Implementation of HaemScreen, a workplace-based genetic screening program for hemochromatosis

There is debate as to whether community genetic screening for the mutation(s) causing hereditary hemochromatosis (HH) should be implemented, due to issues including disease penetrance, health economic outcomes, and concerns about community acceptance. Hemochromatosis is a common preventable iron overload disease, due in over 90% of cases to C282Y homozygosity in the HFE gene. We are, therefore, piloting C282Y screening to assess understanding of genetic information and screening acceptability in the workplace setting. In this program, HaemScreen, education was by oral or video presentation in a group setting. C282Y status was assessed by polymerase chain reaction (PCR) and melt-curve analysis on DNA obtained by cheek-brush sampling. Of eligible participants, 5.8% (1.5-15.8%) attended information and screening sessions, of whom 97.7% (5571 individuals) chose to be tested. Twenty-two C282Y (1 : 253) homozygotes were identified and offered clinical follow-up. There were 638 heterozygotes (1 : 8.7). The determinants for participation have been analyzed in terms of the principles outlined in the Health Belief Model. Widespread screening for HH is readily accepted in a workplace setting, and a one-to-many education program is effective. The level of participation varies greatly and the advertizing and session logistics should be adapted to the specific features of each workplace.     

一个遗传性智力迟缓家系的分析

目的 寻找由DNA损伤引起的人类表型缺陷，为人类遗传资源的收集与保藏以及人类基因结构与功能的研究打下基础。方法 通过实地调查得到表型缺陷家系，然后进行系谱分析。结果 得到一个遗传性智力迟缓家系，3代11位成员中有2例患者。结论 遗传性智力迟缓是由DNA损伤引起的人类表型缺陷；该病症符合X-连锁隐性遗传。     

基于遗传算法的经颅磁刺激线圈阵列设计与场分布计算

为解决经颅磁刺激的兴奋点定位问题提出了以圆环面聚焦线圈阵列实现电磁聚焦的方案。而后,使用经过改进的自适应遗传算法对注入阵列各单元线圈电流的大小和相位进行了优化,在目标区域内很好的实现了电磁聚焦。通过计算,显示了线圈阵列在优化后的电流组态下产生的磁场和电场在计算区域内的分布和二维等高线图,表明了该聚焦线圈阵列可在目标区域产生具有良好聚焦性能的电场和磁场分布,并具有可同时聚焦至多个目标的能力。     

X-linked severe combined immunodeficiency syndrome: the first Korean case with gamma c chain gene mutation and subsequent genetic counseling

X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the gamma c chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for gamma c chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain gene is useful for definite diagnosis and genetic counseling for X-SCID.     

Genetic modification of the spontaneous rho − mutability in Saccharomyces cerevisiaee

Summary The phenotypic trait starry colony in Saccharomyces is associated with a high spontaneous rho ^– petite mutability. Genetic analysis of this trait has shown the high rho ^– mutability to be caused by several modifying genes present together in the strains studied. Every single modifying gene produces only a relatively small enhancement of the rho ^– mutability.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.     

Heart period variability of trained and untrained men at rest and during mental challenge

The effect of aerobic training on parasympathetic reactivity to mental stress is unclear. Thus, the parasympathetic response, as assessed by time series analysis of heart period variability (HPV_ts), of 10 trained male runners (trained group), 10 inherently low resting heart rate untrained men (low HR group), and 10 normal resting HR men (control group) at rest and to two mental stressors was examined. Participants completed a mental arithmetic and Stroop task. Resting HPV_ts at high and medium frequencies was significantly greater for the trained and the low HR groups than for the control group. Significantly greater decreases in HPV_ts at the medium frequency during arithmetic recovery were measured for the trained and low HR groups compared with the response of the control group. Significantly greater decreases in HPV_ts at both the the high and medium frequencies during the first two epochs of the Stroop occurred only for the trained and low HR groups. These results suggest that the greater HPV_ts at rest and decline in HPV_ts during and after mental challenge is influenced by both aerobic training and genetic inheritance.     

Standardization for image characteristics in telemammography using genetic and nonlinear algorithms

As the soft copy reading and computer assisted diagnosis (CAD) in mammography become more and more important, the standardization of digital images becomes paramount. Telemammography and telemedicine requires the standardization for image characteristics, such as image resolution, bit-depth and intensity response. Soft copy reading and CAD in mammography are both dependent on the characteristics of the source of the digital data, either direct digital mammography or digitized screen-film mammography. An algorithm developed on images from one database may not perform well as on images from another database (with a different digitization). In this paper, we describe two methods based on a genetic algorithm and a nonlinear algorithm for standardization of digitized and digital mammography. The proposed standardization techniques are based on geometric and intensity transformations that are discovered using a set of calibration images. A set of transformation algorithm is used to search for the best standardization.     

产前筛查和基因多态性位点在唐氏综合征产前诊断中的应用

目的 在建立可靠的产前筛查方法的同时，采用快速，简便，准确的产前诊断方法，防止唐氏综合征（DS）患儿的出生，方法 采用酶联免疫方法测定妊娠14-20w孕妇血清甲胎蛋白（AFP）和绒毛膜促性腺激素β亚基（β-HCG）浓度，结合孕妇年龄，孕周和体重，用计算机软件进行分析，得到每位孕妇所怀胎儿DS风险系数，对筛查出胎儿唐氏综合征高风险孕妇，再利用21号染色体上的6个多态性位点对其作产前基因诊断。结果 经产前筛查，在395例孕妇中发现10例胎儿唐氏综合征高风险孕妇，其中1例产前基因诊断为胎儿唐氏综合征，与染色体核型分析结果相符。结论 产前筛查结合基因多态性在唐氏综合征产前诊断中具有很好的应用价值。     

Antigens targeted to the Leishmania phagolysosome are processed for CD4+ T cell recognition

Processing of antigen for recognition by class II-restricted CD4⁺ T cells occurs within acidic compartments of the antigen-presenting cell. The exact nature of this compartment has yet to be precisely defined, however, but may vary depending upon the cell type studied and the antigen used. The acidic compartments of macrophages are also responsible for the degradation of ingested micro-organisms and play host to others which are adapted to an intracellular existance. To determine whether the phagolysosome (PL) formed in activated macrophages after ingestion of Leishmania parasites is also a site for entry of antigen into the class II presentation pathway, we have used the approach of genetic transformation. Hence, Leishmania were transfected with the genes for the protein antigens ovalbumin (OVA) and β-galactosidase (β-gal) and after infection were able to deliver these antigens specifically into the PL. Delivery of antigen to this site resulted in the ability of infected macrophages to present these antigens to antigen-specific CD4⁺ T cells. After taking into account the absolute levels of antigen uptake by macrophages, a 4-h processing period for OVA delivered by this or a soluble route led to equivalent levels of T cell activation. Unlike macrophages pulsed with soluble OVA, those with PL-targeted OVA still retained the ability to stimulate T cells after a 24-h processing period. This enhanced lifespan of antigen in macrophages corresponded to the kinetics of degradation of the parasite, suggesting slow release of antigen into the processing pathway. β-gal presentation from the PL was tenfold less efficient under the same conditions. In addition to providing the first information on antigen processing in a protozoan PL, these studies highlight the usefulness of genetically transformed parasites for these types of studies.