HLA-B specificities and w4, w6 specificities are on the same polypeptide.

The human alloantigenic specificities w4 and w6, which are products of a diallelic system genetically associated with the HLA-B locus, have been solubilized by papain digestion of membranes from the lymphoblastoid cell line, RPMI 4265. The w4 and w6 specificities copurified with the HLA-B locus products, HLA-B7 and HLA-B12. Sequential immunoprecipitation experiments were performed using alloantisera to HLA-B7, HLA-B12, w4 and w6, and a purified HLA-B7, B12, w4, w6 antigen pool labeled with 125I-Bolton-Hunter reagent. These experiments demonstrated directly that HLA-B7 and w6, which are genetically associated with each other, are different antigenic determinants on the same molecule, while HLA-B12 and w4, also genetically associated, are distinct antigenic determinants on a second molecule. Arguments are presented which suggest that the HLA-B determinants and w4, w6 determinants are in fact on the same polypeptide, and the genetic implications of the findings are discussed.     

Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea viruses type 2

Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Besides the segregation into two distinct species (BVDV1/BVDV2) two different biotypes, a cytopathic (cp) and a noncytopathic (ncp) biotype, are distinguished based on their behavior in epithelial cell cultures. One of the most serious forms of BVDV infection affecting immunocompetent animals of all ages is severe acute BVD (sa BVD) which is caused by highly virulent ncp BVDV2 strains. Previous studies revealed that these highly virulent ncp viruses cause cell death in a lymphoid cell line (BL3) which is not clearly associated with typical apoptotic changes (e.g. PARP cleavage) observed after infection with cp BVDV. To further characterize the underlying molecular mechanisms, we first analyzed the role of the mitochondria and caspases as key mediators of apoptosis. Compared to infection with cp BVDV2, infection with highly virulent ncp BVDV2 resulted in a delayed and less pronounced disruption of the mitochondrial transmembrane potential (DeltaPsi(m)) and a weaker activation of the caspase cascade. In contrast, infection with low virulence ncp BVDV2 showed no significant differences from the uninfected control cells. Since different pro- and anti-apoptotic cellular signaling pathways may become activated upon virus infection, we compared the effect of different BVDV2 strains on cellular signaling pathways in BL3 cells. Stress-mediated p38 MAPK phosphorylation was detected only in cells infected with cp BVDV2. Interestingly, infection with highly virulent ncp BVDV2 was found to influence the phosphoinositide 3-kinase (PI3K)-Akt pathway. This indicates that BL3 cells respond differently to infection with BVDV depending on virulence and biotype.     

IL-6 trans-signaling: the heat is on

The molecular consequence of the fever response has been illuminated by a recent study showing that a temperature shift to 40 degrees C resulted in increased leukocyte adhesion to tissue sections, which was mediated by L-selectin activation in lymphocytes. This L-selectin activation during heat responses was dependent on IL-6 trans-signaling via the soluble IL-6R.     

The jury is in: p73 is a tumor suppressor after all

While p53 has been extensively characterized as a tumor suppressor, it has been more difficult to determine whether p63 and/or p73 play a similar role. Every system in which these family members have been studied, from cells to animal models to human tissues, seems to create more questions than answers. Tomasini and colleagues (2677-2691) demonstrate that one isoform of p73 is responsible for preventing tumor formation in vivo, providing critical validation of an isoform-based model of p73 function.     

A boundary-representation method for designing whole-body radiation dosimetry models: pregnant females at the ends of three gestational periods--RPI-P3, -P6 and -P9

Fetuses are extremely radiosensitive and the protection of pregnant females against ionizing radiation is of particular interest in many health and medical physics applications. Existing models of pregnant females relied on simplified anatomical shapes or partial-body images of low resolutions. This paper reviews two general types of solid geometry modeling: constructive solid geometry (CSG) and boundary representation (BREP). It presents in detail a project to adopt the BREP modeling approach to systematically design whole-body radiation dosimetry models: a pregnant female and her fetus at the ends of three gestational periods of 3, 6 and 9 months. Based on previously published CT images of a 7-month pregnant female, the VIP-Man model and mesh organ models, this new set of pregnant female models was constructed using 3D surface modeling technologies instead of voxels. The organ masses were adjusted to agree with the reference data provided by the International Commission on Radiological Protection (ICRP) and previously published papers within 0.5%. The models were then voxelized for the purpose of performing dose calculations in identically implemented EGS4 and MCNPX Monte Carlo codes. The agreements of the fetal doses obtained from these two codes for this set of models were found to be within 2% for the majority of the external photon irradiation geometries of AP, PA, LAT, ROT and ISO at various energies. It is concluded that the so-called RPI-P3, RPI-P6 and RPI-P9 models have been reliably defined for Monte Carlo calculations. The paper also discusses the needs for future research and the possibility for the BREP method to become a major tool in the anatomical modeling for radiation dosimetry.     

2010年扬州市一类疫苗预防接种不良反应的监测

目的监测扬州市一类疫苗预防接种反应发生情况。方法采用描述流行病学方法对扬州市预防接种反应监测资料进行分析研究。结果 2010年扬州市11种一类疫苗共接种741552剂次,报告预防接种反应363例,反应发生率为4.90/万;江都市最高为6.77/万、开发区最低为3.31/万,不同地区预防接种反应差异有统计学意义（χ2=25.17,P〈0.01）;7月最高为14.23/万,2月最低为1.32/万,不同时间预防接种反应差异有统计学意义（χ2=163.99,P〈0.01）;反应发生率以无细胞百白破三联（DPaT）最高为13.49/万,脊灰疫苗（PV）最低为0.46/万,不同疫苗预防接种反应差异有统计学意义（χ2=365.44,P〈0.01）;发生反应类型一般反应以发热为主,异常反应以过敏性皮疹为主;疑似预防接种反应监测及时报告率、调查率、诊断分类率和规范处置率均为100%。平均每报告处置1人的费用为0.07万元。结论扬州市预防接种反应发生率低,预防接种反应监测系统比较完善,建议加强预防接种反应监测、规范安全接种操作,增强工作责任心,提高反应处置能力,增加处置经费的投入。     

The idiotypic specificities of lymphocytes in human monoclonal gammopathies: analysis with the fluorescence activated cell sorter

Four monoclonal IgG kappa gammopathies were studied with anti-idiotypic sera and the percentage of lymphocytes bearing such idiotypes was evaluated with a fluorescence activated cell sorter (FACS). A large percentage (10-15%) of peripheral lymphocytes bearing receptors with the same idiotypic specificities as the M component was observed in multiple myeloma (MM) and in monoclonal gammopathy of undetermined significance (MGUS), suggesting a malignant origin for both these diseases. Capping-endocytosis and resynthesis experiments showed that these idiotypic receptors were not simply adsorbed on the cell membrane, but actually synthesized by the cells bearing them. Experiments performed after effective conventional chemotherapy showed a strong reduction of the idiotypic compartment in only one MM patient.     

Structural analysis of monoclonal anti-arsonate antibodies: idiotypic specificities are determined by the heavy chain

Hybrid immunoglobulin molecules were constructed from the isolated heavy and light chains of monoclonal anti-arsonate antibodies which differed in their expression of a cross-reactive idiotype. The reconstructed molecules were tested for public and private idiotypic determinants associated with the A-strain response to the hapten p-azophenylarsonate and it was found that both an appropriate heavy chain and an appropriate light chain were required for expression of idiotypic determinants. While appropriate heavy chains could be derived only from idiotype-positive antibodies, appropriate light chains could be derived not only from idiotype positive antibodies, but also from certain idiotype-negative molecules. Similarly, recombinant (hybrid) molecules constructed from two idiotype-positive immunoglobulins differing quantitatively in the degree of idiotypic character, expressed the character at a level which correlated with that of the heavy chain donor. Thus, while the serological expression of idiotypic determinants occurs only in the context of the appropriate VHVL combination, these data demonstrate that the determinants comprising the major cross-reactive idiotype of the anti-arsonate response of A/J mice have their bases in heavy chain structures.     

Tissue-specific differences in 2-fluoro-2-deoxyglucose metabolism beyond FDG-6-P: a 19F NMR spectroscopy study in the rat

2-Fluoro-[(18)F]-2-deoxy-glucose (FDG) is a positron-emitting analogue of glucose used clinically in positron emission tomography (PET) to assess glucose utilization in diseased and healthy tissue. Originally developed to measure local cerebral glucose utilization rates, it has now found applications in tumour diagnosis and in the study of myocardial glucose uptake. Once taken up into the cell, FDG is phosphorylated to FDG-6-phosphate (FDG-6-P) by hexokinase and was originally believed to be trapped as a terminal metabolite. This 'metabolic trapping' of FDG-6-P forms the basis of the analysis of PET data. In this study, we have used (19)F NMR spectroscopy to investigate FDG metabolism following the injection of a bolus of the glucose tracer into the rat (n=6). Ninety minutes after the (19)FDG injection, the brain, heart, liver and kidneys were removed and the (19)FDG metabolites in each were extracted and quantified. We report that significant metabolism of FDG occurs beyond FDG-6-P in all organs examined and that the extent of this metabolism varies from tissue to tissue (degree of metabolism beyond FDG-6-P, expressed as percentage of total organ FDG content, was brain 45 +/- 3%; heart 29 +/- 2%; liver 22+/-3% and kidney 17 +/- 3%, mean +/- SEM n=6). Furthermore, we demonstrate that the relative accumulation of each metabolite was tissue-dependent and reflected the metabolic and regulatory characteristics of each organ. Such inter-tissue differences may have implications for the mathematical modelling of glucose uptake and phosphorylation using FDG as a glucose tracer.