The Janus Face of Neutrophil Specific Antigen CD177 in Bacterial Infection: Focal Disease Versus Systemic Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1108-1108
Author(s):  
Behnaz Bayat ◽  
Vanessa Santoso ◽  
Beate Kehrel ◽  
Ulrich J Sachs ◽  
Sentot Santoso

Abstract Abstract 1108 CD177, also known as NB1 (or HNA-2) is a GPI-linked glycoprotein, which is exclusively expressed on neutrophils. Approximately 3 to 5% of healthy individuals do not express this antigen on their neutrophils (NBnull). Recent data demonstrated a strong upregulation of NB1 on neutrophils in patients with bacterial, but not viral infections. The mechanism underlying this phenomenon, however, is unknown. Our previous studies showed that NB1 functions as a partner of endothelial PECAM-1 and therefore plays a role on neutrophil diapedesis. Consequently, neutrophils carrying NB1 (NB1plus) migrate faster through endothelial cells than NBnull neutrophils. However, several studies have documented an abrogation of neutrophil migratory abilities in sepsis conditions. In this study, we aim to clarify the impact of neutrophil NB1 expression in bacterial sepsis. To mimic this condition in vitro, we first compared the transendothelial migration ability of NB1 phenotyped neutrophils after stimulation with the bacterial peptide fMLP in a transwell system. Lower transmigration ability (75% vs. 40%) was observed in fMLP-treated NB1plus neutrophils (n = 5) in comparison to untreated neutrophils. In contrast, no significant difference in the migration ability was observed between fMLP-treated and untreated NB1null neutrophils (n = 3). Expression analysis by flow cytometry showed a dose-dependent upregulation of NB1 after stimulation with fMLP (10−6 to 10−8 μM) in NB1plus neutrophils. Interestingly, down regulation of PECAM-1 expression was observed in these treated cells. Contrary, no PECAM-1 downregulation was detected in NBnull fMLP-treated neutrophils. These results could be confirmed by immunoblotting analysis using specific antibodies directed against different epitopes on NB1 (mabs 7D8, MEM166) and against different PECAM-1 Ig domains (mabs PECAM1.1, 1.2 and 1.3). Analysis of the supernatants of fMLP-treated neutrophils demonstrated the shedding of PECAM-1 from NB1plus, but not from NB1null neutrophils. These results indicate that shedding of PECAM-1 from neutrophils during bacterial infections depends on NB1 expression. Recent studies showed that a single nucleotide polymorphism (42C>G) located in NB1 promoter region is associated with the regulation of NB1 expression. Individuals homozygous for C allele express high NB1 surface density in comparison to individuals homozygous for G allele. Our association study showed higher frequency of C allele in patients with bacterial sepsis (n=98) compared with healthy cohort (n = 132) (8.16% vs. 12.88%; P<0.03). This observation indicates the role of C42 allele (or high NB1 expression) as genetic risk factor for bacterial sepsis. All together, these data demonstrate a reverse role of NB1 expression in focal and systemic infection, indicating favourable effect of low NB1 in systemic bacterial infection. This phenomenon may be caused by reduction of neutrophil directionality and motility due to NB1-mediated PECAM-1 shedding. Disclosures: No relevant conflicts of interest to declare.

2020 ◽  
Vol 4 (s1) ◽  
pp. 147-147
Author(s):  
Chloe Getrajdman ◽  
Matthew Sison ◽  
Hung-Mo Lin ◽  
Daniel Katz

OBJECTIVES/GOALS: Little is known about the effect of hemodilution with crystalloid on blood coagulation in obstetric patients. The purpose of our study was to examine the impact of hemodilution on components of blood coagulation using rotational thromboelastometry (ROTEM®) in term parturients METHODS/STUDY POPULATION: This is a prospective, observational pilot study including 35 healthy, pregnant patients at term (≥37 weeks) without history of bleeding or clotting disorder or on medication affecting coagulation. Venous blood samples were collected from all patients and divided into specimen tubes to generate varying degrees of hemodilution with Plasma-Lyte (0%, 20%, 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%). Rotational thromboelastometry was then performed on samples to assess for coagulation changes. RESULTS/ANTICIPATED RESULTS: EXTEM (extrinsically activated assay) clotting time (CT) became prolonged at 65% hemodilution and above, and the median CT was in the coagulopathic range (>80 seconds) at a dilution of 80%. FIBTEM (extrinsically activated assay with platelet inhibitor, primarily measuring contribution of fibrinogen to coagulation) amplitude at 5 minutes (A5) began to diminish at 35% hemodilution, with the median A5 in the coagulopathic range (<12 mm) at 55% hemodilution. The area under the curve (AUC), a marker of clot strength, for EXTEM and FIBTEM consistently declined as hemodilution increased. Greater decreases in FIBTEM AUC were seen compared to EXTEM AUC, with the ratio of FIBTEM:EXTEM AUC at each dilution demonstrating a statistically significant difference from baseline. DISCUSSION/SIGNIFICANCE OF IMPACT: All thromboelastometry values demonstrated a hypocoagulable trend as hemodilution increased. However, the samples analyzed by the FIBTEM assay trended toward a coagulopathy at a lower degree of hemodilution compared to the EXTEM assay. As FIBTEM tests analyze the role of fibrinogen in hemostasis and EXTEM tests analyze the role of platelets, our findings suggest that platelets may be able to withstand higher degrees of hemodilution before impairing hemostasis compared to fibrinogen. These findings support the growing body of literature that in early stages of severe obstetric hemorrhage, the prioritization of fibrinogen replacement may be critical in preventing further coagulopathy. CONFLICT OF INTEREST DESCRIPTION: All authors have no conflicts of interest to report.


Author(s):  
Giuseppe Lisco ◽  
Vito A. Giagulli ◽  
Giovanni De Pergola ◽  
Anna De Tullio ◽  
Edoardo Guastamacchia ◽  
...  

Background: The novel pandemic of Coronavirus disease 2019 (COVID-19) has becoming a public health issue since March 2020 considering that more than 30 million people were found to be infected worldwide. Particularly, recent evidences suggested that men may be considered as at higher risk of poor prognosis or death once the infection occurred and concerns surfaced in regard of the risk of a possible testicular injury due to SARS-CoV-2 infection. Results: Several data support the existence of a bivalent role of testosterone (T) in driving poor prognosis in patients with COVID-19. On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2). At the same time, younger man with normal testicular function compared to women of similar age are prone to develop a blunted immune response against SARS-CoV-2, being exposed to less viral clearance and more viral shedding and systemic spread of the disease. Conversely, low levels of serum T observed in hypogonadal men predispose them to a greater background systemic inflammation, cardiovascular and metabolic diseases, and immune system dysfunction, hence driving harmful consequences once SARS-CoV-2 infection occurred. Finally, SARS-CoV-2, as a systemic disease, may also affect testicles with possible concerns for current and future testicular efficiency. Preliminary data suggested that SARS-CoV-2 genome is not normally found in gonads and gametes, therefore sex transmission could be excluded as a possible way to spread the COVID-19. Conclusion: Most data support a role of T as a bivalent risk factor for poor prognosis (high/normal in younger; lower in elderly) in COVID-19. However, the impact of medical treatment aimed to modify T homeostasis for improving the prognosis of affected patients is unknown in this clinical setting. In addition, testicular damage may be a harmful consequence of the infection even in case it occurred asymptomatically but no long-term evidences are currently available to confirm and quantify this phenomenon. Different authors excluded the presence of SARS-CoV-2 in sperm and oocytes, thus limiting worries about both a potential sexual and gamete-to-embryos transmission of COVID-19. Despite these evidence, long-term and well-designed studies are needed to clarify these issues.


2015 ◽  
Vol 87 (3) ◽  
pp. 238
Author(s):  
Hassan El-Tatawy ◽  
Tarek Gameel ◽  
Mohammed Abo El-enen ◽  
Ayman Hagras ◽  
Ayman Mousa ◽  
...  

Objectives: To evaluate the impact of the prostatic-urethral angulation (PUA) on the treatment efficacy of selective alpha-1A receptor blocker in male patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Materials and methods: A total of 80 patients with LUTS/BPH and with mean age 53.3 ± 6.3 (range 47-70) were included in our prospective comparative study. The patients were classified into 2 groups as a consecutive cases 40 in each one depending on the PUA either ≤ 35° (group A) or &gt; 35° (group B). PUA and different prostatic parameters were measured using transrectal ultrasound. Prostate-specific antigen (PSA), the International Prostate Symptom Score and quality of life score (IPSS/QoL score), maximum flow rate (Q<sub>max</sub>), and postvoid residual (PVR) volume were compared between the groups. The clinical significance of PUA was evaluated after 8 weeks of medical treatment with tamsulosin hydrochloride 0.4 mg daily. Results: Baseline evaluation (pre-treatment) for both groups were comparable to each other with no clinically significant difference regarding age, PSA, IPSS/QoL score, Qmax and PVR volume (P-value &gt; 0.05). Comparison of parameters after 8 weeks showed that tamsulosin hydrochloride improved the total IPSS and all subscores (P &lt; 0.001), QoL (P = 0.001), Q<sub>max</sub> (P = 0.002), and PVR (P = 0.04) in group A (Table 1). Conclusion: Tamsulosin hydrochloride appears to be less effective in improving IPSS/Qol score, Qmax and PVR in patients with lager PUA. The PUA might be a predictor for the treatment efficacy of α-blockers and more studies are warranted in the future before the final conclusion.


2017 ◽  
Vol 46 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Xin Zhao ◽  
Yan-nian Liao ◽  
Qian Huang

Objective To evaluate the impact of inhibition of the receptor for advanced glycation end products (RAGE) on the outcome of bacterial sepsis in animal models. Methods Relevant publications were identified by systematic searches of PubMed, ISI Web of Science and Elsevier-Scopus databases. Results A total of Eleven studies with moderate quality were selected for analysis. A meta-analysis of survival rates revealed a significant advantage of RAGE inhibition in comparison with controls (HR 0.67, 95% CI 0.52–0.86). This effect was most pronounced in polymicrobial infection (HR 0.28, 95% CI 0.14–0.55), followed by Gram positive (G+) bacterial infection (HR 0.70, 95% CI 0.50–0.97) and Gram negative (G−) bacterial infection (HR 0.89, 95% CI 0.58–1.38). For G+ bacterial infection, RAGE inhibition decreased bacterial outgrowth and dissemination, inflammatory cell influx, plasma cytokine levels, and pulmonary injury. Conclusions RAGE inhibition appears to have a beneficial impact on the outcome of sepsis in animal models, although there are discrepancies between different types of infection.


Reproduction ◽  
2015 ◽  
Vol 149 (5) ◽  
pp. 403-411 ◽  
Author(s):  
S Al-Samerria ◽  
I Al-Ali ◽  
J R McFarlane ◽  
G Almahbobi

The primordial follicle reserve is the corner stone of female fertility and determines the longevity and quality of reproduction. Complete depletion of this reserve will lead to primary infertility, and the key-limiting step of follicle depletion is the transition from primordial to primary follicles. It has been reported that this process is gonadotrophin-independent, but other conflicting reports are indicated otherwise and this discrepancy needs to be unequivocally clarified. The aim of this study was to investigate the role of bone morphogenetic proteins (BMPs) in the regulation of folliculogenesis in mice passively immunised against BMP receptor 1B (BMPRIB) and BMP4. While a stereological study revealed that the numbers of primordial follicles in immunised mice were significantly higher when compared with control animals, treatment with equine chorionic gonadotrophin showed no effect. In parallel, immunofluorescence microscopy revealed the presence of BMPRIB but not FSH receptor in primordial follicles. The number of primary follicles in immunised mice were also significantly increased when compared with control animals. After puberty, the rates of depletion of primordial and primary follicles were increased with age, particularly in treated animals; however, there was no significant difference between the treatment groups of the same age. Based on these results together with our previous reports in sheep and mice, we confirm that the attenuation of BMP signalling system can be an effective approach to sustain the primordial follicle reserve while promoting the development of growing follicles, ovulation and consequently overall female fertility.


2020 ◽  
Vol 4 ◽  
pp. 239821282093946
Author(s):  
Maneesh V. Kuruvilla ◽  
David I. G. Wilson ◽  
James A. Ainge

During navigation, landmark processing is critical either for generating an allocentric-based cognitive map or in facilitating egocentric-based strategies. Increasing evidence from manipulation and single-unit recording studies has highlighted the role of the entorhinal cortex in processing landmarks. In particular, the lateral (LEC) and medial (MEC) sub-regions of the entorhinal cortex have been shown to attend to proximal and distal landmarks, respectively. Recent studies have identified a further dissociation in cue processing between the LEC and MEC based on spatial frames of reference. Neurons in the LEC preferentially encode egocentric cues while those in the MEC encode allocentric cues. In this study, we assessed the impact of disrupting the LEC on landmark-based spatial memory in both egocentric and allocentric reference frames. Animals that received excitotoxic lesions of the LEC were significantly impaired, relative to controls, on both egocentric and allocentric versions of an object–place association task. Notably, LEC lesioned animals performed at chance on the egocentric version but above chance on the allocentric version. There was no significant difference in performance between the two groups on an object recognition and spatial T-maze task. Taken together, these results indicate that the LEC plays a role in feature integration more broadly and in specifically processing spatial information within an egocentric reference frame.


2014 ◽  
Vol 121 (6) ◽  
pp. 1354-1358 ◽  
Author(s):  
Ralph Rahme ◽  
Sharon D. Yeatts ◽  
Todd A. Abruzzo ◽  
Lincoln Jimenez ◽  
Liqiong Fan ◽  
...  

Object The role of endovascular therapy in patients with acute ischemic stroke and a solitary M2 occlusion remains unclear. Through a pooled analysis of 3 interventional stroke trials, the authors sought to analyze the impact of successful early reperfusion of M2 occlusions on patient outcome. Methods Patients with a solitary M2 occlusion were identified from the Prolyse in Acute Cerebral Thromboembolism (PROACT) II, Interventional Management of Stroke (IMS), and IMS II trial databases and were divided into 2 groups: successful reperfusion (thrombolysis in cerebral infarction [TICI] 2–3) at 2 hours and failed reperfusion (TICI 0–1) at 2 hours. Baseline characteristics and clinical outcomes were compared. Results Sixty-three patients, 40 from PROACT II and 23 from IMS and IMS II, were identified. Successful early angiographic reperfusion (TICI 2–3) was observed in 31 patients (49.2%). No statistically significant difference in the rates of intracerebral hemorrhage (60.9% vs 47.6%, p = 0.55) or mortality (19.4% vs 15.6%, p = 0.75) was observed. However, there was a trend toward higher incidence of symptomatic hemorrhage in the TICI 2–3 group (17.4% vs 0%, p = 0.11). There was also a trend toward higher baseline glucose levels in this group (151.5 mg/dl vs 129.6 mg/ dl, p = 0.09). Despite these differences, the rate of functional independence (modified Rankin Scale Score 0–2) at 3 months was similar (TICI 2–3, 58.1% vs TICI 0–1, 53.1%; p = 0.80). Conclusions A positive correlation between successful early reperfusion and clinical outcome could not be demonstrated for patients with M2 occlusion. Irrespective of reperfusion status, such patients have better outcomes than those with more proximal occlusions, with more than 50% achieving functional independence at 3 months.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Seung-Jae Lee ◽  
Sam-Sae Oh ◽  
Dal-Soo Lim ◽  
Suk-Keun Hong ◽  
Rak-Kyeong Choi ◽  
...  

Background. The use of anticoagulant therapy (ACT) in patients with acute infective endocarditis (IE) remains a controversial issue. Our study attempts to estimate the impact of ACT on the occurrence of embolic complications and the usefulness of ACT in the prevention of embolism in IE patients.Methods. The present authors analyzed 150 patients with left-sided IE. Embolisms including cerebrovascular events (CVE) and the use of ACT were checked at the time of admission and during hospitalization.Results. 57 patients (38.0%) experienced an embolic event. There was no significant difference in the incidence of CVE and in-hospital mortality between patients with and without warfarin use at admission, although warfarin-naïve patients were significantly more likely to have large (>1 cm) and mobile vegetation. In addition, there was no significant difference in the incidence of postadmission embolism and in-hospital death between patients with and without in-hospital ACT. On multivariate logistic regression analysis, ACT at admission was not significantly associated with a lower risk of embolism in patients with IE.Conclusions. The role of ACT in the prevention of embolism was limited in IE patients undergoing antibiotic therapy, although it seems to reduce the embolic potential of septic vegetation before treatment.


2015 ◽  
Vol 7 (3) ◽  
pp. 292-312 ◽  
Author(s):  
Devika Vashisht ◽  
Sreejesh S

Purpose – The purpose of this paper is to explore the effect of brand placement strength on gamers’ brand recall as moderated by gamers’ prior game playing experience and game involvement in the context of advergames. Specifically, this research utilizes Limited Capacity Model of attention to explain how and under what conditions brand placements create attention, elaboration and subsequent brand recall. Design/methodology/approach – A 2 (brand placement strength: prominent versus subtle) × 2 (prior game playing experience: experienced versus inexperienced) × 2 (game involvement: high versus low involvement) between-subjects measures design is used. Empirical data were obtained from 220 undergraduate student gamers. A between-subjects measures ANOVA is used to test the hypotheses. Findings – There are several important findings that can be inferred from the results. First, inexperienced gamers report high brand recall in prominent brand placements than subtle brand placements, whereas for experienced gamers, no significant difference in recall rates is found between prominent brand placement and subtle brand placement. Second, inexperienced gamers with low game involvement playing an advergame with prominent brand placement report high brand recall compared to inexperienced gamers with high game involvement playing an advergame with prominent brand placement. Research limitations/implications – The study contributes to the advertising literature from a non-traditional advertising perspective, particularly in the context of online advergames, and explains the role of brand placement and its boundary conditions to create customers’ brand memory. Moreover, this research contributes to the marketing knowledge on how to locate and embed the brands effectively in advergames, taking into account the individual characteristics of each advergame. Practical implications – The findings are very important for advertising practitioners because selecting media that enhances the brand memory of the consumers through entertainment is a planning strategy that has been widely used by media planners today. Hence, advertising managers should think about designing advergames by taking into account the game involvement factor to make sure that the implementation has the strongest positive effect on consumers’ memory. Originality/value – This research contributes to the literature of online advertising, especially the advergames by exploring the impact of brand placement strength and prior gaming experience on gamers’ brand recall. In addition, this study is the first step toward understanding the moderating role of game involvement on Indian gamers recall in the context of online advertising.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1159-1159
Author(s):  
Haowen Xiao ◽  
Xiaoyu Lai ◽  
Gongqiang Wu ◽  
Yi Luo ◽  
Jimin Shi ◽  
...  

Abstract Abstract 1159 Poster Board I-181 Background In allogeneic SCT, genetic factors such as donor and recipient gene polymorphisms of pro- and anti-inflammatory cytokines have been associated with the incidence and severity of GVHD. However, the influence of such donor and recipient gene polymorphisms on other outcomes, such as early infection after SCT, has seldom been described. TNFαa, TNF receptorII (TNFRII), IL-10 and TGF gene contain multiple single nucleotide polymorphisms (SNPs) in the promoter and codon region. We thus studied the association of this panel of candidate gene polymorphisms with the incidence of the first episodes of early bacterial infections within 100 days after allo-HSCT. Methods A total of 138 unrelated donor/recipient pairs, who had undergone HLA-matched allo-HSCT from January 2001 to March 2009 at the First Affiliated Hospital of Zhejiang University School of Medicine, were tested for TNFαa(TNFαa-857 C>T, TNFαa-863 C>A, TNFαa-1031 T>C), TNFRII (codon196 T>G), IL-10 (IL10-1082 A>G, IL10-819 T>C, IL10-592 A>C), TGF (TGF-509 T>C, TGF+869 C>T) polymorphism allele frequencies and genotype. SNPs were analysed by Multiplex SnaPshot. We considered the first episodes of early bacterial infections within 100 days after allo-HSCT have developed when sepsis, pneumonia, or septic shock was diagnosed according to previously published criteria. Results (1) 133 patients achieved complete donor chimerism in the peripheral blood and 5 patients had graft failure. All patients achieved an absolute neutrophil count (ANC) greater than 0.5×109/L at day 13 (7∼22) and platelet recovery at day 15 (7∼64). The cumulative incidence of at least one bacterial infection was 47.8% (pneumonia and intestinal infection are the most popular) within 100 days after allo-HSCT. There is no significant difference in the time to neutrophil recovery in patients who experienced early bacterial infections with those who did not (13.6 vs 12.8,P=0.115). (2) The TNFαa-857 C/C genotype and TNFRII 196 T/T genotype of the donor were significantly associated with a higher risk of early bacterial infection ( for TNFαa-857 C/C genotype: 53.3% vs 29.0%, P=0.024 ; TNFRII 196 T/T genotype: 53.5% vs 33.3%, P=0.038); (3) The TGF-509 T/T genotype of the donor was significantly associated with a higher risk of early bacterial infection (62.5% vs 41.8, P=0.038); (4) Transplantation from donors with IL10-819 C/C genotype or IL10-592 C/C genotype were significantly associated with a higher risk of early bacterial infection (for IL10-819 C/C genotype: 71.4.1% vs 45.3%, P=0.034; IL10-592 C/C genotype: 70.0.1% vs 45.8%, P=0.055); (5) The genotypes of TNFαa-863, TNFαa-1031, IL10-1082 and TGF+869 were not found to be associated with the risk of early bacterial infection. Conclusions Recent studies have shown that the generation potential of IL-10 is influenced by the polymorphism of the IL-10 gene. The IL10-819*C allele and IL10-592 *C allele are associated with higher secretion of IL-10 than IL10-819*T allele and IL10-592*A allele. In our data, a higher risk of early bacterial infection with IL10-819 C/C and IL10-592 C/C genotype was postulated to be associated with a higher IL-10 production, which suppressed reactive T-cell response. These results, which is the first report of TNFαa, TNFRII, IL-10and TGF polymorphic features of Chinese population with the risk of early bacterial infection after HLA-matched unrelated allo-HSCT, suggest an interaction of the donor TNFαa-857C/C, TNFRII 196 T/T, IL10-819 C/C, IL10-592 C/C and TGF-509 T/T genotypes on risk of early infection. These results are helpful for predict allo-HSCT outcome, identify more suitable donors and clarify therapy on an individual patient basis. Disclosures No relevant conflicts of interest to declare.


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