Novel HLA-A locus alleles including A*01012, A*0306, A*0308, A*2616, A*2617, A*3009, A*3206, A*3403, A*3602 and A*6604

This paper describes 10 novel HLA-A alleles that have been characterized by DNA sequencing. Seven alleles, A*0308, A*2616, A*3009, A*3206, A*3403, A*3602 and A*6604 carry motifs observed in other HLA-A alleles, suggesting that gene conversion has created this diversity. The remaining three alleles, A*01012, A*0306 and A*2617, contain polymorphisms not previously found in any "classical" class I allele. All alleles were identified due to unexpected probe hybridization patterns during routine SSOP typing. Exons 2 and 3 of each allele were subsequently characterized by DNA sequencing.     

Lipid A and Anti-Lipid A

Lipid A in free form, in crude antigen preparations, and on Formalin-treated Escherichia coli and Salmonella minnesota R595 was employed in studies of its antigenic composition, immunogenicity, and availability on gram-negative bacteria. Analyses with immunodiffusion and crossed immunoelectrophoresis of isolated lipid A preparations revealed three components. Inhibition experiments with enzyme-linked immunosorbent assay showed that the lipid A structure was not exposed on the tested smooth or rough E. coli strains or on S. minnesota R595. In crude O antigen preparations from some of the strains, however, lipid A was available for reaction with antibodies. The inaccessibility of lipid A on the bacterial surface may explain the poor protective capacity of anti-lipid A antibodies against bacterial infections. An enzyme-linked immunosorbent assay was more sensitive for measuring anti-lipid A antibody activity than indirect hemolysis or indirect hemagglutination. With an enzyme-linked immunosorbent assay it was shown that in rabbits the immunogenicity of lipid A was approximately the same when coated on erythrocytes or, as is more commonly done, when lipid A-coated hydrolyzed bacteria were used. Some antisera from rabbits immunized with E. coli of different serotypes showed activity against lipid A, with a higher frequency for antisera from rabbits immunized with R mutants.     

A meckelin-filamin A interaction mediates ciliogenesis

MKS3, encoding the transmembrane receptor meckelin, is mutated in Meckel-Gruber syndrome (MKS), an autosomal-recessive ciliopathy. Meckelin localizes to the primary cilium, basal body and elsewhere within the cell. Here, we found that the cytoplasmic domain of meckelin directly interacts with the actin-binding protein filamin A, potentially at the apical cell surface associated with the basal body. Mutations in FLNA, the gene for filamin A, cause periventricular heterotopias. We identified a single consanguineous patient with an MKS-like ciliopathy that presented with both MKS and cerebellar heterotopia, caused by an unusual in-frame deletion mutation in the meckelin C-terminus at the region of interaction with filamin A. We modelled this mutation and found it to abrogate the meckelin-filamin A interaction. Furthermore, we found that loss of filamin A by siRNA knockdown, in patient cells, and in tissues from Flna(Dilp2) null mouse embryos results in cellular phenotypes identical to those caused by meckelin loss, namely basal body positioning and ciliogenesis defects. In addition, morpholino knockdown of flna in zebrafish embryos significantly increases the frequency of dysmorphology and severity of ciliopathy developmental defects caused by mks3 knockdown. Our results suggest that meckelin forms a functional complex with filamin A that is disrupted in MKS and causes defects in neuronal migration and Wnt signalling. Furthermore, filamin A has a crucial role in the normal processes of ciliogenesis and basal body positioning. Concurrent with these processes, the meckelin-filamin A signalling axis may be a key regulator in maintaining correct, normal levels of Wnt signalling.     

Characteristics of transducing group A streptococcal bacteriophages A 5 and A 25

Summary The virulent, transducing, DNA-containing group A streptococcal bacteriophages A5 and A25 are 58 m in head size and have a flexible, noncontractile tail with a length of 180 m. The morphologic outline of the head is hexagonal. Treatment of the bacteriophages with potentially lethal ultraviolet radiation produced damages which were repairable by the Hcr⁺ streptococcal host strain K56, the host-cell reactivable sector being 0.9. These properties together with a demonstrable serological cross reaction show a close relationship between the two phage strains.     

Three newly identified A*24 alleles: A*2406, A*2413 and A*2414

Three previously unknown A24-related alleles were identified by PCR-SSO typing and confirmed by DNA sequencing in Australian Aboriginal populations (A*2406, 2413) and in individuals of South American descent (A*2414). A*2406 and A*2413 both have two adjacent (but different) nucleotide substitutions in codon 156 in exon 3 compared to A*2402, resulting in a single amino acid replacement in each allele. The South American A*2414 is apparently a hybrid between A2 and A24 with a segment of the A*24 sequence between codons 95 and 107 in exon 3 replaced with the A*02 sequence. Interallelic sequence exchange is the most likely mechanism in the generation of all three novel alleles. Compared to A*2402, the four amino acid substitutions in the A*2414 molecule would be expected to significantly change the shape of the peptide binding cleft, leading to selection of different peptide ligands. The single amino acid replacements in position 156 of the two Australian Aboriginal A*24 alleles may also have significant functional effects. In particular, Trp replacing Gin in position 156 (A*2406) is predicted to markedly reduce the volume of the peptide binding cleft, influence the interaction of HLA pockets with peptide side chains, and therefore, cause major changes in peptide presentation. These newly defined alleles may reflect the adaptive process of HLA genes to local environments.     

Distribution of adenosine A1, A2A and A2B receptors in human skeletal muscle

Many important physiological functions of skeletal muscle, such as glucose uptake, contraction and blood flow, have been proposed to be regulated via the action of adenosine on adenosine receptors. The cellular location of adenosine receptors in skeletal muscle is however, not known. The present study examined the distribution of A1, A2A and A2B adenosine receptors in human skeletal muscle using immunohistochemistry. All three receptor types were localized to vascular smooth muscle and endothelial cells, only the adenosine A2A and A2B receptors were observed in the plasma membrane and cytosol of the skeletal muscle. The finding was supported by results from western-blotting analysis. The cytosolic staining of the adenosine A2A receptor was slightly more intense in the type I muscle fibres, whereas the A2B receptor was almost absent in type I fibres. The present findings demonstrate for the first time, direct evidence for the existence of A2A and A2B adenosine receptors but absence of the A1 receptor in the sarcolemma and cytosol of skeletal muscle cells. The data also show existence of all three of the A1, A2A and A2B adenosine receptors in vascular cells of skeletal muscle tissue.     

DETECTION OF A1A2 AND A2AAm1 HETEROZYGOTES AMONG HUMAN A BLOOD GROUP PHENOTYPES

From the variations of α-N-acetylgalactosaminyltransferases activities with the pH, evidence was obtained for the recognition of A₁A₂ heterozygotes in normal A blood group sera. Besides, unusual transferase properties associated with two A₂ sera from individuals out of A^A_m1 siblings, lead to the identification of the very infrequent A₂A^A_m1 genotypes. These results strongly support the simultaneous coexistence of both A₁ and A₂ transferases in heterozygotes' sera, and bring some new information on the genetical background of the A_m phenotype. The meaning of transferase properties directly determined on whole sera is briefly discussed.     

某幼儿园一起手足口病暴发的现场流行病学调查报告

目的了解某幼儿园手足口病暴发的流行病学特征及造成传染的主要原因,为进一步做好该园手足口病防控工作提供依据。方法按照病例定义,电话开展病例搜索,结合现场流行病学调查情况,形成假设,采用1：2匹配的病例对照研究,对照选取同班同年龄组同性别的儿童,使用统一的调查表询问儿童的日常卫生习惯。结果该幼儿园从2010年3月16日至3月23日共发生9例临床诊断病例,3例实验室确诊病例,罹患病率为7.95%。以小班病例为主,3～4岁组比例高（8/12）。3份粪便检测出病原体CoxA16。有吸吮手指、吸吮玩具、饭前不洗手、便后不洗手、挖鼻孔、揉眼睛等任一不良卫生习惯是手足口病发病的危险因素（OR=12,95%CI=1.3～114）。结论幼儿不良卫生习惯是该幼儿园手足口病传播的主要原因。建议该园加强儿童不良卫生习惯的纠正,培养良好卫生习惯,以达到控制传染的目的。     

THERAPEUTIC COMMUNITIES: A PROBLEM OR A SOLUTION FOR PSYCHIATRY? A SOCIOLOGICAL VIEW

This paper reviews the place of the therapeutic community in the mental health field, using a sociological framework to understand some key factors that have shaped the field and its response to this approach to therapy. The therapeutic community treatment method in mental health has been contested over the years. It has challenged conventional professional frameworks, it has dealt with a difficult client group, and it has been hostile to or at least awkward about establishing its evidence base. In this paper I reflect on the ‘politics of evidence’ in contested fields. I draw on the analysis of ‘fields’ from the work of French sociologist Pierre Bourdieu, and the analysis of scientific knowledge from an area of the social study of science, ‘actor-network theory’. I argue that evidence is not neutral in contested fields, and that the technology of trials is not balanced with a theoretically informed understanding of the phenomena under scrutiny (causality versus meaning).