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1.
Background
Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment.Methodology/Principal Findings
We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE2 had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients'' plasma. Of note, PGE2, which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype.Conclusion/Significance
Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival. 相似文献2.
Carmen Tur Mar Tintoré ángela Vidal-Jordana Denis Bichuetti Pablo Nieto González María Jesús Arévalo Georgina Arrambide Elisenda Anglada Ingrid Galán Joaquín Castilló Carlos Nos Jordi Río María Isabel Martín Manuel Comabella Jaume Sastre-Garriga Xavier Montalban 《PloS one》2013,8(12)
Objective
We aimed to investigate the ability of natalizumab (NTZ)-treated patients to assume treatment-associated risks and the factors involved in such risk acceptance.Methods
From a total of 185 patients, 114 patients on NTZ as of July 2011 carried out a comprehensive survey. We obtained disease severity perception scores, personality traits’ scores, and risk-acceptance scores (RAS) so that higher RAS indicated higher risk acceptance. We recorded JC virus status (JCV+/-), prior immunosuppression, NTZ treatment duration, and clinical characteristics. NTZ patients were split into subgroups (A-E), depending on their individual PML risk. Some 22 MS patients on first-line drugs (DMD) acted as controls.Results
No differences between treatment groups were observed in disease severity perception and personality traits. RAS were higher in NTZ than in DMD patients (p<0.01). Perception of the own disease as a more severe condition tended to predict higher RAS (p=0.07). Higher neuroticism scores predicted higher RAS in the NTZ group as a whole (p=0.04), and in high PML-risk subgroups (A-B) (p=0.02). In low PML-risk subgroups (C-E), higher RAS were associated with a JCV+ status (p=0.01). Neither disability scores nor pre-treatment relapse rate predicted RAS in either group.Conclusions
Risk acceptance is a multifactorial phenomenon, which might be partly explained by an adaptive process, in light of the higher risk acceptance amongst NTZ-treated patients and, especially, amongst those who are JCV seropositive but still have low PML risk, but which seems also intimately related to personality traits. 相似文献3.
Andrew J. Solomon William Hills Zunqiu Chen James Rosenbaum Dennis Bourdette Ruth Whitham 《PloS one》2013,8(6)
Background
Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.Objectives
To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren’s Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren’s Syndrome.Methods
Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.Results
Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren’s Syndrome.Conclusions
Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease. 相似文献4.
Background
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease. It is thought to be mediated by CD4+ Th1/Th17 cells. More recently, cells of the innate immune system such as dendritic cells (DCs) and natural killer (NK) cells have been in focus. Glatiramer acetate (GA) is an approved drug for treating MS patients.Methodology/Principal Findings
In the current study we examined the activities of NK and DCs in nine relapsing remitting MS patients for up to one year after initiation of GA treatment. We observed that NK cells isolated from most of these patients have increased cytotoxic activity against K562 cells. Further analysis showed that the same NK cells lysed both autologous immature (i) and mature (m) DCs. In most patients this increased activity was correlated with increased NK cell activating cytotoxicity receptors such as NKp30, NKp44, NKp46 and NKG2D, and reduced expression of the inhibitory molecule CD158 on the surface of these NK cells. The expression of HLA-DR was increased on iDCs and mDCs in the majority of the patients, but no consistency was observed for the expression of HLA-I or HLA-E. Also, the co-stimulatory receptors CD80, CD83 or CD86 expression was down-regulated on iDCs and mDCs in most cases. Further, the expression of CCR6 was increased on mDCs at later time points of therapy (between 32–48 weeks).Conclusions/Significance
Our results are the first showing the effects of GA treatment on NK cells in MS patients, which may impact future use of this and other drugs to treat this disease. 相似文献5.
Background
Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti-tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression.Methodology/Principal Findings
We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells.Conclusions/Significance
This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs. 相似文献6.
Iaffaldano P Viterbo RG Paolicelli D Lucchese G Portaccio E Goretti B Direnzo V D'Onghia M Zoccolella S Amato MP Trojano M 《PloS one》2012,7(4):e35843
Background and Objectives
Natalizumab reduces the relapse rate and magnetic resonance imaging activity in patients with Relapsing-Remitting Multiple Sclerosis (RRMS). So far the influence of natalizumab on cognitive functions and fatigue in MS remains uncertain. The aim of this prospective, open-label, observational study was to evaluate the possible effects of natalizumab on cognition and fatigue measures in RRMS patients treated for up to two years.Methods
Cognitive performances were examined by the Rao''s Brief Repeatable Battery (BRB), the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months. Patients who failed in at least 3 tests of the BRB and the ST were classified as cognitively impaired (CI). Fatigue Severity Scale (FSS) was administered every 12 months to assess patient''s self-reported fatigue. One hundred and 53 patients completed 1 and 2 year-natalizumab treatment, respectively.Results
After 1 year of treatment the percentage of CI patients decreased from 29% (29/100) at baseline to 19% (19/100) (p = 0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p = 0.008). These significant effects were confirmed in the subgroup of patients treated up to two years.Conclusions
These results demonstrate that a short-term NTZ treatment may significantly improve cognitive performances and fatigue in RRMS patients. 相似文献7.
Background
Stimulation of CD137 ligand on human monocytes has been shown to induce DC differentiation, and these CD137L-DCs are more potent than classical DCs, in stimulating T cell responses in vitro. To allow an in vivo evaluation of the potency of CD137L-DCs in murine models we aimed at generating murine CD137L-DCs.Methodology/Principal Findings
When stimulated through CD137 ligand murine monocytes responded just as human monocytes with an increased adherence, morphological changes, proliferation and an increase in viable cell numbers. But CD137 ligand signaling did not induce expression of inflammatory cytokines and costimulatory molecules in murine monocytes and these cells had no T cell stimulatory activity. Murine monocytes did not differentiate to inflammatory DCs upon CD137 ligand signaling. Furthermore, while CD137 ligand signaling induces maturation of human immature classical DCs it failed to do so with murine immature classical DCs.Conclusions/Significance
These data demonstrate that both human and murine monocytes become activated by CD137 ligand signaling but only human and not murine monocytes differentiate to inflammatory DCs. 相似文献8.
Background
Multiple sclerosis (MS) is less common in Asia, including Taiwan, and some characteristics of MS in Asians differ from those of Caucasians. Tumefactive brain lesion is even rarer in MS patients.Objective
To review patients with tumefactive MS and compare them with those in other studies investigating tumefactive demyelinating lesions and our Taiwanese typical MS patients.Methods
Twelve patients (6.3%) from the 190 MS patients visiting Taipei Veterans General Hospital from 1985 to 2010 were enrolled. They all fulfilled the McDonald or Poser criteria for MS and had at least one brain lesion larger than 2 centimeters with or without a mass effect.Results
Eleven patients (91.7%) were female and presented tumefactive brain lesions during the first attack. The clinical course of all patients was relapsing-remitting with a second attack within 2 years. Their initial extended disability status score was higher, but the prognosis was better after more than 2 years of follow-up, than in other studies. Moreover, our patients did not have optic or spinal involvement as well as positive neuromyelitis optica immunoglobulin or aquaporin-4 antibody, which is very common in Taiwanese MS patients.Conclusion
Tumefactive MS is not common in Taiwan. Although the tumefactive demyelinating lesions seem to be terrible initially, their prognosis is relatively more favorable than expected. 相似文献9.
Maria Letizia Giardino Torchia Elena Ciaglia Anna Maria Masci Laura Vitiello Manuela Fogli Andrea la Sala Domenico Mavilio Luigi Racioppi 《PloS one》2010,5(6)
Background
HIV-1 Protease Inhibitors, namely PIs, originally designed to inhibit HIV-1 aspartic protease, can modulate the immune response by mechanisms largely unknown, and independent from their activity on viral replication. Here, we analyzed the ability of PIs to interfere with differentiation program of monocytes toward dendritic cell (DCs) lineage, a key process in the inflammatory response.Methodology/Principal Findings
Monocytes from healthy donors were isolated and induced to differentiate in vitro in the presence or absence of saquinavir, ritonavir, nelfinavir, indinavir or amprenavir (sqv, rtv, nlfv, idv, apv, respectively). These drugs demonstrated a differential ability to sustain the generation of immature DCs (iDCs) with an altered phenotype, including low levels of CD1a, CD86, CD36 and CD209. DCs generated in the presence of rtv also failed to acquire the typical phenotype of mature DCs (mDCs), and secreted lower amounts of IL-12 and IL-15. Accordingly, these aberrant mDCs failed to support activation of autologous Natural Killer (NK) cells, and resulted highly susceptible to NK cell-mediated cytotoxicity.Conclusions/Significance
Our findings uncover novel functional properties of PIs within the DC-NK cell cross-talk, unveiling the heterogeneous ability of members of this class drugs to drive the generation of atypical monocyte-derived DCs (MDDCs) showing an aberrant phenotype, a failure to respond appropriately to bacterial endotoxin, a weak ability to prime autologous NK cells, and a high susceptibility to NK cell killing. These unexpected properties might contribute to limit inflammation and viral spreading in HIV-1 infected patients under PIs treatment, and open novel therapeutical perspectives for this class drugs as immunomodulators in autoimmunity and cancer. 相似文献10.
Background
HIV-1 has evolved ways to exploit DCs, thereby facilitating viral dissemination and allowing evasion of antiviral immunity. Recently, the fate of DCs has been found to be extremely dependent on the interaction with autologous NK cells, but the mechanisms by which NK-DC interaction controls viral infections remain unclear. Here, we investigate the impact of NK-DC cross-talk on maturation and functions of HIV-infected immature DCs.Methodology/Principal Findings
Immature DCs were derived from primary monocytes, cultured in the presence of IL-4 and GM-CSF. In some experiments, DCs were infected with R5-HIV-1BaL or X4-HIV-1NDK, and viral replication, proviral HIV-DNA and the frequency of infected DCs were measured. Autologous NK cells were sorted and either kept unstimulated in the presence of suboptimal concentration of IL-2, or activated by a combination of PHA and IL-2. The impact of 24 h NK-DC cross-talk on the fate of HIV-1-infected DCs was analyzed. We report that activated NK cells were required for the induction of maturation of DCs, whether uninfected or HIV-1-infected, and this process involved HMGB1. However, the cross-talk between HIV-1-infected DCs and activated NK cells was functionally defective, as demonstrated by the strong impairment of DCs to induce Th1 polarization of naïve CD4 T cells. This was associated with the defective production of IL-12 and IL-18 by infected DCs. Moreover, the crosstalk between activated NK cells and HIV-infected DCs resulted in a dramatic increase in viral replication and proviral DNA expression in DCs. HMGB1, produced both by NK cells and DCs, was found to play a pivotal role in this process, and inhibition of HMGB1 activity by glycyrrhizin, known to bind specifically to HMGB1, or blocking anti-HMGB1 antibodies, abrogated NK-dependent HIV-1 replication in DCs.Conclusion
These observations provide evidence for the crucial role of NK-DC cross-talk in promoting viral dissemination, and challenge the question of the in vivo involvement of HMGB1 in the triggering of HIV-1 replication and replenishment of viral reservoirs in AIDS. 相似文献11.
Background
Many patients with chronic kidney disease (CKD) suffer from fatigue caused by anemia, but that anemia can be reversed. Successful treatment can be measured as a decrease in fatigue and an increase in energy or vitality, particularly on the vitality (VT) subscale of the SF-36. Changes in VT scores are most commonly interpreted in terms of minimally important differences or standardized effect sizes, but neither a minimally important difference nor a standardized effect size provides information about how patients’ activities are affected. Therefore, we analyzed the association between differences in VT scores and a variable that is meaningful to patients and to society the frequency of going out.Study Design
Questionnaire survey. Analyses of differences among participants at bseline, and analyses of differences within participants over time.Setting and Participants
CKD patients who were not on dialysis and were involved in a study of anti-anemia therapy.Predictor
VT scores.Outcome
Frequency of going out.Measurements
VT scores and the frequency of going out.Results
At baseline, higher VT scores and younger age were associated with going out more often, while sex and the presence of diabetic nephropathy were not associated with the frequency of going out. Greater changes in VT scores over time were associated with greater changes in the frequency of going out, in univariate and multivariate analyses.Conclusions
At baseline, VT was associated with the frequency of going out. Increases in VT were also associated with increases in the frequency of going out. These results show how VT scores can be linked to daily activities that are important to individual patients and to society. 相似文献12.
Chris P. Verschoor Jennie Johnstone Jamie Millar Robin Parsons Alina Lelic Mark Loeb Jonathan L. Bramson Dawn M. E. Bowdish 《PloS one》2014,9(8)
Background
Circulating myeloid cells are important mediators of the inflammatory response, acting as a major source of resident tissue antigen presenting cells and serum cytokines. They represent a number of distinct subpopulations whose functional capacity and relative concentrations are known to change with age. Little is known of these changes in the very old and physically frail, a rapidly increasing proportion of the North American population.Design
In the following study the frequency and receptor expression of blood monocytes and dendritic cells (DCs) were characterized in a sample of advanced-age, frail elderly (81–100 yrs), and compared against that of adults (19–59 yrs), and community-dwelling seniors (61–76 yrs). Cytokine responses following TLR stimulation were also investigated, as well as associations between immunophenotyping parameters and chronic diseases.Results
The advanced-age, frail elderly had significantly fewer CD14(++) and CD14(+)CD16(+), but not CD14(++)CD16(+) monocytes, fewer plasmacytoid and myeloid DCs, and a lower frequency of monocytes expressing the chemokine receptors CCR2 and CX3CR1. At baseline and following stimulation with TLR-2 and -4 agonists, monocytes from the advanced-age, frail elderly produced more TNF than adults, although the overall induction was significantly lower. Finally, monocyte subset frequency and CX3CR1 expression was positively associated with dementia, while negatively associated with anemia and diabetes in the advanced-age, frail elderly.Conclusions
These data demonstrate that blood monocyte frequency and phenotype are altered in the advanced-age, frail elderly and that these changes correlate with certain chronic diseases. Whether these changes contribute to or are caused by these conditions warrants further investigation. 相似文献13.
Paul Stoll Martin Ulrich Kai Bratke Katharina Garbe J Christian Virchow Marek Lommatzsch 《Respiratory research》2015,16(1)
Background
Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.Methods
Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.Results
Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.Conclusion
An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users. 相似文献14.
J Howard M Battaglini JS Babb D Arienzo B Holst M Omari N De Stefano J Herbert M Inglese 《PloS one》2012,7(8):e43061
Objectives
Multiple sclerosis (MS) in African-Americans (AAs) is characterized by more rapid disease progression and poorer response to treatment than in Caucasian-Americans (CAs). MRI provides useful and non-invasive tools to investigate the pathological substrate of clinical progression. The aim of our study was to compare MRI measures of brain damage between AAs and CAs with MS.Methods
Retrospective analysis of 97 AAs and 97 CAs with MS matched for age, gender, disease duration and age at MRI examination.Results
AA patients had significantly greater T2- (p = 0.001) and T1-weighted (p = 0.0003) lesion volumes compared to CA patients. In contrast, measurements of global and regional brain volume did not significantly differ between the two ethnic groups (p>0.1).Conclusions
By studying a quite large sample of well demographically and clinically matched CA and AA patients with a homogeneous MRI protocol we showed that higher lesion accumulation, rather than pronounced brain volume decrease might explain the early progress to ambulatory assistance of AAs with MS. 相似文献15.
Background
Dendritic cells capture antigens through PRRs and modulate adaptive immune responses. The type of adaptive immune T cell response generated is dependent upon the type of PRR activated by the microbes. Dectin-1 is a C-type lectin receptor present on dendritic cells.Methodology/Principal Findings
Here we show that selective dectin-1 agonist Curdlan can activate human DCs and induce the secretion of large amounts of IL-23, IL-1β, IL-6 and low levels of IL-12p70 as determined by ELISA. The Curdlan-stimulated DCs are efficient at priming naïve CD4 cells to differentiate into Th17 and Th1 cells. Furthermore, these CD4 T cells induce differentiation of B cells to secrete IgG and IgA. In addition, Curdlan-stimulated DCs promote the expansion and differentiation of Granzyme and perforin expressing cytotoxic T lymphocyte that display high cytolytic activity against target tumor cells in vitro.Conclusions/Significance
These data demonstrate that DCs stimulated through Dectin-1 can generate efficient Th, CTL and B cell responses and can therefore be used as effective mucosal and systemic adjuvants in humans. 相似文献16.
Doralina Guimar?es Brum Marcelo Rizzatti Luizon Ant?nio Carlos Santos Marco Aurélio Lana-Peixoto Cristiane Franklin Rocha Maria Lucia Brito Enedina Maria Lobato de Oliveira Denis Bernardi Bichuetti Alberto Alan Gabbai Denise Sisterolli Diniz Damacio Ramon Kaimen-Maciel Elizabeth Regina Comini-Frota Claudia E. Vieira Wiezel Yara Costa Netto Muniz Roberta Martins da Silva Costa Celso Teixeira Mendes-Junior Eduardo Ant?nio Donadi Amilton Antunes Barreira Aguinaldo Luiz Sim?es 《PloS one》2013,8(3)
Background
Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients.Methods
Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP).Principal Findings
European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population.Conclusions
Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil. 相似文献17.
FS Lichtenegger K Mueller B Otte B Beck W Hiddemann DJ Schendel M Subklewe 《PloS one》2012,7(9):e44266
Background
Dendritic cells (DCs) determine the activation and polarization of T cells via expression of costimulatory molecules and secretion of cytokines. The function of DCs derived from monocytes ex vivo strongly depends on the composition of the maturation cocktail used.Methodology/Principal Findings
We analyzed the effect of costimulatory molecule expression and cytokine secretion by DCs on T and natural killer (NK) cell activation by conducting a head-to-head comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard combination of proinflammatory cytokines or IL-10 alone. We could show that TLR-induced DCs are characterized by a predominance of costimulatory over coinhibitory molecules and by high secretion of IL-12p70, but not IL-10. Functionally, these signals translated into an increase in IFN-γ secreting Th1 cells and a decrease in regulatory T cells. T cell activation and polarization were dependent on IL-12p70 and CD86, but remarkably not on CD80 signaling. By means of IL-12p70 secretion, only TLR-induced DCs activated NK cells.Conclusions/Significance
TLR-matured DCs are highly suitable for application in immunotherapeutic strategies that rely on strong type 1 polarization and NK cell activation. Their effects particularly depend on high CD86 expression and IL-12p70 secretion. 相似文献18.
Background
The evaluation of mortality of pyroclastic surges and flows (PDCs) produced by explosive eruptions is a major goal in risk assessment and mitigation, particularly in distal reaches of flows that are often heavily urbanized. Pompeii and the nearby archaeological sites preserve the most complete set of evidence of the 79 AD catastrophic eruption recording its effects on structures and people.Methodology/Principal Findings
Here we investigate the causes of mortality in PDCs at Pompeii and surroundings on the bases of a multidisciplinary volcanological and bio-anthropological study. Field and laboratory study of the eruption products and victims merged with numerical simulations and experiments indicate that heat was the main cause of death of people, heretofore supposed to have died by ash suffocation. Our results show that exposure to at least 250°C hot surges at a distance of 10 kilometres from the vent was sufficient to cause instant death, even if people were sheltered within buildings. Despite the fact that impact force and exposure time to dusty gas declined toward PDCs periphery up to the survival conditions, lethal temperatures were maintained up to the PDCs extreme depositional limits.Conclusions/Significance
This evidence indicates that the risk in flow marginal zones could be underestimated by simply assuming that very thin distal deposits, resulting from PDCs with poor total particle load, correspond to negligible effects. Therefore our findings are essential for hazard plans development and for actions aimed to risk mitigation at Vesuvius and other explosive volcanoes. 相似文献19.
Background
Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS).Objectives
To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS.Methods
Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed.Results
Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral.Conclusions
Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases. 相似文献20.
Francesca Rossi Antonio Giorgio Marco Battaglini Maria Laura Stromillo Emilio Portaccio Benedetta Goretti Antonio Federico Bahia Hakiki Maria Pia Amato Nicola De Stefano 《PloS one》2012,7(11)