In conclusion, these findings reinforce the role of IFI16 as a mediator of the immunomodulatory and proinflammatory activities of IFN that regulate the early defence mechanisms against infections. HUVEC cultured in endothelial growth medium (EGM-2, Lonza, Milan) containing 2% fetal bovine serum, human recombinant vascular endothelial growth factor, basic fibroblast growth factor, human epidermal growth factor, IGF-1, hydrocortisone, ascorbic acid, heparin, gentamycin and amphotericin B (1 μg/mL each) were seeded into 60 mm culture dishes coated with 0.2% gelatin. Experiments were performed with cells between passages 2 and 6. Human

embryo kidney 293 cells (Microbix Biosystems) were cultured in minimum Lapatinib order Eagle’s medium (Invitrogen) supplemented with 10% fetal bovine serum (Sigma, Milan, Italy), 2 mM glutamine, 100 units of penicillin per milliliter and 100 μg/mL of streptomycin

sulfate. Adenovirus-derived vectors expressing either IFI16 or LacZ were generated as described previously 9. Briefly, the www.selleckchem.com/products/Gefitinib.html pAC-CMV IFI16 containing the human IFI16 cDNA linked to a FLAG tag at the N-terminus was cotransfected together with pJM17 into human embryonic kidney 293 cells. After several rounds of plaque purification, the AdVIFI16 was amplified on 293 cell monolayers and purified from cell lysates by banding twice on CsCl gradients. Recombinant AdVIFI16 Urease was tested for IFI16 expression by Western blotting using an anti-FLAG Ab (Sigma). For cell transduction, preconfluent HUVEC were washed once with PBS and incubated with either AdVIFI16 or AdVLacZ (used as a control) at a MOI of 300 in EGM-2. After 60 min at 37°C, the virus was washed off

and fresh medium added. Cells were cultured for 36 h before use in the experiments. RT-PCR analysis was performed on an Mx 3000 PTM (Stratagene) using the SYBR Green I dye (Fermentas) as a nonspecific PCR product fluorescence label. Total cellular RNA was isolated using the Nucleospin Extract RNA II (Macherey Nagel). RNA (1 μg) was then retrotranscribed at 42°C for 60 min in PCR buffer (1.5 mM MgCl2) containing 5 μM random primers, 0.5 mM dNTP and 100 units of RevertAid H Minus M-MuLV Reverse Transcriptase in a final volume of 20 μL. cDNA (1 μL), or water as control, were amplified in duplicate by RT-PCR using the Brilliant SYBR Green QPCR master mix (Fermentas) in a final volume of 25 μL. Primer sequences are summarized in Table 2. The Ct values for each gene were normalized to the Ct values for β-actin using the Ct equation. The level of target RNA, normalized to the endogenous reference and relative to the mock infected and untreated cells, was calculated by the comparative Ct method using the 2−δδCt equation. For transfection experiments, HUVEC grown to subconfluence were detached and transfected with 0.

Recent progress in understanding the interaction between immune/inflammatory cell subsets via interleukins, particularly reciprocal regulation and counter balance between Th1, Th2, Th9, Th17, Th22 and T regulatory cells, as well as B-cell subsets, bring new possibilities for immune intervention. With regard to allergic diseases, the process of developing LEE011 molecular weight such diseases is characterized by effector Th2 cells that produce IL-4, IL-5, IL-9 and IL-13 1–4. In addition, recently defined cytokines, such as IL-25, IL-31, IL-32 and IL-33 that contribute to Th2

responses, tissue inflammation, allergen-specific IgE production, eosinophilia, mucous production, and the activation and cell death of the epithelium represent newly emerging and essential players in the pathgogenesis of allergic inflammatory disease 5–9. In the context of tissue-related allergy-driving factors, the IL-1 family member cytokine IL-33 is becoming a key player in the initiation and exacerbation of inflammatory responses. Its effects are exerted via its heterodimeric receptor that consists of ST2 and the ubiquitously expressed IL-1 receptor accessory protein (ILRAcP) buy Talazoparib 10. IL-33 integrates both innate and adaptive immunity in a unique manner. It affects basophils, mast cells, eosinophils, innate lymphoid cells, NK and NKT cells and Th2 lymphocytes 2, 11. In addition, IL-33 impacts CD34pos precursor cell populations 12 and is involved

in the activation of a cell subpopulation called nuocytes that are crucial for triclocarban parasite repulsion. This nuocyte population was defined as lineageneg ICOSpos ST2pos IL-17RBpos and IL17Rapos

cells and is considered to be an upstream Th2 inducer/amplifier, whose properties still remain to be defined in detail 7. The actions of IL-33 seem to be particularly evident when looking at models of mucosal inflammation. In this issue of the European Journal of Immunology, an article by Besnard et al. adds significant information regarding the role of IL-33 in the context of a mouse model of asthma-like lung inflammation 13. The authors demonstrate that IL-33 acts, in an ST2-dependent manner, as a maturation factor for BM-derived DCs via up-regulation of CD80, CD40 and OX40L. This process is accompanied by the release of pro-inflammatory cytokines, such as IL-6, IL-1β, TNF-α and TARC/CCL17. IL-33-pre-treated DCs were significantly more potent than non-treated DCs at inducing allergen-specific proliferation in naïve T-cells, and the generated T-cell responses were of a Th2 type with IL-5 and IL-13 production. This activation/maturation of lung resident DCs was also confirmed in vivo via local application of IL-33, inducing up-regulation of the homing receptor CCR7 in the CD11cpos fraction. The activated DC phenotype was observed in the draining LN, and PBMCs from the LN displayed a Th2 phenotype upon re-stimulation with anti-CD3/CD28.

2C, top). The same results were obtained when viral titers in IgMi mice after

LCMV Docile infection were analyzed (Fig. 2C, bottom). Taken together, these data suggested that Abs induced in the early phase of an LCMV Docile Abiraterone price infection were required to prevent T-cell exhaustion and viral persistence. Due to the phenotype of Ab-deficient mice after LCMV Docile infection, we used this viral strain for all subsequent experiments of this study. Next, we determined the kinetics of the LCMV-specific Ab response in B6 mice using a newly established sensitive sandwich ELISA as detailed in the Material and methods. LCMV-specific IgG titers in serum of LCMV Docile infected mice strongly increased between days 6 and 8 and reached maximal levels 2 weeks p.i. (Fig. 3A, filled circles). The IgG response was T-cell help dependent since Ab titers were strongly decreased in CD4+ T-cell-depleted mice (Fig. 3A, open circles). The viral antigen specificity of immune serum taken from LCMV Docile infected mice at d20 p.i. was analyzed by immunoprecipitation and immunoblotting. The results revealed that LCMV immune serum predominantly

contained Abs specific for LCMV NP (Fig. 3B) confirming previous data [14]. Importantly, virus neutralizing activity was never observed in these LCMV immune sera even when used at a high concentration (Fig. 3C). To provide additional evidence for the lack of virus neutralizing activity, virus serum mixes (90% GSK3235025 mw serum) were incubated overnight before inoculation into mice. Two days after inoculation,

LCMV titers in spleens were enumerated. The neutralizing LCMV GP specific mAb KL25 was used as a positive control in these assays. As shown in Fig. 3D, treatment with mAb KL25 completed prevented infection whereas preincubation with LCMV immune serum did not affect initial viral replication. Having shown that mice with impaired humoral immunity were unable to control LCMV Docile infection, we next wondered whether transfer of LCMV immune serum could accelerate virus clearance. First, LCMV Docile infected MD4 and IgMi mice were treated Farnesyltransferase with LCMV immune sera free of infectious virus that were obtained from infected wild-type mice at day 20 p.i. Viral titers in spleen, liver, and lungs were determined 14 days later. This treatment was able to lower viral titers in some mice but the antiviral effects were variable, particularly when using MD4 mice (Fig. 4). To obtain a more robust read-out for the potential antiviral activity of LCMV-specific Abs, we next tested B6 wild-type mice as hosts. Mice were infected with LCMV Docile and at day 1 serum from healthy uninfected mice (= normal serum) or LCMV immune serum was injected i.p. and the kinetics of viral elimination was followed. At day 2 and day 4 p.i., viral load between the two groups did not significantly differ (Fig. 5).

In their investigation of 19 patients, 15 had a total endoscopic approach, three had thoracotomy, and one had a video-assisted Forskolin research buy approach, which demonstrates that in some cases because of intraoperative complications thoracotomy might be necessary; however, most patients can profit from the smaller extent of the thoracoscopy. The benefit of lung resection for patients with pulmonary aspergillosis and underlying haematological malignancy was investigated by Matt et al. [78] in 41

cases. They found that a perioperative mortality of 10% which might seem promising. Authors concluded that surgery might be an option; however, the most important factor in long-term survival remains the management of the underlying haematologic disease. In 43 paediatric patients with IPA, Gow et al. [83] found that surgical resection of the involved lung parenchyma was significantly prognostic for survival (P < 0.001). As surgery is not a relevant option in those patients with underlying haematological malignancies under the highest risk for developing fatal IPA (while undergoing allogeneic haematopoietic stem cell transplantations or induction therapies for acute

leukaemia) selection bias in those studies might be an issue. Resection of a singular pulmonary lesion in case of planned high-dose chemotherapy or transplantation may be an option to prevent reactivation after high-dose chemotherapy or stem cell/solid NADPH-cytochrome-c2 reductase organ transplantation as reactivation selleck chemicals may occur in up to 30% in absence of surgery.[83-85] Studies evaluating this issue, however, are mostly 10 or more years old. Surgery also is a key factor in the management of Aspergillus pleural empyema. Pleural empyema mostly develops continuously from IPA by direct expansion or from a broncho-pleural fistula. Bonatti et al. [86] reported of four patients with pleural empyema after lung resection for various reasons. All four patients received surgical treatment, which consisted of partial pneumectomy, implantation of thoracostoma, secondary closure of the leaking

bronchial stump and subsequent closure of the thoracic gap, with pectoral or omental flaps in addition to systemic antifungal therapy. In this report, Aspergillus infection had to be cleared in the pleural cavity in order to be able to perform successful closure of the thoracic gap. In case of bronchopleural-cutaneous fistula, successful treatment of pleural empyema with antifungal treatment administered through a tube that is placed through the fistula, has been reported without further surgical intervention.[87] A large study, including 67 cases of fungal pleural empyema by Ko et al. [88], reported that all patients receiving surgery or pleural irrigation with antifungal agents survived. Surgery included also pleural decortication, which was performed in six patients (9%).

[9] The genus Lichtheimia contains four species, of which L. corymbifera and L. ramosa have been reported from human infections.[10] Reviews describing the less common members of Mucorales causing the remaining 20–30% of mucormycosis cases mostly include Actinomucor, Apophysomyces, Cokeromyces, Cunninghamella, Rhizomucor, Saksenaea and Syncephalastrum.[3, 11] The prognosis of invasive mucormycosis remains poor, with recently reported mortality selleck kinase inhibitor rates varying between 45% and 64%, and in some report 85%,[12] depending on the underlying disease.[13, 14] Early recognition of the source of infection is among the key elements in successful management of infection.[15] Conventional

diagnosis is difficult because symptoms, signs, radiographic manifestations and histopathology of mucormycosis are non-specific,[6] and culture of sputum, paranasal sinus secretions or bronchoalveolar lavage fluid is frequently unsuccessful. In general conventional diagnostics are slow, unsuited for screening purposes and may have limited specificity. Y27632 Mucoralean fungi are particularly suitable for molecular techniques because interspecific distances tend to be large and intraspecific variability is relatively low.[11] The most common molecular method in clinics so far is sequencing of the ITS and D1/D2 ribosomal

DNA (rDNA) regions and Blast comparison in available databases. Rolling circle amplification (RCA) is an isothermal amplification method which has been proved to be rapid, cost-effective and specific for molecular identification of pathogenic fungi.[16-18] In this paper, we propose seven padlock probes on the basis of the rDNA ITS region to identify the most clinical relevant taxa of Mucorales, viz. R. microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, M. irregularis (formerly Rhizomucor variabilis), M. circinelloides, L. ramosa and L. corymbifera. In total 42 strains from reference

collection of the Centraalbureau voor Schimmelcultures (CBS-KNAW Fungal Biodiversity Centre, Utrecht, the Netherlands), were used in this study and are listed in Table 1. Cyclic nucleotide phosphodiesterase The set included six strains each of R. microsporus, R. arrhizus var. arrhizus, R. arrhizus var. delemar, M. irregularis, M. circinelloides, L. ramosa and L. corymbifera, including strains tested as negative controls. Isolates were identified with different genetic markers prior this study and there is no conflict about their taxonomic identification.[8, 11, 19] Lyophilised strains were grown on 5% Malt Extract Agar (MEA; Oxoid, Basingstoke, UK) in 8 cm culture plates incubated at 30 °C for 3 days. DNA was extracted using a CTAB method as described previously.[19] ITS amplicons were generated with primers V9G and LS266. The ITS amplicons were used as targets for RCA reactions. ITS sequences of all strains were aligned and adjusted manually using BioNumerics v. 4.

Apoptosis of helper/inducer T-cells were observed in these active inflammatory lesions. Horizontal distribution of inflammatory

lesions was symmetric at all spinal levels and was accentuated at sites with slow blood flow in the middle to lower thoracic levels. HTLV-1 proviral DNA amounts were well correlated with the numbers of infiltrated CD4+ cells. find more In situ PCR of HTLV-1 proviral DNA and in situ hybridization of HTLV-1 Tax gene demonstrated the presence of HTLV-1-infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that T-cell mediated chronic inflammatory processes targeting the HTLV-1 infected T-cells is the primary pathogenic mechanism of HAM/TSP. Anatomically determined hemodynamic conditions may contribute to the localization of infected T-cells and the formation of main lesions in the middle to lower thoracic spinal cord. Human T lymphotropic https://www.selleckchem.com/HDAC.html virus type 1 (HTLV-1) is the first recognized human retrovirus and is found to be a causative agent of adult T-cell leukemia/lymphoma (ATL).1

Epidemiological survey of ATL and HTLV-1 seropositive carriers demonstrated the deviated distribution to southwestern Japan. In 1985, Osame and colleges noticed in one of the most endemic areas of HTLV-1, Kagoshima, that some patients manifesting slowly progressive spastic paraparesis with sphincter dysfunction had antibodies against HTLV-1 in both their sera and CSF. Further analysis of anti-HTLV-1 antibodies on stored

CSF specimens from various neurological diseases found additional cases with slowly progressive spastic paraparesis having anti-HTLV-1 antibodies. Their hematological features did not satisfy diagnostic criteria of ATL. Based on these finding, the term HTLV-1-associated myelopathy (HAM) was proposed as a new clinical entity.2 Independently, Gessain et al. have reported that about 60% of Caribbean patients with tropical spastic paraparesis (TSP) were seropositive for HTLV-1.3 during HAM and HTLV-1-positive TSP were later confirmed as a single clinical entity and the name HAM/TSP was recommended by WHO. HAM/TSP is characterized by a spastic paraparesis with urinary disturbances and anti-HTLV-1 antibody positivity in serum and CSF. Almost all patients show spasticity and/or hyper-reflexia of the lower extremities. Many patients manifest weakness of the lower extremities and a poorly defined (mild) sensory effect. These symptoms are generally slowly progressive, or in some cases static after initial progression, while patients at older ages of onset show faster progression regardless of the mode of transmission. Patients with HAM/TSP have high antibody titers to HTLV-1 both in serum and CSF. Aside from HTLV-1 antibody positivity, other essential laboratory findings include lymphocytic pleocytosis in the CSF and increased CSF neopterin levels. In MRI, high signals on T2-weighted images are observed in the white matter of the brain similar to those found in multiple sclerosis.

Moreover, lupus-prone MRLlpr mice, a model of human systemic lupus erythematosus, lacking TLR9 genes exhibited accelerated onset of lupus symptoms and more severe pathology compared with MRLlpr mice with intact TLR9 genes [29]. These observations emphasize the critical importance of evaluating immune responses to DNA rigorously in physiologic settings relevant to disease progression or therapy, since extrapolations based on responses to DNA by cultured cells may reflect cell-type specific responses to DNA but may nevertheless be misleading with regard to dominant

Cisplatin cost responses to DNA that manifest in vivo. DNA nanoparticles (DNPs), which contain the cationic polymer polyethylenimine and plasmid DNA (pDNA), are used as vehicles to transfer genes into cells and animals. DNPs are made by combining

polymers and cargo DNA to form nanoparticles with specific surface electrostatic charge and size ranges, which may have profound effects on DNP processing in physiologic tissues. DNPs have been shown to provoke proinflammatory cytokine production and anti-tumor immunity in mouse models of lung and ovarian cancer [30, 31]. Unexpectedly, systemic (intravenous) treatment of mice with DNPs was shown to induce IDO enzyme activity in tissues, but sensing of cargo plasmid DNA to induce IFN-αβ and IDO was not TLR9-dependent [32]. Moreover, IFN-αβ (but not IFN-γ) EPZ 6438 signaling was shown to induce IDO-dependent regulatory responses, which activated Treg cells to suppress helper/effector T-cell responses. In

a different study, regulatory responses to DNPs were shown to be STING-dependent and systemic cdiGMP treatment to activate STING directly induced IDO [33]. These Celecoxib findings revealed that DNP cargo DNA enters the cytosolic compartment of cells to trigger potent regulatory responses via the STING/IFN-β/IDO pathway, and that this immunogenic response is capable of overcoming the immunogenic responses coinduced by DNPs. Systemic DNP or CDN administration is a key factor driving dominant immune regulatory outcomes, as intramuscular and subcutaneous cdiGMP injection in mice was shown to enhance humoral and cell-mediated immunity to vaccination [34]. However, it is unclear why systemic DNP treatments suppress Th1 responses to immunizing antigens [32, 33] but induce anti-tumor immunity in tumor-bearing mice [31]; distinct local responses to DNPs in lymphoid tissues and tumor microenvironments may offer a potential explanation. The type of cell that senses cytosolic DNA is likely to be a key factor influencing downstream immunological outcomes.

Endogenous Atg5 and Atg12 are mainly

present as the Atg12-Atg5 conjugate, this conjugate being essential for autophagy. Therefore, when Atg5 and Atg12 are analyzed using an expression plasmid(s), negative controls should be used. The Lys130 within human Atg5 is essential for Atg12 conjugation (Fig. 2, Wild-type Atg12 and Atg5). An Atg5K130R mutant, in which essential Lys130 has been changed to Arg, has a defect in conjugate formation resulting in a defect of autophagosome formation (Fig. 2, Atg5K130R) (47). Therefore, mutant Atg5K130R is suitable as a negative control for Atg5. The carboxy-terminal Gly within Atg12 is also essential for formation of the Atg12-Atg5 conjugate. selleck compound A mutant Atg12ΔG lacking the carboxy-terminal Gly within Atg12 has defects in E1-like and E2-like reactions with

Atg7 and Atg3, respectively (Fig. 2, Atg12ΔG) (58, 51). Therefore, mutant Atg12ΔG is also suitable as a negative control for Atg5. It is necessary to use these negative controls to clarify whether the functional interaction between Atg5 (or Atg12) and a target protein is related to the conjugate, that is, to autophagy. The mRFP-GFP-tandem fluorescent protein-LC3-color change assay is based on a difference between GFP and mRFP in pH stability (89, 90). Autophagosomes have a pH similar to that of the cytosol, while autolysosomes have an acidic pH. At an acidic pH, the fluorescence of mRFP is stable, while that of GFP decreases. Therefore, the merged color of mRFP-GFP-LC3 in autophagosomes is yellow, while that in autolysosomes is red (89). This assay is suitable for real-time (and short-term) monitoring of autophagy, but care CDK activity should be taken when using it in long-term monitoring of this process. Fluorescence derived from GFP in the lysosomes has been observed even after degradation of LC3 (87). The amount of LC3- II increases during autophagosome formation, an initial step in autophagy, while LC3-II decreases during autophagosome-lysosome fusion and degradation of intra-autophagosomal contents by lysosomal hydrolases. Therefore, it is difficult to judge whether a transient assessment of LC3-II by immunoblotting represents activation

or impairment of autophagy. To resolve this issue, the LC3-II turnover oxyclozanide assay, a measure of autophagic flux in which LC3-II is assayed by immunoblotting with anti-LC3 antibody in the presence and absence of lysosomal inhibitors, is employed (76). A mixture of E64d (a membrane-permeable inhibitor of cathepsins B, H, and L) and pepstatin A (a membrane-permeable inhibitor of cathepsins D and E) is used to inhibit lysosomal function (91). Treatment of cells with this inhibitor cocktail results in significant accumulation of autolysosomes (and LC3-II dots) because there is little degradation of their contents. Thus, the accumulation of LC3-II reflects the activity of the process of delivering LC3-II into lysosomes, that is, autophagic flux.

7f). These findings were compatible

with a role of syk and lyn kinases in TLR-dependent signalling, making discrimination of TLR-dependent click here and BCR-dependent signalling nearly impossible. RAG re-expression in mature B cells has been described in a variety of studies.[7, 28-31] Importantly, and in marked contrast to the heavy chain locus, repeated rearrangements are possible at the LC loci. It is therefore not surprising that re-expression of RAG is associated with secondary LC rearrangements.[32, 33] In our study, high mRNA expression levels of polμ in human peripheral blood B cells (Fig. 3) and flow cytometric evidence for Igκ/Igλ rearrangement (Fig. 5) support this concept. Earlier studies in patient cells correlated CX5461 re-expression of RAG with CD5 expression and autocrine IL-6 levels.[3, 5, 6, 34, 35] In line with these observations, we previously showed that CpGPTO up-regulate CD5 expression,[17] but we could not confirm a direct association of CD5 and RAG expression (data not shown). Nevertheless, under in vivo circumstances CD5 expression probably reflects strong activation of RAG+ B cells as achieved by stimulation with CpGPTO in vitro.[17] This notion is supported by the finding that a stronger degree of B-cell activation – as it results from combined

stimulation with CpGPTO + CD40L ± rhIL-4 – concomitantly increases IL-6 production (Fig. 1a), proliferation (Fig. 1b) and associated expression of RAG-1 (Fig. 2b) and nuclear translocation of Ku70

(Fig. 4a). Nevertheless, re-induction of RAG expression in the periphery is a controversial issue.[36, 37] It should, however, be noted that Sandel and why Monroe[36, 37] proposed that B-cell escape from deletion and induction of RAG expression rely on a pro-survival signal inherent to the bone marrow environment. They further demonstrated that prevention of apoptosis can restore expression of RAG in immature transitional B cells. It can, therefore, not be excluded that a strong survival signal as induced by CpGPTO could enable re-expression of RAG and consecutive receptor revision. Since RAG-1 and RAG-2 are thought to act as a heterodimer,[38] our data indicate that RAG proteins and associated NHEJ enzymes display functional integrity in a small population of CpGPTO-treated B cells (Figs 2-5). However, despite flow cytometric evidence for Igκ/Igλ rearrangement (Fig. 5b) and detection of RAG-1 (Fig. 2), RAG-2 remained below the detection threshold. Differences in expression levels of RAG-1 and RAG-2 may be explained by a cluster of transcription initiation sites in the RAG-1 promoter that lowers the threshold for transcription.[39] Furthermore, RAG-1 serves as an E3 ubiquitin ligase that adversely regulates RAG-2 expression,[40] a property that may further accentuate differences in expression levels.

1%) and sensitivity (88.5%), in both Parkinson’s disease and dementia with Lewy bodies, suggesting that this finding can be a useful hallmark of Lewy body-related disorders. “
“Pseudopolyneuritic form of ALS is a subtype of ALS characterized by distal weakness of the unilateral lower limb and absence of Achilles tendon reflex (ATR) at disease onset. Recognition of this form of ALS is important for clinicians because the combination of distal weakness of the lower limb and absence of ATR usually suggests peripheral neuropathy. We reviewed the clinical records of 42 autopsy-proven sporadic ALS cases

and found three cases that showed onset of weakness of the unilateral lower limb with distal dominance and absence of ATR. The disease duration in the three cases was 2, 3 and 19 years, respectively.

The clinical features of the patient with a course of 19 years had been restricted to lower motor neuron signs. Histopathologically, consistent findings Selleck Ulixertinib in the three cases were severe motor neuron loss throughout the whole spinal cord, with relative preservation of the hypoglossal nucleus. Reflecting this finding, TDP-43-positive neuronal cytoplasmic inclusions in the spinal cord were sparse in two cases, and absent in a third. In the patient showing a clinical course of 19 years, mild corticospinal tract degeneration appeared to correspond to the absence of upper motor neuron signs and prolonged disease duration. In this case only, Bunina bodies were not demonstrated. In Sirolimus molecular weight this study, we clarified the clinical and pathological heterogeneity of this form of ALS. “
“Prader-Willi syndrome (PWS) is caused by

the absence of paternally contributed genes in chromosome 15, and is characterized by hypotonia, feeding difficulty, mental retardation, growth failure, hypogonadism and severe obesity. To elucidate the pathogenesis of neurological disorders, we immunohistochemically examined the PRKACG γ-aminobutyric acid (GABA)ergic interneurons (GABAis) in the cerebral cortex and acetylcholine neurons (AchNs) in the nucleus basalis of Meynert (MyN) and pedunculopontine tegmental nucleus pars compacta (PPNc) in an autopsy case of one PWS patient with a deletion in the 15q11-q12 region and three control patients. The GABAis in the cerebral cortex and AchNs in the MyN were well preserved in the PWS patient. The AchNs in the PPNc in the PWS patient were severely reduced in comparison with those in controls, whereas catecholaminergic neurons and GABAis were preserved. The selective loss of AchNs in the PPNc may be involved in hypotonia and/or REM sleep abnormalities in PWS patients. “
“Extraventricular neurocytoma (EVN) shares histological features with central neurocytoma, but has a wide morphological spectrum. Little is known regarding its clinicopathologic nature, biological behavior and genetic abnormalities. The aim of this study is to examine the diagnostic criteria, genetic abnormalities and biological behavior of EVN.