Genetics of the low density lipoprotein receptor:

Fibroblast association (plasma membrane binding plus intracellular accumulation) and degradation of radioiodinated low density lipoprotein (125I-LDL) index plasma membrane LDL receptor activity. Cultured fibroblasts from 23 subjects affected with familial hypercholesterolemia (HC) and from 95 subjects without HC (non-HCs) were tested for 125I-LDL association and degradation. Both LDL receptor activity indices were twice as high in non-HC and HC heterozygous cell strains. This is compatible with a major gene effect on LDL receptor activity. However, a considerable overlap between non-HC and HC heterozygous values was found in the 125I-LDL association assay [median (range) 970 (330-2500), and 450 (250-490), respectively] and in the degradation assay [median (range) 810 (280-2020), and 470 (160-790), respectively]. The values are expressed as ng 125I-LDL X mg cell protein-1 X 4.5 h-1. These great overlaps in the LDL receptor activity indices support the view that the influence of LDL receptor activity on the HC phenotype may be smaller than believed previously. Furthermore, for the diagnosis of HC, these LDL receptor activity assays are far more expensive and have less sensitivity and specificity than simple serum cholesterol determination. The LDL receptor-dependent 125I-LDL association values for the HC heterozygous individuals clustered into four groups. Family data supported the hypothesis that this variation could be due to four different LDL receptor variants, each coded for by different alleles at the LDL receptor locus. If confirmed, this finding may have implications for the understanding of the variable expression of HC and also of the genetic impact on lipoprotein metabolism and susceptibility to atherosclerosis in non-HCs.     

Radial artery running beneath the biceps tendon and its interrelation between the radial recurrent arteries

A radial artery running beneath the biceps tendon was found in the cadaver of a Japanese woman during a student dissection course at Kumamoto University School of Medicine in 2006. The brachial artery bifurcated into the radial artery and the ulnar artery in the cubital fossa, and the radial artery twisted laterally running beneath the biceps tendon, and when it was situated laterally to the tendon, twisted distally at the level of the radial tuberosity, and then twisted medially again. After the radial artery passed over the biceps tendon, it turned distally and continued as a normal radial artery. The superficial brachial artery, which coexisted with the brachial artery, was given off from the axillary artery and it continued to the final twist of the radial artery. The course of this radial artery is similar to the arterial rings surrounding the biceps tendon, found during the same dissection course. The arterial rings were formed between the brachial artery and the radial artery, and their proximal origins ran beneath the biceps tendon, while the distal origins were superficial. The present arterial variation is thought to have occurred when the normal part of the radial artery in the cubital fossa was substituted by the arterial ring, coexisting with the superficial brachial artery, which usually disappears during normal development. Furthermore, it is suggested that a part of the arterial ring always remains as a radial recurrent artery.     

The cholesteryl ester transfer protein (CETP) locus as a candidate gene in abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a relatively common disease of the elderly presenting as progressive dilatation of the abdominal aorta. The condition shows a pronounced tendency to cluster in families, indicating a genetic component in the disease aetiology. We have screened the cholesteryl ester transfer protein (CETP) gene, which has been proposed as a candidate gene in AAA, by means of SSCP, DNA sequencing and restriction analysis in a cohort of patients with AAA and a matching control group drawn from the Irish population. The analysis has demonstrated sequence variation at four sites in the CETP gene: an A-T transversion in exon 9 (producing a Lys309-Stop codon substitution), a G-A transition in exon 14 (producing a conservative Va1421-Ile substitution), a C-T transition in intron 12 and a G-A transition in intron 15. None of the last three sites corresponded with sites of functional significance in the protein, suggesting that this reflects neutral polymorphism at the CETP locus. Furthermore, the frequencies of these four polymorphisms in the AAA patient and control groups were not significantly different. These data therefore suggest that CETP may be excluded as a candidate gene in abdominal aortic aneurysm.     

Genetic variation in the male courtship sound ofDrosophila littoralis

Drosophila littoralis males and females emit sounds during courtship by vibrating their wings. Genetic variation in the male courtship sound of this species was studied by analyzing the sounds of males of 42 fresh isofemale strains from three localities in Finland and those of several laboratory strains originating from Europe and Caucasus. Among the fresh strains, the mean number of sound cycles in a pulse varied from 12 to 17 cycles, the length of a pulse from 39 to 51 ms, the length of a sound cycle from 2.9 to 3.6 ms, and the length of an interpulse interval (ipi) from 280 to 400 ms. The sounds of the old laboratory strains differed from each other more than the sounds of the fresh strains. There was, however, no sign of geographic differentiation.This study was aided by funds from The Academy of Finland.     

Genome and antigenic analysis of influenza A (H3N2) viruses isolated from an epidemic in a closed community of Carmelite nuns

Eighteen influenza A (H3N2) viruses were isolated during a single outbreak in a closed community of Carmelite nuns. Serological analysis of the virus haemagglutinin (HAs), using a panel of monoclonal antibodies, demonstrated antigenic microheterogeneity. In contrast, no significant biochemical differences were detected in viral genes by RNA:RNA hybridisation or in structural or nonstructural polypeptides analysed by high-resolution polyacrylamide gel electrophoresis (PAGE) or by limited proteolysis followed by PAGE. Influenza A (H3N2) viruses isolated in the vicinity of the convent were distinguishable from each other and from the epidemic viruses isolated in the convent both antigenically and biochemically.     

Cholera toxin adjuvant greatly promotes antigen priming of T cells

Cholera toxin (CT) given perorally is a powerful mucosal immunogen and adjuvant. Information that explains the adjuvant effect of CT may be used for the development of more effective oral vaccines and might also contribute to our understanding of the mechanisms involved in regulating mucosal immunity. The present study was undertaken to investigate if CT administered together with keyhole limpet hemocyanin (KLH) would act to promote or inhibit priming of KLH-specific T cells and whether the adjuvant effect of CT is restricted to mucosal immune responses or is a generalized phenomenon due to direct immunomodulating effects of CT. We found that CT adjuvant greatly augmented the effectiveness of a single oral priming immunization with KLH: re-challenge with KLH in vitro 1 week following immunization gave several-fold stronger proliferation in KLH-specific spleen, mesenteric lymph node, Peyer's patch and gut lamina propria T cells from KLH + CT adjuvant as opposed to KLH only-treated mice. Moreover, several-fold stronger cytokine production, i.e. interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10 and interferon-Y accompanied the enhanced proliferative response of T cells from CT adjuvant-treated mice. The adjuvant effect of CT was not restricted to mucosal immune responses but was evident also following a single parenteral immunization with KLH + CT. Limiting dilution analysis revealed that CT adjuvant promoted a 20- to 40-fold increase in the frequency of primed KLH-specific T cells. Phenotypic and functional analyses clearly demonstrated that CT adjuvant primarily enhanced priming of CD4⁺ rather than CD8⁺ T cells and the pattern of lymphokine secretion disclosed that CT most probably promoted antigen priming of both T_hl and T_h2 type of CD4⁺ T precursor cells.     

Ethnic variation in the HER-2 codon 655 genetic polymorphism previously associated with breast cancer

HER-2, a protooncogene located on chromosome 17q21, encodes a transmembrane glycoprotein (p185) with tyrosine kinase activity. Alterations of the HER-2 gene have been implicated in the carcinogenesis and prognosis of breast cancer and other solid tumors. It is also a cancer-therapeutic target for antibody-based therapy against the HER-2 protein. A single-nucleotide polymorphism (SNP) at codon 655, resulting in a G-to-A transition (Ile655Val) in the transmembrane domain-coding region of this gene has been associated with an increased risk of breast cancer, particularly among younger women. To understand the importance of this finding throughout the world, we evaluated this polymorphism in Ghanaian, Kenyan, Sudanese, Caucasian, African–American, Saudi, and Filipino subjects using a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the Val allele, which is associated with increased breast cancer risk, was highly variable between populations (0%–24%). Continental African populations had a lower frequency of the Val allele than did Saudi, Chinese, Filipino, Caucasian, and African–American subjects. The data suggest that this SNP has variable frequency in different ethnic groups. The findings in this study correspond with the lower incidence and lower risk of breast cancer in African women compared with Caucasian and African–American women. Received: December 13, 2001 / Accepted: January 16, 2002     

脑动脉DSA形态分析及其意义

目的：探讨脑血管造影各主要动脉的投影规律及其分支的显示率，为脑血管疾病的影像诊断和介入治疗提供重要参考。方法：随机抽取140例全脑血管DSA系列图像，选择其中无脑血管疾病的51例进行观察。分别统计颈内动脉和椎动脉造影时正常脑血管各主要分支的显示率；归纳大脑前动脉A1段、大脑中动脉M1段及大脑后动脉P1段在平面上的投影规律并分析总结了脑动脉的正常解剖学特征及其变异。结果：①脑底动脉变异较大；②颈内动脉照影时OA、AChA、ACoA、PCoA、ACA和MCA的显示率分别为96.1％、92．2％、52．9％、69．6％、100％和100％；③椎动脉造影时PICA、AICA、BA、SCA、PCA和PCoA的显示率分别为66．7％、62．7％、100％、70．6％、80．4％和41．2％。结论：①尽管脑底血管实际解剖关系较为复杂，但造影时反映到平面上可简捷的用“水平、上升、下降”等来描述血管的形态和走行；②虽然是平面图像，通过调整投照体位仍可非常逼真的反映血流的动态变化。     

The Foot and Mouth Disease Virus Type O Outbreak of 1992 Is Not Related to Vaccine Strain (O/R2/75)

Vaccination is the only pragmatic approach to control foot and mouth disease in India. Strict quality control measures are essential to supply potent vaccine to the field application, in addition to monitoring the performance of the vaccine in the field. During the process of monitoring, an outbreak of FMD in vaccinated animals caused by type “O” virus in Tanjavur district of Tamil Nadu and a type “O” virus from unvaccinated herd of Karnataka were studied. Field isolates and vaccine virus were sequenced and analyzed. Data indicated that the virus from the outbreak in vaccinated cattle was a variant which could escape neutralization by antibodies against vaccine virus. This revised version was published online in August 2006 with corrections to the Cover Date.     

抗同系小鼠白血病细胞单克隆抗体的研究

用可移植性小鼠淋巴细胞性白血病腹水瘤细胞克隆株(LAC-1)细胞免疫同系小鼠,常规方法融合、筛选获得四株分泌特异抗体杂交瘤株。所得McAb能特异地与LAC—1细胞结合,但不能与正常或经ConA转化的小鼠胸腺细胞以及其它多种小鼠瘤细胞起结合反应。ELISA检测显示,McAb与LAC—1细胞培养上清液中提取的病毒作用时未发现阳性反应。细胞介导的细胞毒实验表明,将McAb预先与LAC—1细胞孵育后能显著抑制T杀伤细胞对靶细胞的特异性杀伤作用,免疫印迹试验分析发现McAb识别的LAC—1细胞靶抗原分子量为41KD。