Comparison of Marker Intervals and Number of Sib Pairs Used for Linkage Analysis on Simulated Nuclear Family Data

Using a two‐stage global scan design, we analyzed general population replicates 1 and 42 of the Genetic Analysis Workshop (GAW) 12 simulated data set using three methods: revisited Haseman‐Elston (HER), maximum likelihood variance estimation (ML), and variance components (VC). Three marker densities, 5‐, 10‐, and 15‐cM intervals, were examined in the first‐stage scan. We found that the 10‐cM interval appears to be the most cost‐effective approach in genotyping without sacrificing power when using a first stage significance level of 0.01. Subsequently, we performed the second‐stage scan at 1‐cM intervals for those putative positive regions identified in the first‐stage scan at a significance level of 0.01. We also compared the power to detect linkage using different numbers of sib pairs for a genome‐wide scan at a 10‐cM interval and found that power decreases nonlinearly as the number of sib pairs decreases. © 2001 Wiley‐Liss, Inc.     

Importance of an immunodominant surface-exposed loop on outer membrane protein P2 of nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHI) frequently causes recurrent infections of the respiratory tract in humans. Previous indirect evidence suggested that a strain-specific immune response occurs following infection and that this immune response is directed at an immunodominant epitope on the bacterial surface. To test this hypothesis, mice and rabbits were immunized with whole cells of a strain of NTHI and the antiserum was characterized to identify the antigens to which antibodies were directed. All animals made a prominent antibody response to the loop 5 region of the P2 molecule, which is the major outer membrane protein. Rabbit serum showed complement-dependent bactericidal activity. Adsorption of the immune serum with the loop 5 fusion peptide removed bactericidal activity and also abolished reactivity to P2 detected by an immunoblot assay, an enzyme-linked immunosorbent assay, and a radioimmunoprecipitation assay. These data indicate that immunization with whole cells of NTHI results in a prominent antibody response which is directed at epitopes on the loop 5 region of the P2 molecule. Thus, a strain-specific immune response to NTHI occurs as a result of the expression of an immunodominant epitope on the P2 molecule.     

牙源性脓肿标本中的产黑色素类杆菌群菌株分离鉴定

本文对４４例牙源性脓肿（尖周脓肿２４例，牙周脓肿１２例，冠周脓肿８例）脓液标本中的产黑色素类杆菌群菌株进行分离、培养、鉴定。其中３８例存在产黑菌群，以中间型类杆菌阳性率最高。牙龈类杆菌在牙周脓肿中检出率最高。２４例尖周脓肿可分离出６株牙髓类杆菌而其它两种牙源性脓肿则无牙髓类杆菌，推测该菌与牙髓尖周感染的病理过程有关。     

顺丁烯二酸水溶液的热反应动力学

研究了不同温度、浓度条件下，顺丁烯二酸（顺酸）非催化反应网络，即顺酸可生成反丁烯二酸（反酸）和苹果酸，反酸与苹果酸存在可逆反应。建立了该反应网络的动力学模型。测定了不同反应条件下顺酸、反酸和苹果酸浓度随时间变化的规律，据此，动力学参数进行了估值。     

Identification of Leishmania donovani isolates from different kala-azar foci in China by kDNA hybridization.

kDNA sequence homology of Leishmania donovani isolates from three types of kala-azar foci in China were analyzed by using dot and Southern hybridization with biotin- and 32P-labelled probes. The results revealed kDNA sequence heterogeneity among Leishmania donovani isolates from the three kala-azar foci: sequence homology between isolates of hill and desert foci was higher than that between hill and plain foci isolates. The kDNA hybridization technique was also found to be specific and sensitive for direct identification of Leishmania in animal tissues. In a preliminary survey, kDNA hybridization of cutaneous tissue blots of 71 dogs from endemic regions showed a positive rate of 40.8%, and the rate of double positive cases (touch blot hybridization and bone marrow smear) reached 91.3%. The direct identification of Leishmania in tissues by kDNA hybridization seems to be a useful and convenient method for epidemiological study and clinical diagnosis, especially for species/strain characterization.     

单片机自动灌流系统设计及其医学应用

介绍一种用单片机构成的自动灌流控制系统。它以灌流压为控制指标，以ＬＤＢ－Ｍ电子蠕动泵作为执行机构，构成闭环控制系统，能实现用户设定的各种液流压曲线。系统内采用了ＥＥＰＲＯＭ存储器，可对用户设定的多达１０条灌流曲线进行长期保存。     

选择性髂内动脉结扎与栓塞对盆腔血供的影响

目的：旨在探讨选择性髂内动脉结扎与栓塞两种方法对盆腔血供的影响。方法：将两组犬在膀胱上动脉分支以下之髂内动脉分别行结扎与栓塞，对比观察两组膀胱创面出血、盆腔动脉造影及盆腔脏器组织学变化，以确定其盆腔脏器的血供情况。结果：①结扎组膀胱创面出血明显大于栓塞组；②结扎组髂内动脉侧支循环建立时间明显早于且数目多于栓塞组；③两组盆腔脏器均未见缺血坏死。结论：栓塞组阻断髂内动脉侧支循环的数目多于结扎组，故对盆腔血供的影响大于结扎组。避免髂内动脉阻断范围过广可减少盆腔脏器缺血坏死的机会。     

Is there disproportionate impairment in semantic or phonemic fluency in schizophrenia?

Phonemic and semantic fluency involve the capacity to generate words beginning with particular letters or belonging to particular categories, respectively. The former has been associated with frontal lobe function and the latter with temporoparietal function, but neuroimaging studies indicate overlap of underlying neural networks. Schizophrenia patients may experience disproportionate semantic fluency impairment owing to abnormal semantic organization; however, executive dysfunction in schizophrenia suggests possible disproportionate phonemic fluency impairment. Moreover, little is known about the diagnostic specificity of either verbal fluency deficit to schizophrenia or their stability over time. We examined 83 schizophrenia patients, 15 bipolar disorder patients, and 83 normal controls. Both fluency types were impaired in schizophrenia patients. Schizophrenia patients as a whole manifested disproportionate semantic fluency impairment relative to bipolar disorder patients, but only a subset of schizophrenia patients manifested disproportionate semantic fluency impairment relative to controls. Few characteristics, except to some extent paranoid-nonparanoid subtype, meaningfully differentiated schizophrenia patients with and without this disproportionate impairment. Verbal fluency measures were moderately stable over a 4-year period in schizophrenia patients and controls (.48 < rs < .79). These results mirror a literature that overall suggests a small degree of disproportionate semantic fluency impairment in schizophrenia, but also some heterogeneity in fluency deficits.     

人甲胎蛋白时间分辨免疫荧光分析试剂盒的研制

目的研制人甲胎蛋白(hAFP)时间分辨免疫荧光分析(TRFIA)试剂盒.方法采用双抗体夹心法建立AFP TRFIA 试剂盒,对试剂盒的各项指标进行评价.结果试剂盒的可测范围为l～1 000 U/ml,灵敏度为0.17 U/ml,精密度良好,批内和批间的精密度分别为3.3%～5.9%,3.7%～6.5%.与CEA、CA12-5、CA19-9、CA15-3、白蛋白无交叉反应.稳定性试验表明试剂可以在4℃稳定1年,37℃稳定7 d.426份正常血清标本测试该试剂盒的正常参考值范围是0～12 U/ml.用本试剂盒与国外同类试剂盒同时检测60份血清标本,其相关系数为0.995.结论试剂盒各项指标(灵敏度、精密度、特异性、稳定性、准确度)均达到临床检测要求,可替代国外同类产品试剂盒.     

Optical Pretargeting of Tumor with Fluorescent MORF Oligomers

Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate morpholinos (MORFs) for pretargeting using technetium-99m (^99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection. The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not previously been considered for pretargeting applications. Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25) is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner, the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance (SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25 was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or equal molar dosage of single-chain Cy5.5–MORF25 and were imaged. Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh. However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with only the kidneys. Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence inhibition optimized for pretargeting and other in vivo applications of optical imaging.