Exposure to second hand smoking among middle school students in Beijing in 2019 / 中国学校卫生

Objective@#To understand the exposure to second hand smoking (SHS) and associated factors among middle school students in Beijing, and to provide data support for tobacco control.@*Methods@#The two stage stratified cluster random sampling method were used to select 10 532 students from 370 classes in 48 junior middle schools, 34 senior high schools and 14 vocational high schools in 16 districts of Beijing. The national unified paper questionnaire was used to collect the information.@*Results@#During the past 7 days, 71.5% (95% CI =70.2%-72.7%) of students reported exposure to SHS. The proportion of exposure was highest (60.3%) in outdoor public places, followed by indoor public places (48.9%), at home (34.1%), and public transport (19.1%). About 31.6% of students reported people smoking in the campus in the past 30 days. Risk factors of SHS exposure included one or more parents was smoker( OR =2.62), friends who smoked( OR =2.13), received education on tobacco hazards in school( OR = 0.74 ), and senior high school( OR =0.68-0.73)( P <0.05).@*Conclusion@#High exposure to second hand smoking among middle school students in Beijing is common. Implementation of the regulations and the publicity of tobacco hazards and tobacco control in schools should be strengthened. Smoke free household should be advocated, and middle school students, especially junior middle school students, should be protected from the harm of SHS.

Transmission risk of viruses in large mucosalivary droplets on the surface of objects: A time-based analysis.

The novel human coronavirus SARS-CoV-2 has been responsible for a worldwide pandemic. Although media transmission through contaminated surfaces is one of the most recognized ways of transmission, the study on the number and viability of viruses surviving on a surface after leaving the host represents a "blind spot" in current research. In this paper we have reviewed studies on the physical process of droplet evaporation on media surfaces, and analyzed the recent literature related to experiments on the decay of the viral concentration and infectious activity of SARS-CoV-2 and other viruses on those surface and in the air. The huge differences in the risk of media transmission of large saliva and sputum droplets were analyzed in terms of time elapsed. Due to the rapid decrease of water content in the evaporated droplets and the increased concentration of each component, the living environment of the virus tended to deteriorate sharply, and virus concentration plummeted within a few minutes. Although a virus can be detected in a matter of hours, tens of hours, or days, the risk of transmission is negligible compared to when it first left the host. This study suggests that the key to prevention and control is to start from the source, the earlier the better. It is extremely important to develop good public health habits, wear masks, and wash hands frequently. That said, excessive disinfection and sterilization of surfaces during a later period may have adverse effects.

Qingxin Kaiqiao Fang Inhibits Aß 25-35-Induced Apoptosis in Primary Cultured Rat Hippocampal Neuronal Cells via the p38 MAPK Pathway: An Experimental Validation and Network Pharmacology Study.

Qingxin kaiqiao fang (QKF), a traditional Chinese medicine compound, has been applied to treat Alzheimer's disease (AD) for many years and has exhibited remarkable effects. However, the underlying mechanism is still not explicit. The current study aims to investigate whether QKF exerts an antiapoptotic role through the p38 MAPK pathway in the course of AD. Network pharmacology analysis was applied to study the effective components, possible therapeutic targets, and AD-related pathway of QKF. Further, the AD cell model was established using amyloid-beta (Aß)25-35 peptide and primary hippocampal neuronal cells extracted from newborn Sprague-Dawley rats. Microtubule-associated protein-2 (MAP-2) imaging was used to detect the morphology of hippocampal neurons. Western blot (WB) analysis was applied to detect the protein expression levels of p38 MAPK, p-p38 MAPK, Bcl-2, Bax, caspase-3, and cleaved caspase-3. Cell viability and apoptosis were determined using cell counting kit-8 (CCK-8) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, respectively. SB203580 and U46619 were used to detect changes in cell morphology, cell viability, and apoptosis upon inhibiting or activating p38 MAPK. Our present work showed that QKF protects hippocampal neuronal morphology, enhances cell viability, and reduces the number of TUNEL-positive cells. In addition, our results showed that QKF increased the expression levels of antiapoptotic proteins and decreased the expression of proapoptotic proteins. QKF at 25 mg·mL-1 best inhibited neuronal apoptosis among the three doses of QKF by suppressing p38 MAPK activity. Collectively, QKF plays an antiapoptotic role via the p38 MAPK pathway.

Qingxin Kaiqiao Recipe Improves Cognitive Performance, Inhibits Apoptosis, and Reduces Pathological Deposits in APP/PS1 Double Transgenic Mice via the PI3K/Akt Pathway.

The traditional Chinese medicine of Qingxin Kaiqiao Recipe (QKR) is effective in the treatment of Alzheimer's disease (AD). This study aims to investigate whether QKR improves the cognitive ability and takes neuroprotective effect on APP/PS1 double transgenic mice via the PI3K/Akt pathway. APP/PS1 double transgenic mice were randomly divided into a model, donepezil-treated, or QKR-treated group (L-QKR: 4.75 mg/kg/d, M-QKR: 9.5 mg/kg/d, and H-QKR: 19 mg/kg/d, respectively). Wild-type C57/BL6J mice were used as the control group. Morris water maze (MWM) was used to test the ability of spatial navigation and memorization; terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) assay was applied to test the apoptosis; amyloid protein granule deposition was detected via Methenamine silver staining; Western blot (WB) analysis, immunohistochemistry, and RT-PCR were applied to measure the expression of Aß and corresponding indicators of the PI3K/Akt pathway. Compared with the model group, QKR significantly relieved the cognitive impairment, reduced the deposition of senile plaques, decreased the expression of GSK-3α and Aß, and increased the expression of p-PI3K, p-Akt, and IDE. In addition, the number of TUNEL-positive cells decreased after treatment using QKR. The current study proved that QKR, especially at the high dose tested, exerted a protective effect on improving learning and memory, inhibiting apoptosis, and reducing the process of pathological degeneration in the hippocampus of AD mice.

The impact of anxiety on chronic musculoskeletal pain and the role of astrocyte activation.

Anxiety and depression are associated with increased pain responses in chronic pain states. The extent to which anxiety drives chronic pain, or vice versa, remains an important question that has implications for analgesic treatment strategies. Here, the effect of existing anxiety on future osteoarthritis (OA) pain was investigated, and potential mechanisms were studied in an animal model. Pressure pain detection thresholds, anxiety, and depression were assessed in people with (n = 130) or without (n = 100) painful knee OA. Separately, knee pain and anxiety scores were also measured twice over 12 months in 4730 individuals recruited from the general population. A preclinical investigation of a model of OA pain in normo-anxiety Sprague-Dawley (SD) and high-anxiety Wistar Kyoto (WKY) rats assessed underlying neurobiological mechanisms. Higher anxiety, independently from depression, was associated with significantly lower pressure pain detection thresholds at sites local to (P < 0.01) and distant from (P < 0.05) the painful knee in patients with OA. Separately, high anxiety scores predicted increased risk of knee pain onset in 3274 originally pain-free people over the 1-year period (odds ratio = 1.71; 95% confidence interval = 1.25-2.34, P < 0.00083). Similarly, WKY rats developed significantly lower ipsilateral and contralateral hind paw withdrawal thresholds in the monosodium iodoacetate model of OA pain, compared with SD rats (P = 0.0005). Linear regressions revealed that baseline anxiety-like behaviour was predictive of lowered paw withdrawal thresholds in WKY rats, mirroring the human data. This augmented pain phenotype was significantly associated with increased glial fibrillary acidic protein immunofluorescence in pain-associated brain regions, identifying supraspinal astrocyte activation as a significant mechanism underlying anxiety-augmented pain behaviour.

Counting statistics of photon emissions detected in non-Markovian environment.

In this work we present a large-deviation analysis for the counting statistics of atomic spontaneous emissions continuously detected in finite-bandwidth non-Markovian environment. We show that the statistics of the spontaneous emissions depends on the time interval (τ) of successive detections, which can result in big differences such as dynamical phase transition. This feature excludes the idea of regarding the spontaneous emissions as detection-free objective events. Possible experiment is briefly discussed in connection with the state-of-the-art optical cavity set-up.

Majorana dc Josephson current mediated by a quantum dot.

The Josephson supercurrent through a hybrid Majorana-quantum dot-Majorana junction is investigated. We particularly analyze the effect of spin-selective coupling between the Majorana and quantum dot states, which only emerges in the topological phase and will influence the current through bent junctions and/or in the presence of magnetic fields in the quantum dot. We find that the characteristic behavior of the supercurrent through this system is quite counterintuitive, differing remarkably from the resonant tunneling, e.g. through the similar (normal phase) superconductor-quantum dot-superconductor junction. Our analysis is carried out under the influence of the full set-up parameters and for both the [Formula: see text] and [Formula: see text] periodic currents. The present study is expected to be relevant to the future exploration of applications of Majorana-nanowire circuits.

Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis.

BACKGROUND: Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims of this study were to determine the influence of a passage number on the effects of MSCs on pain behaviour and cartilage and bone features in a rodent model of OA. METHODS: Rats underwent either medial meniscal transection (MNX) or sham surgery under anaesthesia. Rats received intra-articular injection of either 1.5 × 106 late passage MSCs labelled with 10 µg/ml SiMAG, 1.5 × 106 late passage mesenchymal stem cells, the steroid Kenalog (200 µg/20 µL), 1.5 × 106 early passage MSCs, or serum-free media (SFM). Sham-operated rats received intra-articular injection of SFM. Pain behaviour was quantified until day 42 postmodel induction. Magnetic resonance imaging (MRI) was used to localise the labelled cells within the knee joint. RESULTS: Late passage MSCs and Kenalog attenuated established pain behaviour in MNX rats, but did not alter MNX-induced joint pathology at the end of the study period. Early passage MSCs exacerbated MNX-induced pain behaviour for up to one week postinjection and did not alter joint pathology. CONCLUSION: Our data demonstrate for the first time the role of a passage number in influencing the therapeutic effects of MSCs in a model of OA pain.

A mechanistic multicentre, parallel group, randomised placebo-controlled trial of mesalazine for the treatment of IBS with diarrhoea (IBS-D).

INTRODUCTION: Immune activation has been reported in the mucosa of IBS patients with diarrhoea (IBS-D), and some small studies have suggested that mesalazine may reduce symptoms. We performed a double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. METHODS: Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of 'satisfactory relief of IBS symptoms'. RESULTS: 136 patients with IBS-D (82 women, 54 men) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in mesalazine and 2.7 (1.9) in the placebo group with no significant group difference, (95% CI) 0.1 (-0.33 to 0.53), p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared with placebo during the last two-weeks follow-up. CONCLUSIONS: This study does not support any clinically meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. TRIAL REGISTRATION NUMBER: NCT01316718.

Differential Effects of Tacrolimus versus Sirolimus on the Proliferation, Activation and Differentiation of Human B Cells.

The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC) and mTOR inhibitor (Sirolimus, SRL) on B cell activation, differentiation and proliferation is not well documented. Purified human B cells from healthy volunteers were stimulated through the B Cell Receptor with Anti-IgM + anti-CD40 + IL21 in the absence / presence of TAC or SRL. A variety of parameters of B cell activity including activation, differentiation, cytokine productions and proliferation were monitored by flow cytometry. SRL at clinically relevant concentrations (6 ng/ml) profoundly inhibited CD19(+ )B cell proliferation compared to controls whereas TAC at similar concentrations had a minimal effect. CD27(+) memory B cells were affected more by SRL than naïve CD27- B cells. SRL effectively blocked B cell differentiation into plasma cells (CD19(+)CD138(+) and Blimp1(+)/Pax5(low) cells) even at low dose (2 ng/ml), and totally eliminated them at 6 ng/ml. SRL decreased absolute B cell counts, but the residual responding cells acquired an activated phenotype (CD25(+)/CD69(+)) and increased the expression of HLA-DR. SRL-treated stimulated B cells on a per cell basis were able to enhance the proliferation of allogeneic CD4(+)CD25(-) T cells and induce a shift toward the Th1 phenotype. Thus, SRL and TAC have different effects on B lymphocytes. These data may provide insights into the clinical use of these two agents in recipients of solid organ transplants.

Revisit the spin-FET: multiple reflection, inelastic scattering, and lateral size effects.

We revisit the spin-injected field effect transistor (spin-FET) in a framework of the lattice model by applying the recursive lattice Green's function approach. In the one-dimensional case the results of simulations in coherent regime reveal noticeable differences from the celebrated Datta-Das model, which lead us to an improved treatment with generalized result. The simulations also allow us to address inelastic scattering and lateral confinement effects in the control of spins. These issues are very important in the spin-FET device.

Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis.

BACKGROUND: Increased subchondral bone turnover may contribute to pain in osteoarthritis (OA). OBJECTIVES: To investigate the analgesic potential of a modified version of osteoprotegerin (osteoprotegerin-Fc (OPG-Fc)) in the monosodium iodoacetate (MIA) model of OA pain. METHODS: Male Sprague Dawley rats (140-260 g) were treated with either OPG-Fc (3 mg/kg, subcutaneously) or vehicle (phosphate-buffered saline) between days 1 and 27 (pre-emptive treatment) or days 21 and 27 (therapeutic treatment) after an intra-articular injection of MIA (1 mg/50 µl) or saline. A separate cohort of rats received the bisphosphonate zoledronate (100 µg/kg, subcutaneously) between days 1 and 25 post-MIA injection. Incapacitance testing and von Frey (1-15 g) hind paw withdrawal thresholds were used to assess pain behaviour. At the end of the study, rats were killed and the knee joints and spinal cord removed for analysis. Immunohistochemical studies using Iba-1 and GFAP quantified levels of activation of spinal microglia and astrocytes, respectively. Joint sections were stained with haematoxylin and eosin or Safranin-O fast green and scored for matrix proteoglycan and overall joint morphology. The numbers of tartrate-resistant acid phosphatase-positive osteoclasts were quantified. N=10 rats/group. RESULTS: Pre-emptive treatment with OPG-Fc significantly attenuated the development of MIA-induced changes in weightbearing, but not allodynia. OPG-Fc decreased osteoclast number, inhibited the formation of osteophytes and improved structural pathology within the joint similarly to the decrease seen after pretreatment with the bisphosphonate, zoledronate. Therapeutic treatment with OPG-Fc decreased pain behaviour, but did not improve pathology in rats with established joint damage. CONCLUSIONS: Our data suggest that early targeting of osteoclasts may reduce pain associated with OA.

[Clinical significance of ROS1 rearrangements in non-small cell lung cancer].

Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in multiple malignancies, including non-small cell lung cancer (NSCLC). ROS1 rearrangement defines a new molecular subset of NSCLC with the prevalence of ROS1 rearrangements around 1%-2%. ROS1-positive NSCLCs arise in young never-smokers with adenocarcinoma that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib demonstrates in vitro activity and early clinical trial shows marked antitumor activity in ROS1-rearranged patients. The overall response rate is around 56% and the disease control rate at 8 weeks is about 76%. Further understanding the ROS1 fusions in the pathogenesis of NSCLC, methods to detect ROS1 rearrangements, and targeting ROS1-rearranged NSCLC patients with specific kinase inhibitors would lead to an era of personalized medicine.

Common gamma chain cytokines promote rapid in vitro expansion of allo-specific human CD8+ suppressor T cells.

Human CD8(+) regulatory T cells, particularly the CD8(+)CD28(-) T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8(+) T cells which results in significant expansions of donor-specific CD8(+)CD28(-) T suppressor cells in vitro. The expanded CD8(+)CD28(-) T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4(+) T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8(+)CD28(-) T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation.

Apigenin, a dietary flavonoid, sensitizes human T cells for activation-induced cell death by inhibiting PKB/Akt and NF-kappaB activation pathway.

Resistance of T cells to activation-induced cell death (AICD) is associated with autoimmunity and lymphoproliferation. We found that apigenin (4',5,7-trihydroxyflavone), a non-mutagenic dietary flavonoid, augmented both extrinsic and intrinsic pathways of apoptosis in recurrently activated, but not in primarily stimulated, human blood CD4+ T cells. Apigenin potentiated AICD by inhibiting NF-kappaB activation and suppressing NF-kappaB-regulated anti-apoptotic molecules, cFLIP, Bcl-x(L), Mcl-1, XIAP and IAP, but not Bcl-2. Apigenin suppressed NF-kappaB translocation to nucleus and inhibited IkappaBalpha phosphorylation and degradation in response to TCR stimulation in reactivated peripheral blood CD4 T cells, as well as in leukemic Jurkat T cell lines. Among the pathways that lead to NF-kappaB activation upon TCR stimulation, apigenin selectively inhibited PI3K-PKB/Akt, but not PKC-theta activation in the human T cells, and synergized with a PI3K inhibitor to markedly augment AICD. Apigenin also suppressed expression of anti-apoptotic cyclooxygenase 2 (COX-2) protein in activated human T cells, but it did not affect activation of Erk MAPKinase. Thus, in chronically activated human T cells, relatively non-toxic apigenin can suppress anti-apoptotic pathways involving NF-kappaB activation, and especially cFLIP and COX-2 expression that are important for functioning and maintenance of immune cells in inflammation, autoimmunity and lymphoproliferation.

Hyperexpression of cyclooxygenase 2 in the lupus immune system and effect of cyclooxygenase 2 inhibitor diet therapy in a murine model of systemic lupus erythematosus.

OBJECTIVE: To investigate the role of cyclooxygenase 2 (COX-2) in the functioning of different cell types involved in the lupus autoimmune response, and to examine the therapeutic effect of COX-2 inhibitors in mice prone to spontaneously develop systemic lupus erythematosus (SLE). METHODS: Lupus-prone (SWR x NZB)F(1) mice were fed with a diet containing different doses of the COX-2-specific inhibitor celecoxib or the nonspecific inhibitor aspirin, or a combination of both, and the effects of the therapy on autoantibody production, development of lupus nephritis, and mortality were determined. Expression of COX-2 by different cells of the lupus immune system and the effect of COX-2 inhibitors on the function of these cells in vitro and in vivo were assessed. RESULTS: The immune cells of mice with SLE spontaneously hyperexpressed COX-2, and COX-2 inhibitors could cause cell apoptosis. Treatment with COX-2 inhibitors resulted in decreased autoantibody production and inhibition of the T cell response to the major lupus autoantigen, nucleosome, and its presentation by antigen-presenting cells. Surprisingly, a significant increase in survival occurred only in mice receiving intermittent therapy with the lowest dose of celecoxib (500 parts per million), approximating <100 mg of celecoxib/day in humans. A continuous diet, but not intermittent feeding, with the combination of celecoxib and aspirin delayed development of nephritis temporarily, but failed to prolong survival. Indeed, treatment with aspirin alone increased mortality. CONCLUSION: The contributions of the major players in the pathogenic autoimmune response, namely, T cells, B cells, dendritic cells, and macrophages that are abnormally hyperactive in lupus, depend on the increased expression and activity of COX-2, similar to inflammatory cells in target organs. Intermittent pulse therapy with low doses of select COX-2 inhibitors would be of value in the treatment of lupus.

T-helper cell intrinsic defects in lupus that break peripheral tolerance to nuclear autoantigens.

Special populations of T helper cells drive B cells to produce IgG class switched, pathogenic autoantibodies in lupus. The major source of antigenic determinants (epitopes) that trigger interactions between lupus T and B cells is nucleosomes of apoptotic cells. These epitopes can be used for antigen-specific therapy of lupus. Secondly, the autoimmune T cells of lupus are sustained because they resist anergy and activation-induced programmed cell death by markedly upregulating cyclooxygenase (COX) 2 along with the antiapoptotic molecule c-FLIP. Only certain COX-2 inhibitors block pathogenic anti-DNA autoantibody production in lupus by causing death of autoimmune T helper cells. Hence COX-2 inhibitors may work independently of their ability to block the enzymatic function of COX-2, and structural peculiarities of these select inhibitors may lead to better drug discovery and design.

Molecular cloning of a cDNA encoding the porcine type XVII collagen noncollagenous 16 A domain and localization of the domain to the upper part of porcine skin basement membrane zone.

Bullous pemphigoid is an autoimmune blistering human skin disease mediated by immunoglobulin (Ig)G autoantibodies targeting skin basement membrane component type XVII collagen, a transmembrane protein. Also designated BP180 and BPAG2, type XVII collagen is an extracellular matrix element essential for the connection between the epidermis and the underlying dermis. In addition to being a target antigen in the human disease bullous pemphigoid, type XVII collagen is also targeted by autoantibodies of canine, feline, equine and porcine patients suffering from a similar blistering skin disease. Previously, enzyme-linked immunosorbent assay and Western blot analyses have shown that autoantibodies from pigs affected with bullous pemphigoid recognize the human NC16A domain of type XVII collagen. To facilitate the development of porcine model of bullous pemphigoid, we isolated cDNA encoding the porcine type XVII collagen NC16A domain using a reverse transcription-polymerase chain reaction technique. The amino acids deduced from the NC16A cDNA showed 61% identity with the sequence of human NC16A. An antibody generated against a 20-amino acid peptide within the porcine NC16A localized the NC16A epitope to the upper part of porcine skin basement membrane zone. Our data provide further information of the porcine bullous pemphigoid target antigen and may help investigators for their further studies of this disease.

Human lupus T cells resist inactivation and escape death by upregulating COX-2.

Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death receptor (Fas) signaling. However, mutations in the genes encoding Fas and its ligand (FasL) are rare in classical SLE. By gene microarray profiling, validated by functional and biochemical studies, we establish here that activated T cells of lupus patients resist anergy and apoptosis by markedly upregulating and sustaining cyclooxygenase-2 (COX-2) expression. Inhibition of COX-2 caused apoptosis of the anergy-resistant lupus T cells by augmenting Fas signaling and markedly decreasing the survival molecule c-FLIP (cellular homolog of viral FLICE inhibitory protein). Studies with COX-2 inhibitors and Cox-2-deficient mice confirmed that this COX-2/FLIP antiapoptosis program is used selectively by anergy-resistant lupus T cells, and not by cancer cells or other autoimmune T cells. Notably, the gene encoding COX-2 is located in a lupus-susceptibility region on chromosome 1. We also found that only some COX-2 inhibitors were able to suppress the production of pathogenic autoantibodies to DNA by causing autoimmune T-cell apoptosis, an effect that was independent of prostaglandin E(2) (PGE(2)). These findings could be useful in the design of lupus therapies.

B cell stimulatory effects of alpha-enolase that is differentially expressed in NZB mouse B cells.

Intrinsic polyclonal B cell activation is characteristic of NZB mice and it contributes to the development of lupus nephritis in NZB crosses. Although multiple autosomal genes appear to be involved, the major loci for B cell hyperactivity have been mapped on chromosome 4. To identify various genes determining B cell hyperactivity, differential mRNA display was done comparing B cells of NZB and BALB/c mice. The approach yielded 32 genes that were consistently upregulated in NZB B cells. Among these, alpha-enolase, which is located in the region of chromosome 4 containing B cell hyperactivity loci, was found to be spontaneously overexpressed only in NZB B cells, but not in splenic B or T cells of BALB/c or T cells of NZB mice. Exposure to soluble, but not plate-bound, enolase induced splenic B cells from normal BALB/c mice or B cell lymphoma lines to secrete Ig that was mediated by augmented transcription. Moreover, in combination with a subthreshold stimulus with anti-IgM, enolase augmented the expression of CD69 and B7.2 in nai;ve B cells from normal mice. Enolase probably functions intracellularly as an accessory molecule in stimulating B cells. Since functionally related genes tend to congregate, enolase may contribute to polyclonal B cell activation in cooperation with other genes in the hyperactivity loci, which appear to be in a transcriptionally active region in NZB B cells.