Influence of graft size matching on outcomes of infantile living donor liver transplantation

We aimed to assess the impact of size mismatching between grafts and recipients on outcomes of infants or small children after LDLT. Between October 2006 and December 2014, 129 LDLT recipients weighing no more than 8 kg were retrospectively analyzed. The entire cohort was categorized into three groups by GRWR: GRWR<3.0% (group A, n = 38), 3.0%≤GRWR<4.0% (group B, n = 61), and GRWR≥4.0% (group C, n = 30). Baseline characteristics were similar among groups A, B, and C. Compared with groups A and B, post‐transplant alanine aminotransferase and aspartate aminotransferase within seven days were significantly higher in group C; however, differences between total bilirubin and albumin after transplantation were not prominent. Moreover, incidences of surgical complications, perioperative deaths, infections, and acute rejections were all comparable among the three groups. Five‐yr patient survival rates for groups A, B, and C were 89.5%, 88.9%, and 81.6%, respectively (p = 0.872), and the graft survival rates were 89.5%, 86.6%, and 81.6%, respectively (p = 0.846). In conclusion, GRWR between 1.9% and 5.8% would not cause noticeable adverse events for infantile LDLT recipients ≤8 kg. However, there is still a role for considering reduction in the graft mass as an applicable strategy in selected cases.     

性激素及人前列腺生长因子对人前列腺间质成纤维细胞增殖的影响

从人胎儿前列腺组织中分离培养了间质成纤维细胞,观察雄激素(DHT)、雌激素(E_2)及部分纯化的人前列腺生长因子(hPGF)对该细胞增殖的影响。结果发现:(1)DHT及hPGF对体外培养的人前列腺间质成纤维细胞均具有明显的促增殖作用,但前者表现为延迟反应,后者为即时效应;(2)雌激素对该细胞无刺激增殖作用;(3)E_2与DHT联合应用对该细胞增殖刺激作用也无明显影响。实验结果提示:DHT对人前列腺间质成纤维细胞具有间接的刺激增殖作用,可能通过刺激前列腺细胞自分泌或旁分泌作用而调节前列腺生长。     

三磷酸腺苷静脉注射诱发快速性心律失常

本研究选择79例阵发性室上性心动过速患者,在窦性心律或诱发的室上性心动过速发作时分级递增静脉注射三磷酸腺苷332次,诱发出窦性心动过速194例次(58.43%)、房性反复搏动34例次(10.24%)、室上性心动过速13例次(3.92%)、偶发房性早搏8例次(2.41%)、阵发性心房颤动3例次(0.9%)和偶发室性早搏2例次(0.6%)。除室上性心动过速外,均为一过性。未引起血液动力学障碍。     

Distinct microRNA expression profiles in acute myeloid leukemia with common translocations

MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific miRNAs may play a role in the development of leukemia with these associated genetic rearrangements.     

Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury

Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptor is present in the lungs, and NMDA receptor antagonist MK-801 attenuates oxidant lung injury. We hypothesized that Glu excitotoxicity may participate in the pathogenesis of hyperoxia-induced lung injury. To determine possible pulmonary protective effects, we administered 0.05 ml/kg MK-801 or saline intraperitoneally daily to neonatal rats exposed to more than 95% oxygen in air. After 7 days, MK-801 decreased the hyperoxia-associated elevation of wet-to-dry lung weight, total leukocyte and neutrophil counts, total protein and lactate dehydroase in BAL fluid, total myeloperoxidase activity, and lung pathological injury. MK-801 inhibited hyperoxia-associated increments in reactive oxygen species production and NF-kappaB production. Hence, NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats, and is associated with decreased reactive oxygen species and NF-kappaB. We conclude that Glu may play an important role in hyperoxia-induced lung injury by activation of NMDA receptor.     

Food allergy and related risk factors in 2540 preschool children: an epidemiological survey in Guangdong Province,southern China

Background

Although the number of studies on allergic diseases in the general population of southern China is increasing, only a few have addressed food allergy (FA) in children in this region. The present study aimed to investigate the prevalence, clinical manifestations, spectrum of allergens, and related risk factors of FA in preschool children in Guangdong Province, southern China.

Methods

A random cluster-sampling method was used to select 24 kindergartens from 12 cities in Guangdong Province. The parents or guardians of the children were requested to complete a questionnaire on general information and data regarding FA diagnosis and symptoms in the children and their first-degree relatives. Thereafter, the Chi-square test, multivariate regression analysis, and Spearman’s rank-order correlation coefficient analysis were performed to identify statistically significant differences.

Results

Analysis of 2540 valid questionnaires revealed an FA prevalence rate of 4%. Adverse food reactions were due to the consumption of shrimp (4.4%), crab (3.2%), mango (2.3%), cow’s milk and dairy products (1.9%), and eggs (1.4%). Logistic regression analysis indicated that a history of FA and a history of allergic rhinitis in the first-degree relatives were the major factors leading to FA in children.

Conclusions

The incidence of FA in children in Guangdong Province is higher than that commonly believed. An individual’s genetic background is an important risk factor for FA. Hence, mitigation of the impact of lifestyle and environmental factors should be carefully considered to reduce the incidence of childhood FA.

     

Chromosomal aberrations in PARP(-/-) mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA

Depletion of poly(ADP-ribose) polymerase (PARP) increases the frequency of recombination, gene amplification, sister chromatid exchanges, and micronuclei formation in cells exposed to genotoxic agents, implicating PARP in the maintenance of genomic stability. Flow cytometric analysis now has revealed an unstable tetraploid population in immortalized fibroblasts derived from PARP(-/-) mice. Comparative genomic hybridization detected partial chromosomal gains in 4C5-ter, 5F-ter, and 14A1-C1 in PARP(-/-)mice and immortalized PARP(-/-)fibroblasts. Neither the chromosomal gains nor the tetraploid population were apparent in PARP(-/-) cells stably transfected with PARP cDNA [PARP(-/-)(+PARP)], indicating negative selection of cells with these genetic aberrations after reintroduction of PARP cDNA. Although the tumor suppressor p53 was not detectable in PARP(-/-) cells, p53 expression was partially restored in PARP(-/-) (+PARP) cells. Loss of 14D3-ter that encompasses the tumor suppressor gene Rb-1 in PARP(-/-) mice was associated with a reduction in retinoblastoma(Rb) expression; increased expression of the oncogene Jun was correlated with a gain in 4C5-ter that harbors this oncogene. These results further implicate PARP in the maintenance of genomic stability and suggest that altered expression of p53, Rb, and Jun, as well as undoubtedly many other proteins may be a result of genomic instability associated with PARP deficiency.     

慢性乙型肝炎和肝病中Fas和FasL表达的原位研究

目的了解慢性乙型肝炎和肝病时介导凋亡的Ｆａｓ／ＦａｓＬ表现。方法以免疫组化法原位检查各种慢性肝病４５例的活检肝组织。结果肝内浸润的淋巴细胞中检出ＦａｓＬ，肝细胞Ｆａｓ／ＦａｓＬ表达与炎症活动性一致，多分布在界面性炎症区。肝细胞表达ＦａｓＬ，可能也发挥细胞毒效应。结论新的发现是ＦａｓＬ可在肝细胞结节和肝癌细胞表达，提示有细胞毒效应的ＦａｓＬ在ＨＢ相关慢性肝病中有发病学意义。肝癌细胞中未检出Ｆａｓ而检出ＦａｓＬ，可能是一种肿瘤逃避免疫攻击的机制     

Transmission of human immunodeficiency virus in a dental practice.

OBJECTIVE: To determine if patients of a dentist with the acquired immunodeficiency syndrome (AIDS) became infected with human immunodeficiency virus (HIV) during their dental care and, if so, to identify possible mechanisms of transmission. DESIGN: Retrospective epidemiologic follow-up of the dentist, his office practice, and his former patients. SETTING: The practice of a dentist with AIDS in Florida. PARTICIPANTS: A dentist with AIDS, his health care providers and employees, and former patients of the dentist, including eight HIV-infected patients. MEASUREMENTS: Identification of risks for HIV transmission (if present), degree of genetic relatedness of the viruses, and identification of infection control and other office practices. RESULTS: Five of the eight HIV-infected patients had no confirmed exposures to HIV other than the dental practice and were infected with HIV strains that were closely related to those of the dentist. Each of the five had invasive dental procedures, done by the dentist after he was diagnosed with AIDS. Four of these five patients shared visit days (P greater than 0.2). Breaches in infection control and other dental office practices to explain these transmissions could not be identified. CONCLUSION: Although the specific incident that resulted in HIV transmission to these patients remains uncertain, the epidemiologic evidence supports direct dentist-to-patient transmission rather than a patient-to-patient route.     

Homeostatic regulation of T follicular helper and antibody response to particle antigens by IL-1Ra of medullary sinus macrophage origin

Hepatitis B virus (HBV) vaccines are composed of surface antigen HBsAg that spontaneously assembles into subviral particles. Factors that impede its humoral immunity in 5% to 10% of vaccinees remain elusive. Here, we showed that the low-level interleukin-1 receptor antagonist (IL-1Ra) can predict antibody protection both in mice and humans. Mechanistically, murine IL-1Ra–inhibited T follicular helper (Tfh) cell expansion and subsequent germinal center (GC)-dependent humoral immunity, resulting in significantly weakened protection against the HBV challenge. Compared to soluble antigens, HBsAg particle antigen displayed a unique capture/uptake and innate immune activation, including IL-1Ra expression, preferably of medullary sinus macrophages. In humans, a unique polymorphism in the RelA/p65 binding site of IL-1Ra enhancer associated IL-1Ra levels with ethnicity-dependent vaccination outcome. Therefore, the differential IL-1Ra response to particle antigens probably creates a suppressive milieu for Tfh/GC development, and neutralization of IL-1Ra would resurrect antibody response in HBV vaccine nonresponders.

Follicular helper T (Tfh) cells are antigen-experienced CD4⁺ T cells within B cell follicles of secondary lymphoid organs, such as lymph nodes (LN), spleens, and Peyer’s patches, that constitutively express the B cell follicle homing receptor CXCR5 (1). Upon cellular interaction and cross-signaling with their cognate follicular B (FoB) cells in the presence of follicular dendritic cells (FDCs), Tfh cells trigger the formation and maintenance of germinal centers (GCs) through the expression of CD40 ligand and the secretion of IL-21 and IL-4 (2–4). Tfh-dependent paracrine activation of CD40 results in B cell survival and differentiation in the GC (5), whereas isotype class switching is believed to occur predominantly outside GCs. Therefore, Tfh cells play a critical role in mediating the selection of high-affinity B cells that differentiate either into plasma cells or memory B cells (6–11).Besides the inducible T cell costimulator (ICOS) that activates Tfh cells to secrete IL-21, other cytokines [e.g., IL-2 (12), IL-6 (13), and IL-7 (14)] also signal for Tfh cell differentiation. The role of IL-1 signaling remained puzzling until recently: Tfh cells can be primed by IL-1β, whose production is licensed by IFN-β in response to infectious agents (15). Such featured innate response of IFN-β and IL-1β relies on the activation of TLR and inflammasomes by live, but not dead, bacteria or recombinant vaccines (16, 17). Therefore, OVA antigen augments Tfh cell response in mice only when IL-1β is exogenously applied at a nonphysiological high concentration (18), whereas endogenous IL-1β/IL-1R1 signaling may not be required for antibody responses to T-dependent or -independent antigens (19–21). We reasoned that IL-1Ra (encoded by IL-1rn), which can compete with IL-1 for binding to IL-1R1 in the homeostatic inflammatory response (22–24), would intrinsically antagonize IL-1β/IL-1R1 signaling for Tfh/GC development. For example, IL-1rn^−/− mice exhibit an excessive antibody response to sheep red blood cells immunization (25, 26). A thorough investigation is required to dissect how IL-1 and IL-1Ra mutually regulate a homeostatic Tfh/GC response.LN macrophages are conventionally divided into two subtypes. Subcapsular sinus (SCS, CD169⁺F4/80⁻) macrophages are specialized antigen presenting cells that capture certain particle or opsonized antigens and display them intact for cognate recognition by FoB cells (27–30). SCS macrophages also relay immune complex to noncognate B cells for antibody affinity maturation (30). Macrophages in medullary sinus (MSM, CD169⁺F4/80⁺), in contrast, are potent in phagocytosis (31) for clearance of pathogens and particulate antigens from the lymph. It has been postulated 10 y ago that SCS may capture particle antigens, such as hepatitis B virus (HBV) vaccine, and migrate to follicles to facilitate more effective activation of B cells and FDCs (32). In this work, we found that murine antibody response inversely correlated to IL-1Ra level and clearly distinguished responders from nonresponders in volunteers receiving HBV vaccination. Further studies showed that LN macrophages subsets exhibited different capture and activation kinetics for particle and soluble antigens, and IL-1Ra expression by MSM could critically modulate IL-1R1 potentiation of Tfh cells and, hence, the specific antibody response to particle antigens. Therefore, mice lacking IL-1Ra or with IL-1Ra being neutralized yielded more robust antibody response to HBV vaccine and enables protection against chronic HBV infection.