Tolerance in TCR/Cognate Antigen Double-Transgenic Mice Mediated by Incomplete Thymic Deletion and Peripheral Receptor Downregulation

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed with transgenic mice expressing the cognate antigenic protein under the control of the H- 2K^b promoter. Double-transgenic mice show negative selection of thymocytes at the CD4⁺8⁺TCR¹⁰ to CD4⁺8⁺TCR^hi transition stage. A few CD8 T cells, however, escape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulated levels of the CD44 memory marker. Such cells do not proliferate upon exposure to antigen stimulation in vivo or ex vivo, however, they can develop low but detectable levels of antigen-specific cytotoxic function after stimulation in vitro in the presence of IL-2.     

Glucose preferences in wild and domestic guinea pigs

Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body $\text{wt.}{}^{\mathrm{<mtext>3</mtext><mtext>4</mtext>}}$ during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.     

Seven novel and four recurrent point mutations in the factor VIII (F8C) gene

Haemophilia A is a X‐linked bleeding disorder, caused by deficiency in the activity of coagulation factor VIII due to mutations in the corresponding gene. The most common defect in patients is an inversion of the factor VIII gene that accounts for nearly 45% of individuals with severe hemophilia A. Point mutations and small deletions/insertions are responsible for the majority of cases with moderate to mild clinical course and for half of the severe hemophilia A occurrences. The majority of these mutations are “private”, because of the high mutation rate for this particular gene. We report on eleven pathological changes in the factor VIII sequence detected in male patients with haemophilia A or in female obligate carriers. Seven of these mutations are novel [E204N, E265X, M320T, F436C, S535C, N2129M and R2307P] and four have been previously identified [V162M, R527W, R1966X, and R2159C]. Genotype‐phenotype correlations and computer prediction analysis on the effect of missense mutations on the secondary structure of the factor VIII protein are performed and the relationships evaluated. © 2001 Wiley‐Liss, Inc.     

动态观察PSA和F PSA/PSA对诊断前列腺癌的临床价值

为了评价游离前列腺抗原（F PSA）／前列腺抗原（PSA）比值和PSA动态变化（年变化率）在前列腺癌诊断中的应用价值。本文应用ELISA追踪检测PSA在4～10μg／L范围患者在不同时段内PSA水平，并与正常人进行对照，利用ROC曲线，评价FPSA／PSA比值和PSA年变化率两项指标在前列腺癌诊断时的预示价值。结果表明：前列腺癌患者的FPSA／PSA比值和PSA年变化率与非前列腺癌组之间具有显著性差异（P〈0．001），当FPSA／PSA比值的临床判断值为0．21时，诊断灵敏度为93．5％，特异性为91.4％；当PSA年变化率的临床判断值为0．85％。诊断灵敏度为82．6％，诊断特异性为97．9％。前列腺增生患者FPSA／PSA比值与正常人之间无显著性差异（P〉0．05），而PSA年变化率与正常人比较具有显著性差异（P＜0．001）。提示FPSA／PSA比值和PSA年变化率有助于PSA在4～10μg／L范围的患者前列腺癌的诊断。     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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中国广东人CYP2F1基因遗传多态性研究

目的检测广东地区正常人群和鼻咽癌患者中细胞色素P450酶系CYP2F1基因的多态性，并分析该基因遗传多态性与鼻咽癌易感性的关联。方法采用直接测序法检测40例鼻咽癌患者全血标本中CYP2F1基因全部10个外显子的多态性变化。对于等位基因频率较高的多态性位点，进一步采用错配聚合酶链反应．限制性片段长度多态性检测368例鼻咽癌患者和344名正常对照人群中该位点的等位基因频率。结果在40例鼻咽癌样本中，共检测到CYP2F1基因的35个单核苷酸多态性。其中，10个单核甘酸引起编码的氨基酸改变，1个移码突变，15～16bp之间插入C引起移码突变（15-16ins C），该等位基因频率为25％。但病例-对照分析却未能显示该位点突变与鼻咽癌易感的相关性（P〉0．05）。结论中国广东人的CYP2F1基因遗传多态性位点较多，但暂未发现与鼻咽癌的易感性关联的单一多态位点，多个多态性位点或不同基因多态性位点的协同互补作用可能才是鼻咽癌发生发展的关键影响因素。     

Immunohistochemical analysis of centromere protein F expression in buccal and gingival squamous cell carcinoma

Centromere protein F (CENP-F) expression (localization and characteristics) in relation to tumor clinicopathological parameters was immunohistochemically examined and evaluated in 47 archival biopsy specimens of buccal and gingival squamous cell carcinomas (SCC). Centromere protein F expression was detected in 79% of the samples. An increase in the labeling index (LI) with WHO grading was obtained ( P  < 0.05). Correlations were obtained between the CENP-F LI and tumor size ( P  < 0.05). Immunoelectron microscopy showed CENP-F nuclear staining as punctate or fine dots. The present study shows that CENP-F expression and detection of a more specific cell subpopulation presents a theoretical advantage for the analysis of the precise cell cycle of G₂ to M cells, compared to Ki-67.     

Nonrandom chromosomal changes in untreated retinoblastomas

The karotypic patterns of 15 retinoblastomas were examined. Five tumors were found to have two distinct stem lines and, therefore, the chromosomal patterns of 20 tumor cell lines are reported. Three nonrandom chromosomal changes, namely, a loss of a chromosome #13, the presence of an i(6p), or a trisomy of 1q were observed. The potential importance of these chromosomal changes in tumor development is discussed, particularly the loss of a chromosome #13 or the gain of an i(6p). At least one of the three chromosomal changes was found in 75% of the tumor lines analyzed.     

棘球蚴内容物导致肺损害的研究

目的 :观察棘球蚴囊内容物攻击兔所至肺功能和形态的损害。建立囊型包虫肺栓塞的动物模型。方法 :取囊型包虫内容物 ,分离出囊砂 ,与囊液配成 5 %的悬浊液。 2 1只家兔 ,分 3组 :Ⅰ :生理盐水组 ,Ⅱ :澄清囊液组 ,Ⅲ :囊砂悬浊液组。每只家兔都置入股动脉导管及股静脉导管。依照上述分组按 2mL/kg体重分别自静脉导管注射生理盐水、澄清囊液或含囊砂的悬浊液。于注射后 ( 5、30、6 0min)动态监测MAP、血气指标及血清血管活性物质(ET - 1、TXB2 、6 -keto -PGF1α)水平的变化。指标测定后 ,行肺部ECT检查。最后取出动物肺脏行光镜病检。结果 :Ⅲ组和Ⅱ组在注射后均出现MAP、血气指标的明显降低 (P <0 .0 5 )和血清TXB2 、6 -keto -PGF1α的升高 (P <0 .0 5 ) ,尤以Ⅲ组最明显 (P <0 .0 5 )。各组动物血清ET - 1水平在注射前后无明显变化 (P >0 .0 1)。ECT显示Ⅲ组动物肺部放射性缺损 ,Ⅱ组动物肺部放射性减弱。Ⅲ组肺脏病检见头节广泛栓塞于肺小动脉、微小动脉中 ,肺脏呈“急性呼吸窘迫综合症样”改变。Ⅱ组肺组织出现淤血、水肿及炎细胞浸润。结论 :Ⅲ组动物基本能够模拟出囊型包虫病肺栓塞的临床表现。囊液中有形成分在肺损害中起着重要的作用。TXB2 、6 -keto -PGF1α参与了肺损伤病理过程。     

Phenotypic expansion of Bosch–Boonstra–Schaaf optic atrophy syndrome and further evidence for genotype–phenotype correlations

Bosch–Boonstra–Schaaf Optic Atrophy Syndrome (BBSOAS) is an autosomal dominant neurodevelopmental disorder caused by loss‐of‐function variants in NR2F1 and characterized by visual impairment, developmental delay, and intellectual disability. Here we report 18 new cases, provide additional clinical information for 9 previously reported individuals, and review an additional 27 published cases to present a total of 54 patients. Among these are 22 individuals with point mutations or in‐frame deletions in the DNA‐binding domain (DBD), and 32 individuals with other types of variants including whole‐gene deletions, nonsense and frameshift variants, and point mutations outside the DBD. We corroborate previously described clinical characteristics including developmental delay, intellectual disability, autism spectrum disorder diagnoses/features thereof, cognitive/behavioral anomalies, hypotonia, feeding difficulties, abnormal brain MRI findings, and seizures. We also confirm a vision phenotype that includes optic nerve hypoplasia, optic atrophy, and cortical visual impairment. Additionally, we expand the vision phenotype to include alacrima and manifest latent nystagmus (fusional maldevelopment), and we broaden the behavioral phenotypic spectrum to include a love of music, an unusually good long‐term memory, sleep difficulties, a high pain tolerance, and touch sensitivity. Furthermore, we provide additional evidence for genotype–phenotype correlations, specifically supporting a more severe phenotype associated with DBD variants.