As illustrated in Fig. 4E, the addition of CXCR3+ CD25hi cells into the cultures in increasing ratios suppressed proliferative responses to baseline. Taken together, these observations indicate that subset(s) of CXCR3-expressing T cells have potent immunoregulatory properties. We next evaluated the functional implications

of CXCR3 BGJ398 clinical trial expression on Tregs for IP-10-dependent chemotaxis. Leukocyte migration was measured using a microfluidic technique that allows for precise and robust measurements of leukocyte migration at single-cell resolution 46. Purified CD4+CD25+ CD127dim/− Tregs were FACS-sorted into CXCR3pos or CXCR3neg subsets and were introduced into the main channel of the microfluidic device (Fig. 5A). Subsequently, images of live-time cell migration toward the chemokine IP-10 selleck kinase inhibitor were captured using time-lapse imaging, as described in Materials and methods. In the absence of a chemoattractant stimulus, we found minimal migration of T cells into the 6×6 μm side channels, and cells that entered the channels appeared to move at random.

However, as illustrated in Fig. 5B and C, we found that CXCR3+ Tregs had a marked chemotactic response toward IP-10, and their directional persistence was significantly greater (p<0.01) than that observed for CXCR3neg Tregs (Fig. 5D). CXCR3neg subsets were found to move in a random manner, some cells entered the channel and returned to baseline, and some migrated toward IP-10. In general, the directional persistence of CXCR3neg subsets was limited (Fig. 5D). We also observed that the velocity

of CXCR3pos cells during persistent directional migration was consistently slower than the velocity of random migrating CXCR3neg Tregs (but this difference did not reach statistical significance, data not shown). Collectively, these studies demonstrate that CXCR3 is functional to elicit chemotaxis in CXCR3-expressing Tregs. We next wished to evaluate the co-expression of CXCR3 with well-established lymphoid and peripheral homing receptors on FOXP3+ Tregs. We stained PBMC for CD4, CD25, FOXP3 and either CXCR3, CD62L, CCR4, CCR5 and CCR7, established to be expressed on Tregs 22–26. We also evaluated the co-expression of CXCR3 pheromone with Treg-associated homing receptors. Illustrated in Fig. 6A and B, we found comparable levels of CXCR3 and CD62L expression on both CD25hiFOXP3+ Tregs and CD25loFOXP3− Teff subsets. However, among chemokine receptors, we found lower levels of expression of CCR7 and higher levels of CCR4 and CCR5 on FOXP3+ Tregs versus Teff subsets. Also, we observed that CXCR3 is co-expressed with CD62L on ∼30% of FOXP3+ Tregs, while only ∼12% Tregs co-express CCR7 and CXCR3; and ∼20% CXCR3pos Tregs co-express CCR4 or CCR5 (Fig. 6B).

It has been reported that actin filaments associate with the Golgi network and contribute to the remodeling of this organelle during directed secretion 37. Furthermore, interfering with actin polymerization was shown to disrupt the Golgi and reduce directed secretion 38. We found that Golgin-97 codistributes with cytolytic granules in YTS cells (unpublished data). It will be

interesting to examine the effects of IQGAP1 deficiency on Golgi–actin interaction and establish whether the absence of perigranular actin in IQGAP1-deficient find more cells impacts on Golgi remodeling and functions. Such an effect could potentially contribute to the reduced cytolytic activity of IQGAP1-deficient NK cells. The functional roles of IQGAP1 in NK cells are unknown. However, the effects of IQGAP1 silencing on NK morphology and adhesion suggest that it may be important in limiting changes to cell shape and motility. Live cell analysis indicated that the silenced cells developed progressive extensions of micro projections that were normally short lived and smaller in wild-type cells. This appeared to be the basis for the resultant extended ABT-263 morphology of the silenced cells. The reduction of IQGAP1 also resulted in an increased

proportion of the cells forming conjugates with target cells. This could reflect an inability of these cells to release from non-productive interactions with the target cells. In each of these cases, the presence of IQGAP1 appeared Loperamide to correlate with the capacity to limit commitments to cytoskeletal changes associated with extension or adhesion. A recent study on murine NK cells suggested the formation of IQGAP1-mediated signalosomes upon NKG2D engagement, which facilitates Raf/MEK1/2/ERK1/2 signal transduction during cytokine and chemokine generation by these cells. The authors observe activation-dependent changes in the localization of IQGAP1 and in its colocalization with ERK1/2 24. Although we did not observe such redistribution

of IQGAP1 upon target cell engagement, the possibility of IQGAP1-mediating signal transduction possibly by associating with ERK1/2 in human NK cells is intriguing and warrants further study. The data presented here provide new information on the functional requirement for IQGAP1and on the distributional changes that occur during the formation and maturation of the NKIS. IQGAP1 is essential for MTOC mobilization and polarization. It also appears to play an important role in confining granule distribution in the cytosol of YTS cells, possibly through the organization of a filamentous actin network in the proximity of the granules. The similarities in the distribution patterns observed during synapse maturations suggest that IQGAP1 may play an analogous role in NK-like YTS cells, primary NK cells, and cytotoxic T cells. The human NK tumor cell-line YTS was maintained in RPMI 1640 (Gibco) supplemented with 15% fetal bovine serum (FBS).

Strikingly, the number of differentially expressed genes between pIgR KO and WT mice was reduced to 27 when the conventional microbiota was suppressed by antibiotic treatment (Fig. 1A, red circle, and Supporting Information Table 2). We also compared gene expression between antibiotic-gavaged

pIgR KO and pIgR KO with a conventional intestinal microbiota and found 296 genes that were more than twofold differentially expressed (Fig. 1A, AZD0530 concentration yellow circle, and Supporting Information Table 3). Notably, 74 of the 208 genes differentially regulated between pIgR KO and WT mice with conventional microbiota were also regulated by antibiotic treatment (Fig. 1A, overlap between yellow and blue, and Supporting Information Table 4). To verify

the microarray results, we performed quantitative RT-PCR on several of the most up- or downregulated genes found within this overlap (Fig. 1B). We also verified by RT-PCR that AZD2281 concentration the mRNA encoding the xenobiotic-modifying enzymes, sulfotransferase family 1D member 1 (Sult1d1), and aldo-keto reductase family 1member 19 (Akr1c19) were downregulated in untreated pIgR KO (Fig. 1B). Interestingly, several AMPs were among the most upregulated in conventional pIgR KO compared with conventional WT colonic EC. Furthermore, expression of these genes was downregulated when the conventional microbiota was suppressed by administration of broad-spectrum antibiotics by gavage. To validate the microbiota-dependent differential expression of AMPs in pIgR KO and WT mice, we performed RT-PCR studies of several α-defensins (Supporting Information Fig. 1). These results confirmed the findings revealed Clomifene by microarray analysis. We found that colonic epithelial gene expression was altered in pIgR KO mice compared with WT mice and

hypothesized that this could be due to altered composition of the commensal microbiota between the two genotypes. To address this question, we analyzed the intestinal microbial communities in pIgR KO and WT mice by 16S rRNA gene-targeted phylogenetic microarray analyses. Total DNA was extracted from mouse cecum and fecal pellets from both genotypes of mice carrying conventional microbiota and subjected to mouse intestinal tract chip (MITChip) microarrays. This method can identify approximately 2000 operational taxonomic units (OTUs) characterized from mouse intestinal microbiota, and has recently been used to profile murine gut microbiota in different studies [25-28]. We first compared the microbial diversity of cecal and fecal samples from pIgR KO and WT mice and found a greater diversity in the cecal community in WT animals (Fig. 2A). Multivariate redundancy analysis (RDA) revealed that intestinal locations (feces, cecum) impacted the gut microbiota composition more than genotype (Fig. 2B).

Domain I, the N-terminal ∼120 residues, is highly basic and is probably involved in the recruitment of the viral RNA during particle formation. Domain II, situated between a.a.∼120 and ∼175, has been predicted to form one or two alpha-helices that are presumed to be involved in the association of Core with membrane proteins and lipids. This domain is not present in the capsid proteins of most of the other members of the Flaviviridae family. It has recently been shown that the cysteine residue at a.a.128 is responsible for the disulfide-bonded dimer of Core and for particle formation (19). Domain III, located at

the C-terminal ∼20 residues, is highly hydrophobic and has been predicted to form an alpha helix. This domain serves as a signal sequence selleck compound Cilomilast solubility dmso for E1 as described above. The ubiquitin-proteasome pathway, a major route by which selective protein degradation occurs in eukaryotic cells, is involved

in post-translational modification of Core (20–25). Ubiquitin ligase E6AP has been identified as a core-binding protein that enhances its ubiquitylation and degradation. It has been suggested that E6AP-dependent degradation of Core is common to a variety of HCV isolates and plays a critical role in the HCV life cycle (23). Recently, we also demonstrated that proteasomal degradation of Core is mediated by two distinct mechanisms. One leads to polyubiquitylation in which lysine residues in the N-terminal region are preferential ubiquitylation sites. The other is ubiquitin-independent, from but depends on interaction with proteasome activator PA28gamma (24). Although is so far unclear as to whether destabilization of Core via two distinct mechanisms is physiologically significant, it is reasonable to consider that tight control over cellular levels of Core may contribute to restricting its potential for functional activity. E1 and E2 proteins are essential

components of the virion envelope and are necessary for viral entry. These glycosylated proteins extend from a.a. 192–383 (E1) and from a.a. 384–746 (E2) of the polyprotein, and have molecular weights of 33–35 and 70–72 kDa, respectively (26). Intracellular envelope proteins mainly exhibit high-mannose type glycans, consistent with their accumulation in the ER (27), whereas infectious-virion-associated envelope proteins display a mixture of high-mannose and complex types of glycans. It has been shown that E1 and E2 are heavily glycosylated, suggesting that HCV glycoproteins are processed by Golgi-resident glycosidases and glycosyltransferases (28). Complex N-linked glycans have also been detected on the surface of HCV particles isolated from patient sera (29). Based on prediction of membrane topology, it is hairpin structures that pass through the membrane twice, thereby allowing processing by a signal peptide in the ER lumen (30).

The restriction to the manipulation of the immunoglobulin gene locus allows the dissection of B-cell versus T-cell contribution to the acute allergic phenotype. This new mouse strain allows active immunization experiments to sensitize for anaphylaxis induction. We believe this is closer to the dynamic in vivo situation in allergic patients where polyclonal or oligoclonal antibody responses of different antibody isotypes are induced.

The results presented here suggest that a strong antigen-specific polyclonal IgE response is most powerful in sensitizing both Ivacaftor solubility dmso basophils and mast cells. Nevertheless, basophil-depletion experiments indicate that antigen-specific Tipifarnib price IgE on basophils plays an important role in the anaphylactic process in vivo. This view is indirectly supported by recent data that an IgE-specific hypersensitivity inhibiting molecule called Allergin-1, is expressed on

mast cells but not basophils [9]. Mast cells, however, do contribute to the anaphylactic reaction in vivo, since a partial anaphylactic drop in body temperature occurs even in basophil-depleted mice. Our data are in partial contrast to results, which suggested that basophil-dependent passive systemic anaphylaxis is IgG1 mediated, but not IgE mediated [9, 37]. The probable reason for this difference is that passive sensitization with monoclonal IgE is less efficient, due to the instability of IgE, compared with a polyclonal IgE antibody response. Recently, Parvulin Sawaguchi et al. showed that in a passive systemic anaphylaxis model, mast cell but not basophil depletion inhibited anaphylaxis [38]. In addition, Ohnmacht et al. [40] demonstrated for the Mcpt8Cre-basophil-deficient mouse model that

in active systemic anaphylaxis no difference between controls and the basophil-lacking mice exist. This does not contradict our data, because in the IgEwt/wt mice, where IgG1 levels dominate IgE, basophil depletion has only a minimal suppressive effect on anaphylaxis. This supports the hypothesis that basophils are dispensable for an IgG1-dominated anaphylaxis reaction [39]. Studies with novel basophil- or mast cell-deleted mouse strains have to be performed in order to elucidate the precise contribution of basophils versus mast cells in IgE-mediated active anaphylaxis [39, 40]. Further support for our model comes from experiments, which suggest that IgG-containing immune complexes inhibit (via FcgRIIB) rather than activate (via FcgRIIIA) basophils. They also show an inhibitory effect of IgG on IgE-mediated basophil activation, suggesting that the lack of an inhibitory signal by IgG1 could contribute to the increased IgE-mediated anaphylaxis we observed in IgEki/ki mice [18, 21]. First, we used CD23−/− to avoid passive binding of IgE to B cells.

One tumour was composed of cells with either an oligodendroglial or an astrocytic phenotype. Perivascular collections of

lymphocytes, eosinophilic granular bodies and Rosenthal fibres were also noted in this case, but the tumour contained neither piloid cells nor ganglion cells. A PLX-4720 supplier delicate branching vasculature of fine capillaries characterized many areas in all tumours, and hyalinized vessels were present in one case. High-grade features including mitotic activity, microvascular proliferation and necrosis were not identified. In all cases, many tumour cells demonstrated immunoreactivities for glial fibrillary acidic protein (GFAP) and S-100, but there was no immunoreactivity for synaptophysin. Neurofilament protein (NFP)-immunopositive axon twigs were variably present between tumour cells, but were generally sparse, indicative of the non-infiltrative nature of BIBW2992 nmr these tumours. Ki-67 immunolabelling was very low in all four cases. There was no immunoreactivity for the IDH1:p.R132H mutant gene product or for MYB. FISH detected no copy number alterations at the BRAF,

MYB or CDKN2A loci. One tumour harboured a BRAF:p.V600E mutation. While microscopic dystrophic calcification is commonly seen in diverse pathologies of the CNS, including LGGs, dense widespread macroscopic calcification is rare [7]. Reports of this phenomenon document its presence in association with several types of glioma: intraventricular pilocytic astrocytoma [1, 4],

diffuse astrocytomas of cerebellum [6], medial temporal lobe [3] and brain stem [5], and grade II ependymomas [2, 8]. Tumours in our series of massively calcified LGGs have architectural and cytological features that are not readily aligned with those of pilocytic astrocytomas, diffuse LGGs or uncommon astrocytomas, such as the pleomorphic xanthoastrocytoma. They tend to be circumscribed, without the infiltrative behaviour of diffuse LGGs, yet have a cytology that is not typical of a pilocytic astrocytoma. This idiosyncratic morphology also characterized three massively calcified astrocytomas from the International Society of Pediatric Oncology (SIOP) LGG1 tumour series [9], which was reviewed by one Tenofovir clinical trial of our authorship (D.W.E.). While other reported cases appear to be more readily interpreted as pilocytic [1, 4] or diffuse astrocytomas [3, 5, 6] or ependymomas [2, 8], we sought to address the difficulties with classification in our series utilizing molecular analysis. One tumour harboured a BRAF:p.V600E mutation, which is found in up to 23% of diffuse astrocytomas and 9% of pilocytic astrocytomas [10, 11], although it is more frequent in pleomorphic xanthoastrocytomas (65–75%) and gangliogliomas (15–25%) [10, 11]. Otherwise, no tumour demonstrated an IDH1:p.

The antibodies used in this work are listed

in Supporting Information Table 1. DNA primers were purchased from TIB-Molbiol (Berlin, Germany) and Life Technologies (Darmstadt, Germany) and listed in Supporting Information Tables 2 and 3. EL4 cells were cultured in DMEM medium. RLM11 and primary T cells were cultured in RPMI1640 medium. Both media were supplemented with 10% FCS. BMDMs were grown as described [107]. Human CD4+ cells were isolated using magnetic-activated cell sorting (MACS) technology (Miltenyi find more Biotec, Bergisch Gladbach, Germany) from blood of healthy volunteers (DRK, Berlin, Germany), collected according to the rules of the local ethics committees on human studies (Charité, Berlin, Germany). Mouse total CD4+ T and naive CD4+CD25−CD62L+ cells were isolated from spleen, mesenterial, popliteal, and auxiliary lymph nodes by MACS. CD4+ T cells from FoxP3-IRES-GFP mice were fractionated into FoxP3+ and FoxP3− cells by fluorescence-activated cell sorting (FACS) technology using FACSAria or FACSDiVa flow cytometers (BD Biosciences, Franklin Lakes, NJ, USA). Naive T cells were mixed with irradiated CD4− cells at the ratio of 1:5 and polarized under CHIR 99021 Th1, Th2, and Th17 conditions (summarized

in Supporting Information Table 4). Polarization efficiency was assessed by measurement of lineage-specific cytokines (Supporting Information Fig. 10). Restriction enzyme accessibility assay was performed as described [108]. All enzymes were from New England Biolabs (Ipswich, MA, USA). Briefly, cells were washed with ice-cold PBS, centrifuged for 5 min at 500 × g, resuspended in lysis buffer 1 Quisqualic acid (L1) (10 mM TrisHCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.5% Nonidet P-40, 0.15 mM spermine, and 0.5 mM spermidine) and incubated on ice for 5 min. Nuclei were centrifuged for 5 min at 500 × g, washed and resuspended in 50 μL of appropriate restriction enzyme buffer. A total of 30 U of restriction enzyme were added, and nuclei were incubated at 37°C for 15 min. The reaction was stopped

by adding 450 μL of DNA isolation buffer (100 mM NaCl, 10 mM TrisHCl, pH 8.0, 25 mM EDTA, 0.5% SDS), supplemented with 10 μL of 20 mg/mL Proteinase K (Biodeal, Markkleeberg, Germany) and incubated for 2 h at 56°C with shaking. Then, 300 μL of 3 M NaCl were added, samples were vortexed, and centrifuged for 15 min at 20 000 × g and 4°C. Supernatants were transferred to new tubes, supplemented with 10 μg of glycogen, and mixed with 750 μL of isopropanol. DNA was precipitated by 30 min centrifugation at 20 000 × g and 4°C, washed with 70% ethanol, dried, resuspended in 5 mM TrisHCl, pH 8.5, and analyzed by Southern blotting. Cells were fixed for 10 min with 1% formaldehyde in PBS at room temperature (RT). The fixation was stopped by adding glycine to the final concentration of 125 mM, cells were incubated for 5 min at RT, washed with cold PBS, resuspended in L1 buffer, and incubated for 10 min on ice.

The subjects were randomly assigned to either the control arm (supportive therapy alone) or the itraconazole arm (itraconazole 400 mg day−1 with supportive find more therapy). The randomisation sequence was computer generated using the statistical package StatsDirect for MS-Windows (Version 2.7.2, England, StatsDirect Ltd, 2005. http://www.statsdirect.com). The assignments were placed in sealed opaque envelopes and each patient’s assignment to a particular group was made sequentially. Blinding of treatment allocation was not possible. Itraconazole (Fungitrace, Lifecare Pharma, Gurgaon, India) was administered at a dose

of 200 mg twice a day along with meals (or orange juice) for 6 months. Drug levels of itraconazole were not performed. During the study period, no proton pump inhibitors or other acid reducing medicines were allowed. Adherence to itraconazole was assessed by instructing patient to bring the empty pill covers of the drug. Supportive therapy included antitussives (combination of dextromethorphan 10 mg, triprolidine 1.25 mg and phenylephrine 5 mg twice daily), iron and vitamin supplements (100 mg Ruxolitinib molecular weight of elemental iron as ferrous ascorbate; folic acid 1 mg day−1), and bronchial artery embolisation and/or surgery as and when indicated. All patients underwent the following investigations

at baseline: chest radiograph, CT of the chest, serum precipitins against Aspergillus species, flexible bronchoscopy, sputum/BALF culture for Aspergillus and mycobacteria, spirometry, complete blood count, liver function tests and electrocardiogram. Aspergillus skin test and total serum IgE levels were performed to exclude ABPA. At 6 months CT chest, spirometry and complete blood count were repeated. Liver function tests were performed every 1–2 months or immediately if patients complained of jaundice, easy fatiguability, loss of appetite or right upper quadrant abdominal pain. All data were recorded on a

standard questionnaire. Clinical response was classified as improved, stable or worsened based on assessment of patient’s sense of well-being, gain in weight, improvement in cough and exercise capacity, decrease in the number, and frequency Rho and quantity of haemoptysis. Radiological response was considered present if there was decrease in the size/number of the fungal balls, attenuation of the paracavitary infiltrates or pleural fibrosis. The response was assessed objectively by measuring the longest diameter of various lesions and a 50% reduction was taken as criteria for improvement. Overall response was classified as[2]: (a) improved: improved or stable clinical response and radiologically improved or stable disease; and (b) failed: worsening of symptoms or radiological progression. All outcomes were assessed at the end of 6 months of therapy. Patients were followed up for at least 6 months following completion of treatment.

In our case, the NFTs were seen in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei.

We could not know why both Orrell’s case and our case had NFTs, deviating from other FALS cases. In both cases, the distribution of NFTs was different from that in Alzheimer’s disease or other degenerative diseases. If we consider the fact that both cases had NFTs, mainly in the brain stem, the I113T mutation itself might be involved in the appearance of NFTs. As Orrell’s case and ours were so different in terms of disease duration, the timing of the appearance of NFTs would not seem to depend on the disease duration. In our present case Selleck Carfilzomib of the I113T mutation, we observed CIs and LBHIs, as well as NFTs. We examined these inclusions immunohistochemically in detail. However, clinicopathological studies including gene analysis and immunohistochemical selleck kinase inhibitor examinations of additional ALS cases are essential. The authors have no conflicts of interest to disclose. “
“Spontaneous intracerebral hemorrhage (ICH) is a devastating cause of morbidity and mortality. Intraparenchymal hematomas are often surgically evacuated. This generates fragments of perihematoma brain tissue that may elucidate their etiology.

The goal of this study is to analyze the value of these specimens in providing a possible etiology for spontaneous ICH as well as the utility of using immunohistochemical markers to identify amyloid angiopathy. Surgically resected hematomas from 20 individuals with spontaneous ICH were examined with light microscopy. Hemorrhage locations included 11 lobar and nine basal ganglia hemorrhages. Aβ immunohistochemistry and Congo red stains were used to confirm the presence of amyloid angiopathy, when this was suspected. Evidence of cerebral amyloid angiopathy (CAA) was observed in eight of the 20 specimens, each of which came from lobar locations. Immunohistochemistry confirmed CAA in the brain fragments from these eight individuals. Patients with

immunohistochemically confirmed CAA were older than patients without CAA, and more likely to have lobar hemorrhages (OR 3.0 and filipin 3.7, respectively). Evidence of CAA was not found in any of the basal ganglia specimens. One specimen showed evidence of CAA-associated angiitis, with formation of a microaneurysm in an inflamed segment of a CAA-affected arteriole, surrounded by acute hemorrhage. In another specimen, Aβ immunohistochemistry showed the presence of senile plaques suggesting concomitant Alzheimer’s disease (AD) changes. Surgically evacuated hematomas from patients with spontaneous ICH should be carefully examined, paying special attention to any fragments of included brain parenchyma. These fragments can provide evidence of the etiology of the hemorrhage. Markers such as Aβ 1–40 can help to identify underlying CAA, and should be utilized when microangiopathy is suspected.

Since there is a lack of data, we aimed to define the expression pattern and cellular source of TNFRSF9 in human gliomas. C59 wnt in vivo We investigated TNFRSF9 expression in normal human CNS tissue and glioma

specimens using immunohistochemistry, immunofluorescence and western blotting techniques. Our results show that TNFRSF9 is considerably upregulated in human gliomas when compared to normal brain tissue. In addition, our data provides evidence for an immune cell-independent de novo expression pattern of TNFRSF9 in mainly non-neoplastic reactive astrocytes and excludes classic immunological cell types, namely lymphocytes and microglia as the source of TNFRSF9. Moreover, TNFRSF9 is predominantly expressed in a perivascular and peri-tumoral distribution with significantly higher expression in IDH1 mutant gliomas. Our findings provide a novel, TNFRSF9-positive, reactive astrocytic phenotype and challenge the therapeutic suitability of TNFRSF9 as a promising target for human gliomas. “
“Uranium olfactory uptake after intranasal exposure raises some concerns for people potentially exposed to airborne radionuclide contamination as the brain could be a direct target for these contaminants. A model of nasal instillation was used to elucidate the transport

mechanisms of uranium to the brain and to map its localization. Increasing concentrations of depleted uranium containing solutions were instilled in the nasal cavity of adult male rats. Uranium concentrations https://www.selleckchem.com/products/chir-99021-ct99021-hcl.html were measured using inductively coupled plasma-mass spectrometry (ICP-MS) 4 h after instillation. Olfactory neuroepithelium cytoarchitecture was

studied using immunohistochemistry experiments. Secondary ion mass spectrometry (SIMS) microscopy Phosphatidylinositol diacylglycerol-lyase was performed to localize uranium in the olfactory system. ICP-MS analyses showed a frontal accumulation of uranium in the olfactory bulbs associated with a smaller increase in more caudal brain regions (frontal cortex, hippocampus and cerebellum). Uranium concentrations in the olfactory bulbs do not reach a saturation point. Olfactory nerve bundle integrity is not affected by uranium as revealed by immunohistochemistry. SIMS microscopy allowed us to show that uranium localization is mainly restricted to the olfactory neuroepithelium and around olfactory nerve bundles. It is subsequently detected in the olfactory nerve layer of the olfactory bulb. These results suggest the existence of a transcellular passage from the mucosa to the perineural space around axon bundles. Uranium bypasses the blood brain barrier and is conveyed to the brain via the cerebrospinal fluid along the olfactory nerve. Future studies might need to integrate this new contamination route to assess uranium neurotoxicity after nasal exposure. “
“We present a rare case of primary T-cell lymphoblastic lymphoma of the pituitary gland. A 58-year-old woman presented with headaches, right-sided ptosis and cranial nerve III palsy.