Results: The average thiamine level was 50.1 ng/mL (normal range, 24–66 ng/mL). Of the 100 patients included in the analysis, 15 were found to have reduced serum thiamine levels (<24 ng/mL). The patients were dichotomized according to the median serum thiamine level into a high-thiamine group (≥35.5 ng/mL) and a low-thiamine group (<35.4 ng/mL), and the clinical characteristics were compared between the two groups. The former group exhibited higher serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and exhibited Seliciclib lower C-reactive protein (CRP) than the latter group. We found a significant correlation

between the serum thiamin levels and the serum levels of AST and ALT (p < 0.0001, r = 0.44, p = 0.0002, r = 0.63). In addition, 18 patients showed a decrease from the baseline of the serum thiamine level post

hemodialysis. We divided these 18 patients into two groups, namely, the decrease group (n = 18) and the increase group (n = 82), and compared the clinical characteristics between the two groups. The comparison, however, revealed no significant difference in the Kt/V or type of dialyzer between the two groups. Conclusion: We conclude that thiamine deficiency did not occur in our regular dialysis patients, with the exception find more of a few cases. The serum AST or ALT may be used as a marker of thiamine deficiency in dialysis patients. TONGPAE Mephenoxalone PINCHART1, NONGNUCH ARKOM2 1M.D., Fellow Nephrology Division, Medicine Department,

Ramathibodi Hospital; 2M.D. Nephrology Division, Medicine Department, Ramathibodi Hospital Introduction: There are many techniques used in vascular access surveillance for hemodialysis with the goal to detect access stenosis before thrombosis occurs. The ideal technique is that easy to perform, cost-effective, widely available and highly accurate. The purpose of this study is to determine sensitivity and specificity of three diagnostic tests including Venous Static Pressure (VP), Ultrasound Dilution Test (UDT), Duplex Doppler Ultrasound (DDU) or combination tests. Method: Patients with chronic stable hemodialysis via permanent vascular access were recruited and measured static venous pressure, intra-access flow using UDT and DDU. All patients were confirmed by angiography which is the gold standard for diagnosis access stenosis. Each test was performed within two weeks apart. Results: All three tests were evaluated using Receiver Operating Characteristic curve and found that UDT had the AUC of 0.76 (95% CI 0.6 to 0.9), DDU 0.66 (95% CI 0.5 to 0.8) and VP 0.54 (95% CI 0.3 to 0.7). The cutoff value used to predict access stenosis was 750 ml/min for UDT, PSV 290 cm/sec for DDU, and ratio 0.2 for VP. When compared the results of combined VP and DDU to UDT using the same cutoff value as above, the sensitivity and specificity were similar.

In contrast, when transduced with mouse CD1d presentation of αGalCer and C20:2 was not affected ubiquitin-Proteasome system but the two NPC1 lines with the greatest lysosomal storage as defined by LysoTracker green staining (Fig. 3D) exhibited a significant defect in Gal(α1-2)GalCer presentation (Fig. 3C) compared with the other NPC1 EBV-B-cell line. Our study demonstrates that lysosomal

dysfunction does not alter iNKT-cell frequencies in the blood of NPC1 patients, implying that this compartment is not required for the generation or loading of iNKT-cell selecting ligand(s) in the human thymus. This is consistent with studies using in vitro models of human CD1d auto-antigen presentation [9], suggesting that loading occurs in the early endosomes. This is in contrast to the murine model of NPC1 in which peripheral iNKT cells are virtually undetectable, most likely because of impaired selection BMN673 in the thymus [6, 7]. Antigen presentation by human B-cell lines generated from NPC1 patients and heterozygotes and transfected with human CD1d demonstrated normal presentation of three different exogenous antigens, particularly Gal(α1-2)GalCer [9], which

needs the terminal sugar to be cleaved before it is recognised by iNKT cells [15], indicating that unimpaired lysosomal trafficking and/or function is not essential for human CD1d ligand loading. In contrast, and in agreement with the reported requirement for normal lysosomal trafficking/function for murine CD1d ligand loading, the two NPC1 B-cell lines that exhibited the greatest

lysosomal storage Tobramycin had reduced capacity to stimulate iNKT cells when pulsed with Gal(α1-2)GalCer. The differences between the murine model of NPC1 and human patients may have wider implications for the validity of using mouse models to define human iNKT-cell selecting ligands. Venous blood was collected in EDTA tubes and maintained at room temperature for a maximum of 60 h prior to cell separation. Control samples were obtained after informed consent/assent and ethical approval from centres in the United Kingdom or United States. NPC1 patient samples were obtained from patients from centres in the United Kingdom, United States, and Germany with informed consent or assent. Heterozygote samples were obtained with informed consent/assent from the parents of affected patients or known carrier siblings. Peripheral blood was loaded onto an equal volume of Histopaque 1077 (Sigma-Aldrich) and spun at 400 × g for 30 min at room temperature. The mononuclear cell layer was isolated and washed twice with Dulbecco’s PBS (D-PBS), counted and viability determined using Trypan blue. Antibodies were used according to the manufacturers instructions and the following clones were used CD14 allophycocyanin-H7 (MΦP9), CD1d PE (CD1d42), CD19 PE-Cy™7 (SJ25C1), CD161 allophycocyanin (DX12), CD3 Pacific Blue™ (UCHT1), CD4 allophycocyanin-H7 (SK3), CD8α PerCP-Cy™5.5 (SK1) Invariant NK T-cell PE (6B11) and CD45 FITC (2D1) (all from BD Biosciences).

From this paper, we extracted an affinity-balanced

set of 12 peptide pairs of immunogenic and nonimmunogenic binders, and tested both affinity and stability of their interaction with HLA-A*02:01. By and large, we confirmed the reported affinity data. Importantly, we found a highly significant correlation between high stability and immunogenicity (a half-life of 14 h for the immunogenic binders versus 3 h for the nonimmunogenic binders, p = 0.0007). Thus, this affinity-balanced reanalysis of the unbiased data reported by Sette and colleagues confirms that the stability of pMHC-I complexes contributes to the definition of immunogenicity, and that stability is a better indicator of immunogenicity than affinity is. This experimental analysis was subsequently corroborated by a bioinformatics-driven analysis. Our data suggest that the description and relative contribution of antigen this website processing and presentation events needs to be redefined. Nonimmunogenic binders are usually considered to be the result of “holes in the T-cell repertoire.” However, a failure to achieve stable interaction with MHC may be considered an alternative mechanism of lacking immunogenicity, as a “hole in the stably bound MHC repertoire”

mechanism, which would go unnoticed when solely addressing the affinity of peptide-MHC-I interactions. This may account for as much as 30% of these instances of lacking immunogenicity and it follows that a method

to predict the stability of pMHC-I complexes might support computational CTL epitope discovery. science Finally, both our experimental and bioinformatics-driven Alpelisib analysis suggested that the lack of stability of HLA-A*02:01 binding occurred when the P2 anchor residue was not optimal. Although both threonine and glutamine can be found in P2 of high-affinity binding peptides, they lead to a seven to tenfold reduction in stability compared to the optimal leucine. Thus, it would appear that one anchor might be sufficient for binding, whereas two anchors might be needed to obtain stable MHC-I interaction. This is reminiscent of a previous suggestion that the different pockets of the MHC-II can be seen as interacting with peptide independently, and that destabilizing any of the pockets individually may lead to peptide dissociation [[39]]. Thus, pMHC-I stability studies should help elucidating how peptide bind and remain bound to MHC-I, and how MHC-I matures and eventually becomes a bona fide CTL target. Peptides were synthesized by Schafer-N (Copenhagen, Denmark) by Fmoc chemistry and HPLC purified to at least more than 80% (usually >95%), analyzed by HPLC and MS, and quantitated by weight. Synthetic genes encoding MHC-I heavy chains were generated as previously described [[40, 41]]. Briefly, genes encoding MHC-I heavy chains truncated at position 275 (i.e.

Romanzi et al. studied patients with persistent urinary frequency, urgency and/or UUI.They found that involuntary detrusor contractions were observed in 100% of the neurologically impaired patients, compared with 76% of the neurologically intact patients.21 Hashim and Abrams evaluatedadult patients with or without OAB symptoms by complete storage symptoms data and urodynamics. They found that patients with urgency had more DO than those without urgency (78.6% vs. 46.5%, p < 0.001), and patients with UUI had more DO than those without UUI (84.2% vs 59.8%, p < 0.001).7 In

the sub-analysis, they found that 69% of men and 44% of women with urgency (OAB dry) had DO, while 90% of men and 58% of women with urgency and urgency incontinence (OAB wet) had DO. GS-1101 solubility dmso We also found that the incidence of urodynamic DO in women with OAB was significantly

lower than that in men (74.4% vs 98%) and the incidence of IBS was higher GSK-3 signaling pathway than men (11.2% vs 1.5%). The gender difference in urodynamic DOin OAB patients could be due to anatomical difference between men and women, causing increased urge sensation during their daily life and mimicking OAB symptoms.18 In a recent study analyzing urodynamic results in OAB women with and without urodynamic DO, Guralnick et al. found patients with DO were more likely to have abnormal sensation, lower volume for strong desire and urgency and more UUI episodes.22 Haylen et al. found sensory urgency is a common symptom and until sensory urgency may be an earlier form of DO.12 Interestingly, Malone-Leeet al. demonstrated that the efficacy of combination of oxybutynin and bladder training for OAB symptoms was not different in groups with or without DO.23 Sensory urgency

or IBS might share the same pathophysiologies with DO, which include myogenic theories and myofibroblast activity, as well as an increasing appreciation of urothelial afferent function.24,25 Therefore, although urodynamic study is a well- established method for diagnosing the presence of DO, a less invasive way to diagnose OAB and assess therapeutic outcome in patients with OAB still needs to be found. OAB is a highly prevalent urinary dysfunction, with considerable economic and human costs. Clinical diagnosis of OAB is still based on subjective symptoms. A new accurate, objective and noninvasive test to diagnose OAB and assess therapeutic outcome is lacking. Recent studies in lower urinary tract dysfunction (LUTD), particularly in OAB patients, indicate that urinary proteins such as neurotrophins, prostaglandins and cytokines are altered, and such changes could be used as potential biomarkers of OAB. NGF is a small secreted protein which induces the differentiation and survival of particular target neurons (nerve cells).

However, these cells were also identified in normal mucosa. In fact, healthy oral and nasal mucosae are in permanent contact with foreign bodies and microorganisms, maintaining baseline immune surveillance even in the absence of clinical signs of inflammation. Expression of NOS2 varied greatly. Despite the lack of a significant difference, nasal lesions tended R428 to express more NOS2. An inverse correlation was observed between the expression of NOS2 and the presence of parasites. Similar results have been reported for cutaneous lesions (14). In addition, nitric oxide – the product of NOS2 – has been associated with tissue destruction

(25) and may contribute to the formation of the extensive lesions generally observed in ATL mucosa as well as in other infections (18). Low expression of NOS2 has been previously observed in healthy tissues (26). Neutrophils were detected in all groups studied, but their number was significantly higher in ATL lesions. Studies have demonstrated higher parasite burdens in mice depleted of neutrophils and infected with Leishmania spp. (27,28).

Moreover, the importance of the formation of neutrophil extracellular traps during in vitro infection with Leishmania spp., and the presence of these cells in human lesions, has been demonstrated (15,29). Langerhans cells are normally found above the basal layer of the skin (30), oral mucosa (31) and nasal mucosa (32). We observed a similar Fulvestrant purchase distribution of these cells in the epithelium and a small number in the lamina propria of all tissues analysed. However, Modlin et al. (16) and Martinez-Arendes et al. (8) did not detect Langerhans cells in nasal mucosal leishmaniasis lesions. These apparently contradictory findings

may have various explanations, ranging from differences in the type of lesion and biopsy site to the source of the antibody used. Anacetrapib Cutaneous lymphocyte-associated antigen (CLA+) cells were frequently found inside vessels and adhered to the endothelium. The importance of CLA during migration and its location in the skin and mucosa has been demonstrated (23,33). CD62E and CLA showed a similar distribution and variable intensity in mucosal ATL, similar to cutaneous ATL (14). In our study, the number of CLA+ cells was twice as high in nasal ATL lesions when compared to C–N. This finding agrees with the description of an intense inflammatory process characterized by continuous cell migration producing the maintenance or constant increase in the local immune response. In contrast, a similar expression of CLA was observed in ATL and healthy oral mucosa. It might be explained by the particular conditions of microtrauma and constant exposure to infectious agents of supposedly healthy oral mucosa. As an aggravating factor, oral lesions are generally highly painful, a fact impairing adequate cleaning. In addition, the mouth can be considered a contaminated site.

Background: Listeria monocytogenes is a rare cause of peritonitis, usually occurring in the setting of cirrhosis or immunosuppression. Bortezomib manufacturer There are 12 published cases of Listeria monocytogenes peritoneal

dialysis peritonitis in the literature. The 10 patients on continuous ambulatory peritoneal dialysis and 2 with unknown method of peritoneal dialysis were all treated with intravenous or intraperitoneal antibiotics. We report a case occurring in an automated peritoneal dialysis patient, successfully treated with oral antibiotics. Methods: An 87 year old, non-immunosuppressed end-stage renal failure patient on automated peritoneal dialysis, presented with abdominal pain, bloating and diarrhoea after consuming a meal of sushi. She was systemically well and commenced

on empiric outpatient antimicrobial therapy with intraperitoneal vancomycin 2 g and gentamicin 80 mg. Peritoneal dialysate gram stain demonstrated gram positive rods, subsequently culture positive for Listeria monocytogenes. Her antibiotic therapy was changed to amoxicillin 1 g every eight hours orally and she completed total of 22 days of therapy. Her abdominal discomfort resolved and her peritoneal dialysate BMS354825 cleared. Results: Repeat dialysate culture one week following completion of antibiotic therapy confirmed resolution of peritonitis. Conclusions: Oral antimicrobial therapy may be effective in treatment of Listeria monocytogenes peritoneal dialysis peritonitis in the systemically well patient. 292 UNUSUAL BLEEDING

IN THIN GLOMERULAR BASEMENT MEMBRANE DISEASE A LEE, J SEVASTOS St Vincent’s Hospital, Sydney, NSW, Australia Aim: We present a case of thin glomerular basement membrane (GBM) disease with unusual manifestations of haematuria, haemoptysis and peritoneal bleeding. Background: Thin GBM disease is caused by a defect of collagen, occasionally Rebamipide associated with loin pain haematuria syndrome. It is considered a disease affecting only the renal tract. There are only few case reports of haemoptysis associated with this condition but there is no literature suggesting bleeding elsewhere. Methods: A young patient presented age 16 with recurrent severe abdominal pain over many months. Laparoscopy for appendicectomy demonstrated no appendicitis but a small amount of blood was found in the pelvis. She subsequently developed intermittent macroscopic haematuria. Cystoscopy showed mild to moderate mucosal bladder erythema and trabeculation, possibly interstitial cystitis. Repeat laparoscopy again noted the presence of free blood in the pelvis. There was no endometriosis and sexually transmitted infection screen was negative. Endoscopy revealed moderate chronic fundal gastritis and colonoscopy to investigate rectal bleeding found a rectal hyperplastic polyp.

In addition, as our study suggests, IL-15 is unlikely to be the only stimulus that determines the extent of NK-cell expansion. We found that stimulation with IL-15 had a profound impact on NK cells, but that the kinetics and the extent of activation were readily enhanced by addition of other cytokines. Addition of SCF accelerated the IL-15 induced downregulation of c-kit, whereas the combination of IL-7 and IL-15 downregulated

CD127 even more profoundly than IL-15 alone (data not shown). Hence, SCF, buy Ulixertinib IL-2, IL-7 and perhaps multiple other stimuli present in the plasma of transplanted patient may modulate the effect of IL-15 and conceal the direct relationship between IL-15 and the extent of NK-cell expansion. Our data show that the “aberrant” NK-cell phenotypes as well as the reversed CD56bright/CD56dim observed after HSCT 27–30, 32, 33 can be attributed

www.selleckchem.com/products/Rapamycin.html to activation and subsequent expansion of CD56bright. Because we found no correlation between the number of ptCD56bright and CD56dim, we find it unlikely that the bulk of ptCD56bright are NK cells maturing toward CD56dim. Moreover, we observed that patients with high numbers of ptCD56bright could have low numbers of CD56dim for a prolonged period of time and that the number of ptCD56bright could remain high for as long as 6 months in patients with slow T-cell recovery (data not shown). Obviously, our data do not exclude that part of ptCD56bright mature into CD56dim nor suggest that CD56bright circulating in peripheral blood and lymph nodes cannot be the precursors of PRKACG CD56dim. They do show, however, that the level of expression of c-kit and CD127, two receptors often used as markers to define distinct NK-cell lineages 37, 38 or different NK-cell subsets 4, 9, 12, 15, 17, 19 may simply reflect the cytokine level of the environment they have been isolated from and that caution should be taken to interpret low c-kit- or CD127-levels as proof of maturation of CD56bright toward CD56dim. Patients (eleven AML, five ALL, six CML, one CLL, two MDS, two HL and two NHL) received PBSC from related (n=14) or unrelated (n=15) donors after standard intensity (n=24)

or reduced intensity conditioning (n=5) combined with ATG if the donor was unrelated. Twenty-three patients received grafts depleted by Alemtuzumab in vitro followed by T-cell add-back on day+1 as described previously 53. GvHD prophylaxis was by Cyclosporine combined with Methotrexate or with Mycophenolate Mophetil after reduced intensity conditioning. Sequential analysis of mixed chimerism 54 showed that all hematological lineages were of donor-origin except for T cells that could be of mixed origin during the first 6 months. Sixteen healthy individuals donating blood at our Blood Transfusion Center served as normal controls. Our institutional ethics committee approved the research and patients gave informed consent.

On day 6, the NF-κB inhibitor-treated and -untreated im-DCs were incubated with LPS or TNF-α to see if they could be induced to mature. Comparative study of the expression of surface molecules on LPS-induced mature DCs (m-DCs) that might be related to allostimulation found that AZM, added at 50 µg/ml on days 0, 3 and 6, inhibited the expression of MHC class II

and co-stimulatory molecules (CD40, CD80 and CD86) when Vit. D3 was used as a positive control [30] (Fig. 1a). Conversely, the PPAR-γ activator, ACE inhibitor and clarithromycin did not suppress the expression of MHC class II or co-stimulatory molecules (Fig. 1a). When the expression levels were compared on the basis of the mean fluorescence intensity (MFI), the expression of MHC class II and co-stimulatory molecules but not CD80 were decreased significantly in a dose- and time-dependent manner (Table 1). TLR-4 GSK-3 inhibitor Obeticholic Acid manufacturer expression was also decreased in AZM-treated im-DCs stimulated with TNF-α (Fig. 1b). The MFIs of TLR-4 of

control m-DCs and AZM-treated m-DCs were significantly different (13·39 ± 1·07 versus 8·56 ± 0·47; P < 0·01, n = 3) (Fig. 1b). Similar to the results for expression of MHC class II and co-stimulatory molecules, the PPAR-γ activator, ACE inhibitor and clarithromycin did not affect expression of TLR-4 (Fig. 1c). We also confirmed that the vehicles used to dissolve the NF-κB inhibitors Digestive enzyme did not affect the expression of these antigens and showed no toxicity when we added equal amounts of them to culture wells as controls (data not shown). Morphologically, AZM-treated im-DCs (Fig. 1d) were similar to control im-DCs

(Fig. 1e). However, in the case of LPS-induced m-DCs, AZM treatment resulted in less prominent dendrite formation, with a round nucleus (Fig. 1f), compared with the control cells (Fig. 1g). To determine whether AZM might affect the functions of DCs, we first compared IL-12p70 production by AZM-treated and -untreated im-DCs stimulated with LPS. As shown in Fig. 2a, the IL-12p70 concentration was significantly lower in the supernatant of AZM-treated im-DCs (P < 0·001). We next asked whether AZM might affect the allogeneic T lymphocyte stimulatory capacity of DCs. To address this question, we performed MLR experiments. [3H]-Thymidine incorporation was suppressed significantly when allogeneic T lymphocytes were stimulated with m-DCs treated with 50 µg/ml of AZM, causing up to 27% reduction of the allostimulatory capacity (Fig. 2b). We also investigated the secretion levels of IFN-γ and IL-10 in the MLR supernatant by enzyme-linked immunosorbent assay. IFN-γ was reduced by 31% when allogeneic T lymphocytes were stimulated with AZM-treated m-DCs compared to untreated m-DCs, indicating that AZM-treated m-DCs decreased Th1 polarization (Fig. 2c).

In the different assays discussed below, the phagocytes must be incubated with a certain stimulus to activate the NADPH oxidase in these cells, because in resting phagocytes this enzyme is inactive. Frequently used stimuli are phorbol myristate acetate (PMA, a soluble, receptor-independent stimulus of protein kinase

C), serum-treated zymosan particles BIBW2992 in vivo (a particulate stimulus that binds to Fc-gamma receptors and complement receptor-3 on the cell surface) and the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP), binding to fMLP receptors on the cell surface and activating the NADPH oxidase when the cells have been ‘primed’ with platelet-activating factor (PAF). Oxygen consumption can be measured with an oxygen electrode [13], but this is a time-consuming and relatively insensitive method that is no longer used for CGD diagnostics. It is the most quantitative method of oxidase measurements, but for CGD diagnosis a simple yes (activity) or no (no activity) usually suffices. Assays for superoxide or Selleck Ensartinib hydrogen peroxide are generally employed instead. Superoxide generation can be measured by its ability to reduce ferricytochrome c, nitroblue tetrazolium, isoluminol

or lucigenin. The ferricytochrome c reduction is followed spectrophotometrically at 550 nm, because the difference in extinction coefficients of ferricytochrome c (0·89 × 104 M/cm) and its reduction product ferrocytochrome c (2·99 × 104 M/cm) is the largest at that wavelength. The contribution of superoxide to the reduction process must be quantified by adding superoxide dismutase (SOD). This enzyme catalyzes the second reaction shown above, JAK inhibitor and thus prevents superoxide

from reacting with ferricytochrome c. Any reduction of ferricytochrome c in the presence of SOD is superoxide-independent and must therefore be subtracted from the total reduction to obtain the superoxide-dependent contribution. The assay relies upon the excretion of superoxide by activated phagocytes because it takes place extracellularly, in the medium surrounding the cells. A detailed protocol for this reaction, with isolated neutrophils activated with PMA in a microtitre plate, can be found in [14]. Nitroblue tetrazolium (NBT) is a pale yellow dye that can be reduced by superoxide to the black, insoluble formazan. This reaction takes place inside activated phagocytes, thus leaving cells with an active NADPH oxidase stained by formazan deposits that cannot leave the cells. This property has made NBT an ideal agent to judge the oxidase activity of individual cells, which is especially useful for carrier detection of X-linked CGD (see section Oxidase activity or protein expression in single cells). CGD patients usually show no or very little formazan deposition in any cell [15].

The aim of the current study was to validate this result and determine the presence of VEGFR-2 activity in paediatric pilocytic astrocytoma as the main VEGFR in terms of mitogenic signalling. In addition, the localization of VEGFR1–3 mRNA expression was assessed. Methods: VEGFR-2 phosphorylation Neratinib nmr was determined by adopting a proximity ligation assay approach. Enrichment of endothelial

markers and VEGFRs in tumour endothelium was determined by quantitative polymerase chain reaction (qPCR) analysis of laser-microdissected blood vessels. Results: Proximity ligation assays on tumour cryosections showed the presence of phosphorylation of VEGFR-2, which primarily localized to vascular endothelium. qPCR analysis of endothelial markers and VEGFRs showed a 13.6-fold average enrichment of VEGFR-2 expression in the laser-microdissected endothelium

compared to whole tumour. Also the expression of VEGFR-1 and -3 was highly enriched in the endothelium fraction with an average fold-enrichment of 16.5 and 50.8 respectively. Conclusions: Phosphorylated VEGFR-2 is detected on endothelial cells in paediatric pilocytic astrocytoma. Furthermore, endothelial cells are the main source of VEGFR1–3 mRNA expression. This suggests a crucial role for VEGF/VEGFR-induced angiogenesis in the progression and maintenance of these tumours. “
“Reticulons are a group of membrane-bound proteins involved in diverse cellular functions, and are suggested to act as inhibitors of β-secretase enzyme 1 (BACE1) activity that cleaves amyloid Lumacaftor precursor protein. Reticulons are known to Palbociclib cell line accumulate in the dystrophic neurites of Alzheimer’s disease (AD), and studies have suggested that alterations in reticulons, such as increased aggregation, impair BACE1 binding, increasing amyloid-β production, and facilitating reticulon deposition in dystrophic neurites. To further characterize the cellular distribution

of reticulon, we examined reticulon-3 expression in cases of AD, Parkinson’s disease, and diffuse Lewy body disease. A more widespread cellular distribution of reticulon-3 was noted than in previous reports, including deposits in dystrophic neurites, neuropil threads, granulovacuolar degeneration, glial cells, morphologically normal neurons in both hippocampal pyramidal cell layer and cerebral neocortex, and specifically neurofibrillary tangles and Lewy bodies. These results are compatible with reticulon alterations as nonspecific downstream stress responses, consistent with its expression during periods of endoplasmic reticulum stress. This emphasizes the increasing recognition that much of the AD pathological spectrum represents a response to the disease rather than cause, and emphasizes the importance of examining upstream processes, such as oxidative stress, that have functional effects prior to the onset of structural alterations.