族群体中，ＴＨ０１基因座存在５个等位基因，等位基因频率为ＴＨ０１＊６：０．０９７、ＴＨ０１＊７：０．２２７、ＴＨ０１＊８：０．０９１、ＴＨ０１＊９：０．４８１及ＴＨ０１＊９．３：０．１０４，基因型分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡（χ２＝７．４２１ｄｆ＝８Ｐ＞０．０５）；ＶＷＡ基因座存在７个等位基因，等位基因频率为ＶＷＡ＊１４：０．１０１、ＶＷＡ＊１５：０．０３４、ＶＷＡ＊１６：０．２０８、ＶＷＡ＊１７：０．３０３、ＶＷＡ＊１８：０．２０８、ＶＷＡ＊１９：０．１２９及ＶＷＡ＊２０：０．０１７，基因型分布符合Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ平衡（χ２＝１９．６１ｄｆ＝１４Ｐ＞０．０５）；藏族和汉族的遗传距离为０．０３４，类似于欧洲群体间的遗传距离。结论西藏藏族两个ＳＴＲ基因座基因频率分布与汉族无显著差异，藏族与汉族在ＴＨ０１和ＶＷＡ基因座具有遗传同一性     

PCR法分析甲型血友病Ⅷ因子基因HindⅢ多态性位点检测携带者

目的探讨ＰＣＲ法对甲型血友病Ⅷ因子基因ＨｉｎｄⅢ多态性位点分析检测携带者。方法用ＰＣＲ扩增６个甲型血友病患者家系和２０７条无亲缘关系的Ｘ染色体的Ⅷ因子基因１９内含子，用ＨｉｎｄⅢ酶切进行Ａｍｐ－ＲＦＬＰｓ分析。结果查明ＨｉｎｄⅢ多态性位点频率为０．２９，根据Ｈａｒｄｙ－Ｗｅｉｎｂｅｒｇ定律计算妇女杂合子频率为０．４１，证明这个指数对检测甲型血友病携带者和进行产前诊断具有足够的信息量。研究的６个家系中有２个有信息（３３％）。结论为临床检测携带者和产前诊断提出有效的检测ＨｉｎｄⅢ多态性新途径     

General survey of intertumor linkages that connect the chronological changes of age-adjusted incidence rates of 13 neoplasia types from l975 to l993 in Japan

We attempted a stochastic study of cancer risk change in time using the follow-up data of the age-adjusted incidence rate (AAIR) of cancer in Japan, which covered 13 neoplasia types of both sexes in scope, and ranged from 1975 to 1993 in time. The purpose of our study was to test whether or not there was any mathematical regularity that was to condition cancer risk changes in time in all the 13 human neoplasia types. We investigated the relation between 2 neoplasias as regards log AAIR changes in time by the direct successive elimination method of Gauss, a fitness test of a given pair data to an equilibrium model. The fitness test was repeated in each of 156 tumor pairs [P(13.2)] in both sexes, in each of 3 (x, y) coordinates - the original (x, y) coordinates, the rect- (x, y) coordinates and the para- (x, y) coordinates. Total number of fitness test in this study was estimated to be 156x2x3=936. The rect- (x, y) coordinates and the para- (x, y) coordinates were defined each as an (x, y) framework with its x axis crossed at a right angle to the regression line of the original log AAIR data, and as another framework with its x axis run in parallel with the regression line of the original log AAIR data. The fitness of a given tumor to an equilibrium system was assessed in terms of the correlation coefficient value r within the range of -1.000 (the oncogene-type equilibrium system) to +1.000 (the tumor suppressor gene-type equilibrium system). Results obtained are given as follows: i) the positivity rates of the fitness test to the oncogene-type equilibrium system and the tumor suppressor gene-type system in the male all-cancer population were each 95.5% (149/156 tumor pairs) and 79.5% (124/156 tumor pairs), and those in the female all-cancer population were each 91.0% (142/156 tumor pairs) and 83.3% (130/156 tumor pairs). Evidence was available to indicate that all of the 13 human neoplasia types of both sexes was associated with both oncogene activation and tumor suppressor gene inactivation at the level of individual tumors. In other words, clearance of both oncogene activation and tumor suppressor gene inactivation was the sine qua non premise of carcinogenesis. ii) The positivity score profiles of a given tumor (profile-like presentation of positivity score for each tumor), for each of 2 cancer genes and for each sex, was highly specific for each of the 26 tumor units (13 tumors of both sexes). The presence of a highly specific positivity score pattern might be taken as another expression of complex interaction of 2 cancer genes in carcinogenesis. iii) Evidence was presented to suggest that specified interactions of the oncogene-tumor suppressor gene complexes of both sexes might be causally related to the emergence of sex discrimination of cancer risk, as testified in a set of tumors with both male dominance of cancer risk and female dominance of cancer risk. iv) The significance of one tumor pair that failed to show fitness to both the oncogene-type equilibrium system and the tumor suppressor gene-type equilibrium system was discussed in terms of spacially restricted dissociation of the power center of the oncogene-type equilibrium system from that of the tumor suppressor gene-type equilibrium system in a given tumor pair.     

Magnitude of serum and intestinal antibody responses induced by sequential replicating and nonreplicating rotavirus vaccines in gnotobiotic pigs and correlation with protection

A sequential mucosal prime-boost vaccine regimen of oral attenuated (Att) human rotavirus (HRV) priming followed by intranasal (i.n.) boosting with rotavirus protein VP2 and VP6 rotavirus-like particles (2/6-VLPs) has previously been shown to be effective for induction of intestinal antibody-secreting cell (ASC) responses and protection in gnotobiotic pigs. Because serum or fecal antibody titers, but not intestinal ASC responses, can be used as potential markers of protective immunity in clinical vaccine trials, we determined the serum and intestinal antibody responses to this prime-boost rotavirus vaccine regimen and the correlations with protection. Gnotobiotic pigs were vaccinated with one of the two sequential vaccines: AttHRV orally preceding 2/6-VLP (VLP2x) vaccination (AttHRV/VLP2x) or following VLP2x vaccination (VLP2x/AttHRV) given i.n. with a mutant Escherichia coli heat-labile toxin (mLT) as adjuvant. These vaccines were also compared with three i.n. doses of VLP+mLT (VLP3x) and one and three oral doses of AttHRV (AttHRV1x and AttHRV3x, respectively). Before challenge all pigs in the AttHRV/VLP2x group seroconverted to positivity for serum immunoglobulin A (IgA) antibodies. The pigs in this group also had significantly higher (P < 0.05) intestinal IgA antibody titers pre- and postchallenge and IgG antibody titers postchallenge compared to those in the other groups. Statistical analyses of the correlations between serum IgM, IgA, IgG, and virus-neutralizing antibody titers and protection demonstrated that each of these was an indicator of protective immunity induced by the AttHRV3x and the AttHRV/VLP2x regimens. However, only IgA and not IgM or IgG antibody titers in serum were highly correlated (R2 = 0.89; P < 0.001) with the corresponding isotype antibody (IgA) titers in the intestines among all the vaccinated groups, indicating that the IgA antibody titer is probably the most reliable indicator of protection.     

Light and electron radiation fields' coincidence at extended distance

Light field is routinely used for matching electron fields with adjacent photon fields and also positioning an ion chamber for cutout output measurements. At extended distance, however, the peripheral aspects of a radiation field are shifted with respect to their light shadow by up to 10 mm at SSD of 115 cm. This is mostly due to a difference in positions of light and virtual electron sources; however loss of the lateral scatter equilibrium, electron scatter in air, and partial transmission through cutout edges can also contribute to the effect. For the aperture sizes large enough for the lateral scatter equilibrium to be achieved, a simple geometrical formula allows one to calculate the misalignment at off-axis locations if the virtual electron source position is known. If the source position is not known or the aperture is too small for the lateral scatter equilibrium to be established, then a light-radiation coincidence test using a ready-pack film at dmax can be used to measure the light and electron radiation fields coincidence.     

Neurotropism in newborn hamsters of plaque purified measles virus clones

Summary Three plaque purified measles virus clones displayed a different neurotropism in newborn hamsters.The coincidence was emphasized and discussed of the highest neurovirulence exhibited by one of the clones with the property of manifestingin vitro syncytia formation, slow viral release and thermolability.This investigation was supported by the Consiglio Nazionale delle Ricerche, Grant No. 73.01400.44.     

Recombinant human thrombopoietin augments mobilization of peripheral blood progenitor cells for autologous transplantation.

This study assessed the ability of various schedules of recombinant human thrombopoietin (rhTPO) to enhance mobilization of peripheral blood progenitor cells (PBPCs) in 134 patients with cancer undergoing high-dose chemotherapy and autologous PBPC transplantation. Patients received the study drug on days 1, 3, and 5 before initiation of granulocyte colony-stimulating factor (G-CSF) 10 microg/kg/day on day 5 and pheresis starting on day 9. Randomly assigned treatments on days 1, 3, and 5 were: group 1 (n=27) placebo, placebo, rhTPO 1.5 microg/kg; group 2 (n=27) rhTPO 1.5 microg/kg, placebo, placebo; groups 3 (n=28) and 4 (n=22) rhTPO 0.5 microg/kg on all 3 treatment days; and group 5 (n=30) placebo on all 3 treatment days. After high-dose chemotherapy and PBPC transplantation, groups 1 through 4 received rhTPO 1.5 microg/kg days 0, +2, +4, and +6 with either G-CSF 5 microg/kg/day (groups 1-3) or granulocyte-macrophage colony-stimulating factor 250 microg/m(2)/day (group 4). Group 5 received placebo plus G-CSF 5 microg/kg/day. The addition of rhTPO to G-CSF increased median CD34+ cell yield/pheresis in cohorts in which rhTPO was started before day 5, with higher yields in groups 2 (2.67 x 10(6)/kg) and groups 3 and 4 (3.10 x 10(6)/kg) than in group 1 (1.86 x 10(6)/kg) or group 5 (1.65 x 10(6)/kg) (P=.006 across groups). Comparing rhTPO to placebo, higher percentages of patients achieved the minimum yield of CD34+ > or =2 x 10(6)/kg (92% v 75%; P=.050) as well as the target yield of CD34+ > or =5 x 10(6)/kg (73% v 46%; P= .041). rhTPO-treated patients required fewer phereses to achieve minimum (P= .011) and target (P= .015) CD34+ cell values. rhTPO given after transplantation did not speed platelet recovery. No neutralizing antibodies were observed. We conclude that rhTPO can safely enhance mobilization of PBPC, reduce the number of leukapheresis, and allow more patients to meet minimal cell yield requirements to receive high-dose chemotherapy with PBPC transplantation.     

An optimized strategy for choosing the number of platelet concentrates to pool.

CONTEXT: The number of platelet concentrates (PCs) pooled per dose varies widely. The number should be based on quality control statistics. OBJECTIVE: To determine the optimal number of PCs per pool that will achieve a target dose. DESIGN: The population statistics of PC cell counts were obtained from routine quality control records. A target value of 3.00x10(11) cells was chosen. A theoretical model to predict the probability of achieving this target cell count was developed. MAIN OUTCOME MEASURES: The calculated probability was tested in a Monte Carlo simulation. RESULTS: The mean of a sequential series of 100 PC counts (obtained from routine quality control records) was 9.08x10(10), and the standard deviation was 2.70x10(10). Platelet loss during pooling was measured at 8.3%, so that the pooling of 3.27x10(11) cells is required to deliver a dose of 3.00x10(11) cells. The pooling of 4 PCs from this data set predicts an average pool cell count of 3.63+/-2.30x10(11). Using standard tables for normal distribution, the probability of achieving a minimal pool dose of 3.00x10(11) cells is estimated to be greater than 0.76. Similarly, the probability of achieving the target value by pooling 5 PCs is greater than 0.99. In a Monte Carlo simulation selecting 4 PCs, 76.5% of the trials were successful, and for 5 PCs, 99.5% were successful (estimated P values of .77 and .99, respectively). CONCLUSION: Five PCs per pool are necessary and sufficient to achieve the chosen target value given the cell count characteristics of our PC supply.     

Estimation of baroreflex gain using a baroreflex equilibrium diagram

Two types of closed-loop perturbations can be applied to the arterial baroreflex system. The first (P(D1)) is introduced into the baroreceptors without a direct effect on arterial pressure (AP), whereas the second (P(D2)) initially affects AP. Neck suction and hemorrhage are examples of P(D1) and P(D2), respectively. To estimate the baroreflex open-loop gain (G(Baro)) without knowing the absolute magnitudes of P(D1) and P(D2), we explored a new strategy to estimate G(Baro) by combining P(D1) and P(D2) in a baroreflex equilibrium diagram. In this diagram, the neural arc presents the input-output relationship between baroreceptor pressure input and sympathetic nerve activity (SNA). The peripheral arc presents the input-output relationship between SNA and AP. In 8 anesthetized rabbits, we estimated G(Baro) by multiplying the slopes of the peripheral arc determined from P(D1) and the neural arc determined from P(D2). We also estimated G(Baro) by a conventional open-loop analysis. The G(Baro) values estimated by the equilibrium diagram and the open-loop analysis showed a positive correlation (y = 0.80x + 0.22, r(2) = 0.95) and a standard error of estimate of 0.21 across the animals. We conclude that G(Baro) was estimated well by combining P(D1) and P(D2) in the equilibrium diagram.     

染色体22q11微缺失综合征的临床表现与荧光原位杂交诊断结果

目的研究22q11微缺失综合征（22q11 microdeletion syndrome,22q11 DS）的临床特征与荧光原位杂交技术（fluorescencein situhybridization,FISH）诊断结果的意义。方法评估临床表型,应用FISH技术检测外周血标本22q11区域的微缺失;对FISH结果和临床特征进行多因素Logistic回归分析。结果64例疑似患儿中FISH检测微缺失为14例,阳性率21.9%。确诊患儿广泛存在多发畸形。建立了以面容异常（x1）、先天性心脏畸形（x2）、免疫问题（x3）为变量的FISH诊断结果（y）的Logistic回归预测方程：y=-8.206＋2.324x1＋2.725x2＋1.674x3,P=exp（y）/[1＋exp（y）]。结论精确的临床评估可以初次筛选有22q11微缺失危险性的患儿,其FISH检查结果可通过Logistic回归方程进行预测。     

两种不同检测系统测定血清降钙素原的比较实验研究

目的 探讨三联生物微阵列化学发光检测系统测定血清降钙素原（PCT）结果的可靠性。方法 以罗氏Cobas e 601电化学发光检测系统为参照系统,三联生物微阵列化学发光检测系统为待评估系统,对血清PCT浓度进行测定并进行统计分析。结果罗氏电化学发光检测系统血清 PCT日内精密度的变异系数（CV）为5.33%~7.88%,日间CV为5.62%~8.56%。三联生物微阵列化学发光检测系统的日内CV为4.93%~7.28%,日间CV为5.47%~8.90%。两种检测系统有较好的相关性（回归方程y=1.174x+0.213,P＜0.05）,相关系数r2为0.997。在医学决定水平（PCT为0.50 ng/ml和2.0 ng/ml）处的Kappa值分别为0.878（P=4.60×10-7）和0.933（P=7.72×10-8）,阳性符合率分别为94.44%和100.00%,阴性符合率分别为93.33%和95.45%。结论 三联生物微阵列化学发光免疫分析法与罗氏电化学发光法测定血清PCT结果相关性和一致性好,可用于临床血清PCT的快速检测。     

Off-rate and concentration diversity in multidonor-derived dimers of immunoglobulin G

IgG-dimers in multidonor-derived preparations of IgG antibodies represent not only agents of therapeutic potential, but also molecules of basic immunological interest since their composition mirrors the currently unknown range of clonal concentrations and affinities. To analyze this fundamental type of diversity, a computational model is developed in agreement with a density functional theory and used to simulate the dissociation kinetics of dimers separated from a 5000 donor-derived IgG preparation (protein concentration: 0.74 mg/mL) via superimposition of 8100 arbitrary combinations of off-rates and initial concentrations. The Greedy algorithm-like procedure described requires iterative and consecutive changes of 8 from a total of 11 fitting parameters and allows to approximate the probability density distributions of either quantities within defined limits (apparent off-rates: approximately 4 x 10(-4) to 9 x 10(-17)s(-1); concentrations: approximately 3 x 10(-20) to 1 x 10(-11)M) by lognormal distributions of log-log(10)-type, each of them adapted with four particular parameters, as well as the number of different dimer populations ( approximately 2 x 10(13)). Moreover, reasonably dimensioned equilibrium constants involved in monovalent and bivalent random IgG dimerization are estimated by using a mean on-rate of 2.5 x 10(5)M(-1)s(-1) and interrelationships of molecular parameters derived from known models for antibody-antigen interaction.