Biphenotypic B/macrophage cells express COX-1 and up-regulate COX-2 expression and prostaglandin E(2) production in response to pro-inflammatory signals

B/macrophage cells are biphenotypic leukocytes of unknown function that simultaneously express B lymphocyte (IgM, IgD, B220, CD5) and macrophage (phagocytosis, F4/80, Mac-1) characteristics. B/macrophage cells can be generated from purified mouse B lymphocytes incubated in fibroblast-conditioned medium. A potential role for B/macrophage cells in inflammation was shown by their ability to express prostaglandin H synthase-1 (COX-1) and prostaglandin H synthase-2 (COX-2) and by their production of prostaglandin (PG) E(2). COX-1 and COX-2 mRNA expression is not observed in the precursor B lymphocytes and is not known to be a property of B lineage cells. In contrast, COX-2 and the prostanoids PGE(2), PGF(2alpha) and PGD(2) are highly inducible in B/ macrophage cells upon stimulation with lipopolysaccharide, CD40 ligand, or via engagement of surface IgM, supporting a role for these cells in inflammation. PGD(2) and its metabolites are of interest because they activate the nuclear receptor PPARgamma that regulates lipid metabolism. The B/macrophage represents the first instance of a normal B-lineage cell capable of expressing COX-2. Importantly, B/macrophage cells were identified in vivo, providing evidence that they may play a significant role in immune responses. Since PGE(2) blunts IL-12 production, its synthesis by B/macrophage cells may shift the balance of an immune response towards Th2 and humoral immunity.     

Odor cue mediation of alcohol aversion learning in rats lacking gustatory neocortex.

Normal rats presented with a 5% alcohol solution followed by lithium chloride-induced illness quickly learned to avoid drinking alcohol. After training, the rats also avoided drinking water in the presence of the alcohol odor alone, whether tested immediately or 1 month later. In Experiment 1, rats with gustatory neocortex (GN) ablations also developed strong alcohol aversions when the alcohol solution was paired with illness. They also showed normal avoidance of drinking in the presence of the alcohol odor alone when tested soon after training. In Experiment 2, when normal rats were trained to avoid alcohol, given GN ablations, and then tested for retention 1 month later, avoidance of drinking water in the presence of the odor alone was significant but attenuated somewhat in relation to trained control rats. These data support the hypothesis that rats lacking GN partially acquire alcohol aversions by using odor cues and confirm that associative learning is intact in these rats despite the fact that GN rats display significant deficits in aversion learning when only tastes are paired with illness.     

Clinical correlates of index values in the focus HerpeSelect ELISA for antibodies to herpes simplex virus type 2 (HSV-2).

BACKGROUND: Clinical correlates of HerpeSelect ELISA index values are poorly understood. OBJECTIVES: This study was designed to determine the effects of time of infection, test variability, and antibody avidity on index values. STUDY DESIGN: Sera (N=313) from 81 patients with new HSV-2 infections and 236 sera from 32 patients with long-standing (median 11.3 years) HSV-2 were tested by HerpeSelect HSV-2 ELISA. High positive, low positive and negative controls were run on 42 test plates to establish test variability. RESULTS: Index values tended to rise after infection, peaking a median of 9-10 weeks post-infection (range 8-323 days). Of 32 patients with established HSV-2 infections, 7 (22%) had at least one low index value (>1.1 to < or =3.5), and one had a transient seroreversion event. Test variability of index values was substantially lower than inter- or intra-patient variability. Median antibody avidity was higher in sera with high versus low index values in established infections, but unrelated to index value in patients with early infections. CONCLUSIONS: Index values or index value changes are not absolute indicators of early versus established HSV-2 infection or solely a function of test variability. Low antibody avidity may contribute to low index values once infection is established.     

Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo-Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo-Ia difference on such islets, pretreatment of the islets with anti-Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo-Ia antigens can lead to a stronger anti-class I rejection response.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Steady state assumptions in DALYs: effect on estimates of HIV impact

OBJECTIVE: The disability adjusted life year (DALY) and the healthy life year (HeaLY) are both composite indicators of disease burden in a population, which combine healthy life lost from mortality and morbidity. The two formulations deal with the onset and course of a disease differently. The purpose of this paper is to compare the DALY and HeaLY formulations as to differences in apparent impact when a disease is not in an epidemiological steady state and to explore the implications of the differing results. DESIGN: HIV is used as a case study of a major disease that is entering its explosive growth phase in large areas of Asia. Data from the global burden of disease study of the World Bank and World Health Organisation for 1990 has been used to compare burden of disease measures in the two formulations. SETTING: The data pertain to global and regional estimates of HIV impact. RESULTS: The DALY attributes life lost from premature mortality to the year of death, while the HeaLY to the year of disease onset. This results in very large differences in estimates of healthy life lost based upon the DALY construct as compared with the HeaLY, for diseases such as HIV or those with a strong secular trend. CONCLUSION: The demonstration of the dramatic difference between the two indicators of disease burden reflects a limitation of the DALY. This information may directly influence decision making based on such methods and is critical to understand.     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。