Nonhuman primates express human leukemia-associated antigens

Serologic studies using four murine monoclonal antibodies specific for the common acute lymphoblastic leukemia antigen (CALLA) and five monoclonal antibodies specific for the gp24 surface antigen indicate that these leukemia-associated antigens are present on cells of comparable tissues in man and in four nonhuman primates. As in man, adherent cell populations obtained from skin, lung, and bone marrow of Macaca fascicularis, M mulatta, M nemestrina, and Papio cynocephalus react with these antibodies. Similarly, granulocytes from both man and these nonhuman primates bind CALLA- and gp24-specific antibodies. Radioimmune precipitation experiments confirm the identity of these antigens. Our studies suggest that nonhuman primates can be used to screen serologic reagents to leukemia-associated antigens for potential toxic effects on normal tissues prior to their use in man. Similarly, nonhuman primates could be employed to assess the possible role of antigen-positive stromal cells in the reconstitution of bone marrow following transplantation.     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

Survival of donor cells 25 years after intrauterine transfusion

Persistence of donor leukocytes in the circulation of recipients of intrauterine transfusion (IUT) has been observed up to 5 years after birth. The aim of this study was to determine whether transfusions with nonirradiated, nonleukocyte-depleted donor blood during the fetal period resulted in long-term immunomodulation of the recipient. Twenty-four surviving IUT recipients between 1966 and 1976 were tested for autoimmune disease and autoantibodies at follow-up. Ten had sex-mismatched donors and were therefore informative for chimerism studies using fluorescence in situ hybridization (FISH). Seven female recipients could be tested for chimerism using a Y- chromosome-specific polymerase chain reaction (PCR) because they received at least 1 IUT from a male donor. Nine recipients could be studied for cytotoxic T-lymphocyte precursor (CTLp) and helper T-lymphocyte precursor (HTLp) frequencies because the original donors were available for testing. All surviving IUT recipients were in good health at the time of the examination, and routine laboratory testing revealed no abnormalities. None of the IUT recipients were chimeric as determined by FISH analysis, but Y-chromosome-specific sequences were detected by PCR in 6 of the 7 women. However, the CTLp and HTLp frequencies of the IUT recipients against the donors were comparable to those of the controls. The current study provides evidence that IUT can result in the persistence of donor cells in the recipient for a period longer than 20 years but that it is not associated with immunotolerance or with signs of chronic antigenic stimulation. (Blood. 2000;95:2709-2714)     

The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is associated with an increased risk of venous (VTE) and arterial thromboembolism (ATE). Lupus anticoagulant (LA) and anticardiolipin antibodies (ACAs) are established risk factors. We assessed the contribution of deficiencies of antithrombin, protein C, total protein S, factor V Leiden, the prothrombin G20210A mutation and APC resistance, either alone or in various combinations with LA and/or ACAs, to the thrombotic risk in a cohort of 144 consecutive patients with SLE. Median follow-up was 12.7 years. VTE had occurred in 10% and ATE in 11% of patients. LA,ACAs, factor V Leiden, and the prothrombin mutation were identified as risk factors for VTE. Annual incidences of VTE were 2.01 (0.74-4.37) in patients with one of these disorders and 3.05 (0.63-8.93) in patients with 2 disorders. The risk of VTE was 20- and 30-fold higher, respectively, compared with the normal population. In contrast with LA and ACAs, thrombophilic disorders did not influence the risk of ATE. In conclusion, factor V Leiden and the prothrombin mutation contribute to the risk of VTE in patients with SLE, and potentiate this risk when one of these thrombophilic defects are combined with LA and/or ACAs.     

Fatty fish and supplements are the greatest modifiable contributors to the serum 25-hydroxyvitamin D concentration in a multiethnic population

Objective Because vitamin D synthesis is lower in a heavily pigmented skin than in a lighter skin, the relative contribution of determinants to the vitamin D concentration might differ between ethnic groups. The aim of this study was to assess the prevalence of vitamin D deficiency and the relative contribution of vitamin D consumption and exposure to sunlight to the vitamin D concentration in a multiethnic population. Design Cross‐sectional study. Patients A total of 613 adults aged 18–65 years from a random sample from general practices in the Netherlands (52°N, 2003–05), stratified according to gender and ethnic group. Measurements Serum 25‐hydroxyvitamin D [25(OH)D], PTH, ethnic group, sunlight exposure, consumption of foods and supplements rich in vitamin D. Results The prevalence (95% confidence interval) of vitamin D deficiency [serum 25(OH)D < 25 nmol/l] was higher in Turkish (41·3%; 32·5–50·1), Moroccan (36·5%; 26·9–46·1), Surinam South Asian (51·4%; 41·9–60·9), Surinam Creole (45·3%; 34·0–56·6), sub‐Saharan African (19·3%; 9·1–29·5) and other adults (29·1%; 17·1–41·1) compared to the indigenous Dutch (5·9%; 1·3–10·5). Modifiable, significant determinants (standardized regression coefficients) for serum 25(OH)D concentration were: consumption of fatty fish (0·160), use of vitamin D supplements (0·142), area of uncovered skin (highest category 0·136; middle category 0·028), use of tanning bed (0·103), consumption of margarine (0·093) and preference for sun (0·089). We found no significant modification of ethnic group on the effect of sunlight determinants. Conclusion Of the modifiable determinants, fatty fish and supplements are the greatest contributors to the serum 25(OH)D concentration in a multiethnic population.     

卫生应急人员对突发事件风险评估的认知分析

目的 :了解我国卫生应急人员对突发公共卫生事件风险评估的认知状况,从文化程度、职称情况、单位性质、单位级别等方面进行比较,为提高卫生应急人员风险评估的认识和能力提供依据。方法 :采用问卷调查的方法,对全国(大陆地区)31个省(自治区、直辖市)承担突发公共卫生事件应急处置的卫生应急工作人员进行调查。采用描述性分析和χ2检验对调查数据进行分析。结果 :我国卫生应急人员对风险评估概念熟悉程度较低,且不同学历、不同职称、不同工作年限、不同机构、不同层级之间的认知存在一定差异;对风险评估工作内容的认知也存在分歧。结论 :应加强风险评估培训,健全风险评估制度,以全面提高卫生应急人员对风险评估的认知水平。