Tidal volume (VT) was 7 mL/kg and respiratory frequency (f) was twelve breaths per minute. A five-centimeter H2O PEEP was maintained and 10,000 U of Heparin i.v. (Sanofi-Aventis, Ploërmel, France) was administered. The pigs were killed using pentobarbital i.v. (Chemische Fabrik, Berg, Germany) (25 mg/kg) and potassium chloride i.v. (5 g). Pneumoplegia was performed by infusing 1 L of the preservation fluid

Perfadex® (Vitrolife AB, Gothenburg, Sweden) at 4°C in the right ventricule. Perfadex® was buffered with Trometamol (Addex-THAM, Kabi, Sweden). Finally, the lungs were extracted and stored in a cold room at 4°C for 30 minutes. The usefulness of EVLP Cobimetinib mw is well known and described in literature [7, 12, 17, 43]. Many parameters of our ex vivo preparation was performed in a “state of the art” EVLP setting and published by research teams that are experts in the field [36]. In our experiments, our purpose was not to demonstrate or suggest an evolution of the EVLP technique, but rather to use such experimental preparations to evaluate the benefit of the CsA to reduce IRI. The ex CP-673451 mouse vivo lung function assessment system was primed with 2.8 L of Perfadex® added with 5% of bovine serum albumin (Sigma-Aldrich, St. Louis, MO, USA), and 2 mg/L of Trinitrine (Sanofi-Aventis). The pulmonary artery was cannulated with a 20-F cannula (Turemo,

Ann Arbor, MI, USA) connected to the extracorporeal circuit. A pressure probe (Baxter, Uden, Holland) was first placed into the pulmonary artery, then a temperature probe (Sorin Group, Arvada, CO, USA) was connected to the membrane oxygenator; finally, a second temperature probe (Integral Process, Conflans Sainte Honorine, France) was placed at the pulmonary vein exit. During the rewarming

phase, 2 L/min of oxygen and 2 L/min of nitrogen (93%) mixed with carbon dioxide (7%) were carried to the membrane oxygenator. Isotonic trometamol was used to obtain a physiologic pH in the mixed solution. The rewarming of the lung preparations was initiated by a slow infusion (100 mL/min) at 25°C. The peristaltic pump flow was gradually increased along with the temperature of the perfusion fluid. At 32°C, ventilation was started (VT = 50 mL, f = 12/min, find more PEEP = 5 cmH2O, FiO2 = 50%) and then gradually increased by increments of 20 mL up to a maximal VT of 7 mL/kg. During this rewarming phase, the pump flow was progressively increased up to 1.3 L/min (normal cardiac output for a 20 kg pig). However, PAP was never allowed to exceed 25 mmHg. The pump flow was fixed with a lower pressure less than 25 mmHg in order to preserve the integrity of the capillary-alveolar membrane. The rewarming phase was considered complete when the temperature of the solution from the pulmonary veins reached 36°C, while full cardiac output and ventilation were also obtained.

Transformation efficiency was calculated as number of transformants

μL-1 of plasmid DNA (Patwardhan et al., 2008). An API assay identified 44 isolates obtained from urine samples as A. baumannii and three as Acinetobacter lwoffii, while urinary catheter samples yielded three A. baumannii isolates. CSH indices for all the 50 isolates of Acinetobacter obtained from UTI and urinary catheters were determined Daporinad and they varied from 34% to 79.4%. Nine strains had an HI value between 30% and 40%; six isolates displayed HI values between 41% and 50%; for seven isolates the HI values were between 51% and 60%. For the majority of the strains (22), the HI values varied between 61% and 70%. The six strains of A. baumannii (A1, A2, A3, A4, A5 and A6) that showed the highest hydrophobicity indices are listed in Table 1. Six isolates with the lowest HI values (A45–A50) were also selected. Escherichia coli HB101 and P. aeruginosa PA01 were used as the negative and positive control cultures, respectively. The difference between SRT1720 cost the six strains with the highest HI values and six with the lowest HI values was found to be significantly different with P<0.05. Twenty isolates displayed lectin activity while the remaining 30 did not. A1–A6 produced lectins and A45–A50 did not. Figure 1a shows the HI values of the six strains that produced lectins and displayed the highest HI values (A1, A2, A3, A4, A5 and

A6). These values were compared with those strains that had the lowest HI indices and did not produce lectins (designated as A45, A46, A47, A48, A49 and A50). Standard lectin (phytohemagglutinin) displayed hemagglutination, while normal saline and uninoculated

LB used as negative controls did not show any reaction. The biofilm formation abilities of all the 50 isolates were determined. Quantitative analysis of biofilms formed by A. baumannii on glass and polypropylene surfaces showed that shaking conditions were suitable for biofilm formation. The biofilm formation Vitamin B12 by strains of Acinetobacter with high hydrophobicity (A1–A6) was higher and significant difference was observed compared to strains to low hydrophobicity (A45–A50) with less biofilm-forming ability with P<0.001 (Fig. 1b). Adhesion of A. baumannii on polypropylene was higher than on glass surfaces (Fig. 2). Figure 1 depicts biofilm formation by a representative A. baumannii isolate (A3). The biofilm formation by P. aeruginosa PAO1 was found to be similar to that of A. baumannii, while E. coli was ineffective in forming biofilms on these surfaces (results not shown). Biofilms of six A. baumannii isolates were formed optimally at 30 °C, at pH 7.0 and when supplemented with 5.0 g L−1 NaCl. The results of A. baumannii A3 were shown as a representative isolate. Light microscopic examination of biofilm-forming A. baumannii cells attached to the polycarbonate and glass surfaces were performed and quantified with crystal violet.

2a,b), supports this hypothesis. In migrating neutrophils, eosinophils, fibroblasts,

and MDCK-F cells, it has been demonstrated that increases in [Ca2+]i were localized to the rear part of the cells [23]. Calcium-activated K+ channels localized to the rear part of the cell play an important role in cell migration since it has been shown that the migratory activity of MDCK-F cells was sensitive to the inhibition of KCa3.1 [23]. Accordingly, as shown in the present study the LPS-induced global cell swelling, Ca2+ accumulation and migration were reduced in KCa3.1-deficient BMDCs when compared to WT DCs (Fig. 2) suggesting that LPS-induced migration of DCs might involve the activation of KCa3.1. However, as we mentioned above, we cannot exclude that LPS-induced DC swelling occurs independently Maraviroc order of DC migration. We observed that the reduction of LPS-induced swelling at early time points was only moderate in

KCa3.1-deficient BMDCs (Fig. 2a) when compared to TLR4-deficient BMDCs (Fig. 1a). In DC, it has been demonstrated previously that LPS induces cell swelling by transient activation of the Na+/H+ exchanger [13]. Hence, in KCa3.1-deficient BMDCs an LPS/TLR4-induced activation of the Na+/H+ exchanger operating in parallel to the Cl−/HCO3 exchanger might occur leading to the entry of NaCl together with osmotically obliged water [19]. As shown in Figure 2c, the baseline migratory activity of non-unstimulated KCa3.1-deficient selleck chemical BMDCs was comparatively high when compared to WT DCs. We assumed that possible differences in cell size could be causative for this phenomenon. Analysis

of the forward scatter as a measure of cell size of non-stimulated BMDCs revealed an enhanced cell size of KCa3.1-deficient DCs when compared to WT DCs (data not shown) which might contribute to the high migratory activity of KCa3.1-deficient DCs. In order to test whether the altered migratory capacities resulted from changes in the expression of CCR7, WT and KCa3.1-deficient BMDCs were analyzed by flow tuclazepam cytometry. CCR7 expression on WT and KCa3.1−/− DCs kept in medium for 4 hr was 18.1 ± 6.1 and 21.8 ± 8.2%, respectively (data not shown). Treatment with LPS (500 ng/mL) for 4 hr caused an increase in CCR7 expression in both cell types (27.2 ± 2.8 and 34.0 ± 3.0%, respectively) (data not shown). Altogether, expression of CCR7 by unstimulated and stimulated DCs was slightly enhanced in KCa3.1-deficient cells when compared to WT DCs. Hence, although CCR7 in part might contribute to DC migration, factors other than CCR7 expression like possible compensating activities of other ion channels could be causative for the high migratory activity of untreated KCa3.1−/− DCs (Fig. 2c). Moreover, since the CCR7 expression on KCa3.1−/− DCs was enhanced after LPS treatment, the low migratory activity of these cells (Fig. 2c) cannot be attributed to the changes in CCR7 expression.

In addition, the increased levels of IL-17 and IL-23 suggest that the disturbance of TAO is involved with mechanisms of autoimmunity. Thus, the discovery of IL-17 and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of TAO, which was based previously on the T helper type 1 (Th1)–Th2 paradigm. Thromboangiitis obliterans (TAO), or Buerger’s disease, often leads to vascular insufficiency. It is characterized by chronic inflammation and acute thrombosis Epigenetics inhibitor of small- and medium-calibre arm and leg arteries. The most affected arteries are tibial and radial, with extension to the

veins and nerves of the extremities

[1–4]. A reaction to the constituents of tobacco cigarettes is recognized as a factor in the initiation, progression and prognosis of TAO. Genetic modifications, or autoimmune disorders, are essential aetiological factors [5–7]. Peripheral endothelium-dependent vasodilatation is impaired Enzalutamide nmr in the non-diseased limb of TAO patients, and this vascular dysfunction may contribute to segmental proliferative injury or thrombus formation in peripheral vessels [8]. The immune system seems to play a critical role in the aetiology of TAO. However, knowledge of the immunological aspects involved in the progression of vascular tissue inflammation, and hence the pathophysiology of this disease, is still limited. Abnormalities in immunoreactivity are believed to drive the inflammatory process. Patients with thromboangiitis obliterans have been shown to have increased cellular immunity to types I and III collagen when compared

with patients who have atherosclerosis [4,9]. In addition, high titres of anti-endothelial cell antibodies have been detected in patients with this disorder [10]. Otherwise, cytokines studies involving TAO patients are relatively scarce. Cytokines are small soluble mediators released by various immune cell subsets and tissues, and have a particularly critical role in modulating both the innate and adaptive immune responses. Both a deficiency and an excess of cytokine production, as well as unusual responsiveness of immune cells to cytokines, selleck chemicals can favour the development of immune-mediated disease, suggesting the constant requirement of a fine balance among cytokines to support immune homeostasis. Adaptive immunity has two responses: (i) a humoral immune response by stimulating B lymphocytes to produce antibodies and (ii) a cellular immune response, where CD8+ T cells with cytotoxic and macrophages are activated. CD4+ lymphocytes participate in both responses by antigen recognition and their subsequent differentiation into effector T helper type 1 (Th1) or Th2 subsets.

As shown in Fig. 5A, TLR ligands, TNF or CD40L had a variable effect on MoDC differentiation by day 2 and none of the stimuli led to a substantial increase in apoptosis. Ligation of TLR2 by zymosan, or HKSA and the TLR7/8 ligand CL075, led to the retention of high CD14 expression on a subset of cells and blocked CD1a expression. Other signals, however, did not have a major impact on MoDC differentiation markers despite their ability to decrease the sensitivity to further activation (Fig. 1). Monocyte activation may thus prevent DC differentiation

in the case of some particular TLR ligands; however, such effect does not fully overlap with the tolerizing ability of the different stimuli. In order to identify which TLR-induced signaling pathways Anti-infection Compound Library are impaired in MoDCs that received an early LPS stimulation selleck inhibitor we

studied MAPK, NF-κB and IRF-3 activations in these cells. Activation of MAPKs is attributed to signals transmitted by the Myd88-dependent arm of the TLR pathways that might be particularly affected by the downmodulation of IRAK-1. Accordingly, LPS-induced phosphorylation of the Erk1/2 and p38 kinases, as well as phosphorylation of CREB/ATF-1 transcription factors, often occurring via p38 activation, were abrogated by LPS pre-treatment of developing MoDCs (Fig. 5B). On the contrary, DCs differentiating in the absence of LPS responded readily with Erk1/2, p38 and CREB/ATF-1 phosphorylation to LPS stimulation. The primary step of NF-κB activation is the phosphorylation-dependent degradation of the IκB components, a prerequisite for NF-κB nuclear translocation 29. Interestingly, LPS-induced IκBα phosphorylation occurred similarly in LPS pre-treated and control MoDCs and we did not detect a different level of the total IκBα protein in these

samples either (Fig. 5C). These results indicate that NF-κB might be activated by TLR-dependent signals in LPS-tolerized MoDCs. Further activity of NF-κB is tuned by enzymatic modifications that Carbohydrate include phosphorylation at multiple residues. The NF-κB subunit p65 is phosphorylated at S276 in order to gain strong transcriptional activity, whereas its functions are further modulated by phosphorylations at other sites of the protein 30. We found a similar S276 and S536 phophorylation in response to LPS in both LPS pre-treated and control MoDCs (Fig. 5C). S529 phosphorylation was, on the other hand, inhibited in LPS-pretreated DCs, indicating a partial impairment of NF-κB regulation following persistent LPS signals. However, functional significance of S529 phosphorylation is not known. The partial activation of NF-κB in spite of the decreased Myd88-dependent signal transduction might indicate functional MyD88-independent, TRIF-dependent signal routes. Indeed, we found a strong IRF-3 phosphorylation in response to TLR3 or TLR4 ligation by poly(I:C) and LPS, respectively, in both LPS-pretreated and control MoDCs (Fig. 5D). IRF-3 phosphorylation was rather elevated in LPS–pre-treated cells (3.8- and 2.

pullorum. This organism was first described in 1994 GPCR Compound Library ic50 after clinically derived CLO isolates were examined by various methods, and within 387 samples, six strains of H. pullorum were identified (including NCTC 12826, NCTC 12827, UB3166, UB3659) all associated with gastrointestinal

illness (Burnens et al., 1994; Stanley et al., 1994). One of the patients was a 27-year-old man with diarrhoea, 30 kg weight loss and deranged liver enzymes. No gastrointestinal histology or clinical progress was reported on this case; hence, the similarity of his disease to IBD cannot be commented upon further. One patient was HIV-positive. Helicobacter pullorum (NCTC 13155) has also been associated with diarrhoeal illness in humans in a German study describing two cases with diarrhoea (without blood), one of whom also had common variable immunodeficiency (Steinbrueckner et al., 1997). Both cases apparently resolved spontaneously. The first (immunosuppressed) case was treated once asymptomatic with roxythromycin after which stools were negative for H.

pullorum; however, the second case continued to have positive stools and went on to have a second episode of diarrhoeal illness during which the organism was again cultured. This suggests the possibility of chronic carrier status. Interestingly, in one case, the organism was first identified as C. jejuni/coli based on its Y-27632 molecular weight appearance, growth conditions and oxidase/catalase tests. As we shall see, standard laboratory methods of identification may underestimate the burden of lower gastrointestinal Helicobacter (and indeed novel Campylobacter) disease. One study has potentially contradicted the possibility of H. pullorum being a pathogenic agent resulting in diarrhoeal disease in humans. The work of Ceelen

et al. (2005) examined 531 stool samples from patients with gastroenteritis alongside stool from 100 healthy individuals by H. pullorum-specific PCR. This study demonstrated a strikingly similar prevalence within the two cohorts. The gastroenteritis group were PCR-positive for H. pullorum in 4.3% of cases and the controls in 4.0%. The authors rightly state that DNA positivity may come from ingested foodstuffs and that it does not necessarily infer replication of the organisms within the gastrointestinal tract. Other possibilities explored included a Aspartate variable pathogenicity within the organisms themselves or variable host factors (which may include immunodeficiency or genetic susceptibility). The PCR primers designed by Stanley et al. (1994), which were apparently utilized in this study, have since been revised (Fox et al., 2000). It is not clear what effect, if any, this may have had on the prevalence data provided by the work of Ceelen. The pathogenicity of H. pullorum was recently studied in vitro by Varon et al. (2009) utilizing human gastric (AGS) and intestinal (CaCo-2 and HT-29) epithelial cell lines.

iNKT cells represent a lipid-responsive arm

of the innate immune system that has been implicated in the regulation or promotion of a variety of immune, infectious and neoplastic processes. Invariant natural killer T cells are partially activated at baseline, with stores of both Th1 and Th2 cytokines (e.g. IFN-γ and IL-4, respectively) that can be rapidly secreted [3, 4]. Consistent with this wide-ranging capacity, iNKT cells have been implicated in playing beneficial pro-inflammatory roles (e.g. cancer immunity), deleterious pro-inflammatory roles (e.g. atherosclerosis) and anti-inflammatory roles [e.g. non-alcoholic fatty liver disease (NAFLD), see more graft-versus-host disease (GVHD)] [3, 5, 6]. We have studied iNKT cells in contact sensitivity (CS), also known as contact hypersensitivity or allergic contact dermatitis. CS is a local immune inflammatory response in the skin that occurs following topical exposure to a chemically reactive hapten allergen that covalently binds to self-peptides [7]. Sensitization typically occurs with first exposure to a concentrated dose of hapten,

while elicitation of a profound local inflammatory response may be provoked with subsequent exposure (i.e. challenge) to the same hapten at a much lower dose than required for sensitization. Poison ivy and nickel sensitivity are clinical examples. We have previously described hepatic iNKT cells to be amongst the earliest immune responders following sensitization. As early as 7 min after sensitization, hepatic iNKT cells release IL-4 that binds to Selleckchem Regorafenib IL-4R on peritoneal B-1 B cells, which concurrently receive a second signal via surface B cell receptors of hapten conjugated to circulating self-peptides [8–10]. B-1 B cells are stimulated via Stat-6 signalling to migrate from the peritoneal cavity to the spleen within 24 h to produce antigen-specific IgM antibodies [8, 11]. Meanwhile, naïve T cells are primed via exposure to hapten conjugated to self-peptide that is presented on MHC complexes

by antigen-presenting cells (APC) in the draining lymph nodes of the sensitization site. Upon subsequent exposure, B-1 B cell-generated IgM antibodies bind allergen and then activate complement, triggering mast cells and platelets to locally release Megestrol Acetate vasoactive mediators (serotonin and TNF-α), thereby ultimately enabling local recruitment of primed T cells into the tissues [12–23]. It is an open question of how iNKT cells respond so rapidly to sensitization. The rapidity may be explained by the finding that at baseline, iNKT cells are already partially activated, constitutively expressing IL-4 and IFN-γ [4], likely the result of prior TCR interactions with complexes of self-glycolipids bound within CD1d molecules of APCs. Whether the hepatic lipids that stimulate iNKT cells change in character following sensitization is unknown.

We found that colonic epithelial cells from pIgR KO mice differentially expressed (more than twofold change) more than 200 genes compared with cells from WT mice, and Mitomycin C cost upregulated the expression of antimicrobial peptides in a commensal-dependent manner. Detailed profiling of microbial communities based on 16S rRNA genes revealed differences in the commensal microbiota between pIgR KO and WT mice. Furthermore, we found that pIgR KO mice showed increased susceptibility to dextran sulfate sodium-induced

colitis, and that this was driven by their conventional intestinal microbiota. Thus, in the absence of pIgR, the stability of the commensal microbiota is disturbed, gut homeostasis is compromised, and the outcome of colitis is significantly worsened. Mucus membranes lining the gastrointestinal tract are constantly bombarded by an enormous number of foreign antigens derived from dietary products HM781-36B cell line and the commensal microbiota. The microbial load of the human colon (about 1014 bacteria) is estimated to be more than ten times the number of eukaryotic cells in the body [1, 2]. The commensal microbiota lives in a mutualistic relationship with their host and provides several benefits. These include the digestion of insoluble fibers and increased energy usage of foods, synthesis of vitamin K [3, 4], and niche occupation that could otherwise

be exploited by pathogens [5]. The aggregate gene pool of the microbiota, a.k.a. the metagenome, contains 150 times more genes than the

human genome [6, 7]. Although the human microbiome varies considerably between hosts, our core microbiome has been classified into only three types of communities termed enterotypes [8]. A first line of immune defense mediated by nonspecific innate immune effector components has evolved to protect the epithelial barrier without causing inflammatory immune responses [9]. The primary effector component of the adaptive immune system at mucosal sites is secretory IgA (SIgA) [10]. These antibodies are generated by cooperation between dimeric IgA (dIgA)-producing plasma cells and mucosal epithelial crotamiton cells (ECs), which actively transport dIgA antibodies to the lumen by polymeric Ig receptor (pIgR)-mediated transfer. During transcytosis, the extracellular domain of the pIgR, known as secretory component, becomes covalently coupled to the IgA molecule and final release of receptor–cargo complex occurs by endoproteolytic cleavage of the pIgR [11]. Normally, 80% of the body’s plasma cells are located in the gut and most of these produce dIgA [10]. Germ-free mice, however, have an immature immune system with a greatly reduced number of IgA-producing plasma cells and T cells in the intestinal lamina propria [4]. Upon colonization of germ-free mice with conventional nonpathogenic intestinal bacteria, both T-cell responses and IgA production is activated in the gut.

S6b–e). In addition, B cell subsets developing in the NSG–BLT mice were compared to the populations in human blood. As described previously, there are higher PXD101 levels of immature and transitional B cells in the blood of NSG–BLT mice compared

to humans [37]. Together, these results suggest that irradiation is not necessary for B cell development but is required to obtain optimal number of B cells and for Ig production. We next evaluated the development of human innate immune cells in the BLT model established with or without irradiation conditioning (Supporting information, Fig. S7). The gating strategy used to define the human innate immune subsets is shown in Supporting information, Fig. S7a. At 16 weeks post-implant the development of human monocyte/macrophage (CD14+/CD33+), myeloid dendritic cells (mDC, CD11c+/CD33+) and plasmacytoid DC (pDC, CD123+/CD33+)

was assessed in the blood, spleen and bone marrow (Supporting information, Fig. S7b–d). Significantly higher percentages of human monocyte/macrophage were detected in the blood of NSG–BLT mice that had received irradiation compared to non-irradiated NSG–BLT mice, and there was a trend towards increased levels in the spleen and bone marrow, although these differences Talazoparib in vivo were not significant (Supporting information, Fig. S7b). The levels of mDC (Supporting information, Fig. S7c) and pDC (Supporting information, Fig. S7d) were similar in irradiated and

non-irradiated NSG–BLT mice. In addition, innate cell subsets developing in the NSG–BLT mice were comparable to the populations in human blood. Together, these results suggest that Neratinib ic50 irradiation conditioning of the recipient slightly enhances human macrophage development in NSG–BLT mice but is not necessary for mDC or pDC development. The standard implantation site for thymic and liver fragments in the BLT model is within the subcapsular space of the kidney. However, this procedure is considered survival surgery for the mice and is labour-intensive. As an alternative to the renal capsule, we tested whether implantation of thymic and liver fragments subcutaneously would support high levels of T cell development. NSG mice were irradiated with 200 cGy, implanted with 1 mm3 fragments of human fetal thymus and liver either in the renal subcapsular space or subcutaneously, and then injected i.v. with human HSC derived from the fetal liver. At 18 weeks post-implant the mice were evaluated for total human cell chimerism (CD45+ cells), for human T cell development (CD3+ cells) and for human B cell development (CD20+) in the blood and spleen (Fig. 4a–c). No significant differences were detected for the percentage of CD45+ cells in the blood and spleen (Fig.

These tumors are typically slow growing, with an indolent but progressive clinical course. We present a case of a highly proliferative chordoma arising in a 73-year-old woman with unusually rapid clinical growth and aggressive histologic and immunohistochemical features. This patient had an unusually brief preclinical course and within 1 month of developing headaches presented to medical attention with diplopia.

The resected chordoma showed uncommonly elevated mitotic activity, without the histologic hallmarks of de-differentiation. This proliferative activity correlated with elevated Ki67 staining (60%), B-cell leukemia/lymphoma1 (BCL1) expression Protein Tyrosine Kinase inhibitor (100%), and topoisomerase

IIα staining (>95%). E-cadherin expression was also lost throughout the majority of the tumor. Other markers of epithelial mesenchymal transition (EMT) including vimentin, N-cadherin, Slug and Twist, were also strongly expressed in this aggressive tumor. The sellar component of the tumor recurred within a 2-month interval. The evaluation of the additional biomarkers, including makers of EMT studied in this, case may allow for identification of aggressive chordomas in which the tempo of disease is significantly more rapid than in typical cases of chordoma. “
“Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous Adenosine triphosphate amoebic encephalitis. We report herein an autopsy case of B. mandrillaris Y-27632 amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren’s syndrome, manifested drowsiness 2 months before his death with progressive deterioration.

Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10–60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature. “
“C. Troakes, T. Hortobágyi, C. Vance, S. Al-Sarraj, B. Rogelj and C. E.