L-3 expressed on AP-61 cells may be involved in

the interaction with DENV. Seppo et al. found two GSLs, zwitterionic and acidic GSLs, in the Drosophila melanogaster embryo (21). However, Tyrosine Kinase Inhibitor Library high throughput they could not detect Nz3, which is similar to L-3. Moreover, nLc4Cer has not so far been detected in neutral GSLs of AP-61 cells. Since insect cells do not contain β-N-acetylgalactosaminyl-transferase, which produces Gal β-(22, 23), it can be deduced that nLc4Cer will not be found in these cells. In comparing the GSLs that can bind to dengue virus on TLC plates, the β-GlcNAc residue was noted to have a similar carbohydrate moiety to those of L-3 and nLc4Cer. A previous study reported that β-HexNAc is important in the process of DENV binding to host cells (7). The core structure of two DENV-2-binding

GSLs, L-3 and nLc4Cer, which are predominantly found in GSLs, is different from those of N- and O-linked glycoproteins. The Dinaciclib cell line host range of DENV is restricted to only humans and mosquitoes. Since DENV is propagated in mosquitoes and characteristically transmitted to humans, GSLs such as L-3and nLc4Cer may play important roles in virus transmission. This paper was supported and funded by Mahidol University and a Southeast Asian Ministers of Education Organization/Regional Tropical Medicine and Public Health scholarship. Part of this work was supported by Core Research and Technology (Japan Science and Technology Agency), Japan and the Department of Virology, Armed Forces Research Institute of Medical Sciences, Thailand. “
“Transplantation is a successful treatment for end-stage organ failure. Despite improvements in short-term outcome, long-term survival remains suboptimal because of the morbidity and mortality associated with long-term use of immunosuppression. There is, therefore, a pressing need to devise protocols that induce tolerance in order to minimize or completely withdraw immunosuppression in transplant recipients. In this review we will discuss how regulatory

T cells (Tregs) came to be recognized as an attractive way to promote transplantation tolerance. We will summarize the preclinical data, supporting the importance 4-Aminobutyrate aminotransferase of these cells in the induction and maintenance of immune tolerance and that provide the rationale for the isolation and expansion of these cells for cellular therapy. We will also describe the data from the first clinical trials, using Tregs to inhibit graft-versus-host disease (GVHD) after haematopoietic stem cell transplantation and will address both the challenges and opportunities in human Treg cell therapy. Other Articles Published in this Series T cell depletion in paediatric stem cell transplantation. Clinical and Experimental Immunology 2013, 172: 139–47. Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now? Clinical and Experimental Immunology 2013, 172: 148–57.

Diameters were determined for n = 72 beads and were 136 µm (range 74–205 µm) for LB and 40 µm (range 15–85 µm) for SB (Fig. 1a). Using the formula for sphere volume = 4/3 ×π×r3, the LB were found to have a mean volume of 1 317 000 µm3 compared to 34 000 µm3 for the SB, giving a ratio difference in volume of 38·7 between LB and SB. Using the formula for sphere surface area = 4 × p ×r2, the LB were found to have a surface area of 58 107 mm2 compared to 5027 mm2 for the SB, giving a ratio difference in surface area of 11·6 between selleck kinase inhibitor LB and SB. Because both groups received the same amount of bacteria and alginate, this provides a larger total surface area of the SB of 3·3 (38·7/11·6 = 3·3).

In addition, the volume of alginate in the two bead suspensions was adjusted to ensure equal volumes of alginate in the two groups. At day 1 after challenge, a significantly higher number of CFUs was observed in the lungs of SB group compared to the LB group (P < 0·003) (Fig. 2). At days 3, 5 and 6 no significant differences in quantitative bacteriology were observed between the two groups. P. aeruginosa could be cultured from the majority of mice at all time-points (Fig. 2). Four mice from each group were killed 2 h after infection, and lungs examined for

number of CFUs to confirm that the infection dose was equal in the two groups. No significant differences were observed in CFUs 2 h after challenge (Fig. 2). As expected, a PMN-dominated KU-57788 cell line inflammation was observed in all mice at day 1 after infection (Table 1). However, in the SB group the inflammation was located exclusively endobronchially, in contrast to a partially mixed localization in the LB group (Table 1). In the SB group this shifted

significantly to a mixed localization or exclusively parenchymal localization on days 2/3 after challenge (P < 0·005, Table 1), and in general was paralleled by a more peripheral presence of the bacteria in the alveoli of the SB group. For the SB group, a significantly faster resolution of inflammation at days 5/6 compared to the LB group was observed (P < 0·03, Table 1). For both groups together, a significant increase in degree of inflammation from day 1 to days 2/3 was observed (P < 0·01, Table 1). However, the difference between the two groups for this observation did not reach significance. C59 in vivo The area of the biofilm-like structures identified by Alcian blue staining were significantly smaller in the SB group compared to the LB group at day 1 and days 2/3 (P < 0·001, Figs 3 and 4). In accordance, the area of the airways in which biofilm-like structures were identified were significantly smaller in the SB group compared to the LB group at days 2/3 (P < 0·002, Figs 3 and 4). The number of identified biofilm-like structures was 137 in the LB group versus 308 in the SB group. PNA-FISH and DAPI staining confirmed the presence of P. aeruginosa in the biofilm-like structures (Fig. 5).

2d). Thus, although the macroscopic inflammation of colonic tissue was similar in both DSS-treated wild-type and Bcl-3−/− mice, the clinical indices of the DSS-induced colitis, in particular weight loss, were reduced significantly Selleck NU7441 in Bcl-3−/− mice. To investigate further the differences in DSS-induced colitis between wild-type and Bcl-3−/− mice, we performed a histological examination of distal colon tissue sections from untreated and DSS-treated wild-type and Bcl-3−/− mice (Fig. 3a). No differences were observed between untreated wild-type and untreated Bcl-3−/− distal colonic tissue samples by H&E staining. Both wild-type

and Bcl-3−/− mice displayed normal epithelial architecture with intact goblet cells and BAY 57-1293 manufacturer crypts with no discernible

inflammatory influx. DSS treatment of wild-type mice induced a dramatic alteration in the colonic mucosal tissue with extensive oedema, large cellular infiltrates and a severe loss of tissue organization with destruction of crypts and loss of goblet cells. Although histological analysis revealed similar levels of oedema and cellular infiltrates in Bcl-3−/− mice, there was significantly less destruction of the tissue architecture following DSS treatment (Fig. 3a). Quantitative histopathological analysis of the distal colon tissue from DSS-treated Bcl-3−/− mice revealed significantly reduced epithelium damage and loss of tissue architecture compared to wild-type mice (Fig. 3b). However, there were no significant differences in the extent of inflammation (Fig. 3c) and the degree of cellular Low-density-lipoprotein receptor kinase infiltration and oedema (Fig. 3d) between DSS-treated wild-type and Bcl-3−/− mice. This histological analysis

provides insight into the reduced weight loss and overall clinical disease score observed in DSS-treated Bcl-3−/− mice relative to wild-type mice, which would appear to result from an intact or regenerated epithelium rather than reduced leucocyte infiltration. Although histological analysis showed similar levels of oedema and leucocyte infiltration in DSS-treated wild-type and Bcl-3−/− mice, it is possible that the inflammation may be qualitatively different between these groups. In order to characterize the inflammation associated with DSS-induced colitis in Bcl-3−/− mice, we next measured inflammatory gene expression in distal colon tissue from untreated and DSS-treated wild-type and Bcl-3−/− mice using qRT–PCR. Surprisingly, although Bcl-3 has been described previously as a negative regulator of Toll-like receptor-induced proinflammatory gene expression, we found no significant difference in the expression of TNF-α, IL-6, CXCL1 and IL-1β between DSS-treated wild-type and Bcl-3−/− mice (Fig. 4a). Recent studies have identified a protective role for the cytokines IL-17A and IL-22 [22-24] in DSS colitis by inducing anti-bacterial peptide expression and epithelial cell regeneration in the colon.

, 1998). The Trojan horse mechanism of transport across BBB is considered to play a crucial role in the pathogenesis of viral meningitis in the late phase of AIDS. This model has gained rapid favor; however, recent studies change this model by showing that the vast majority of virions transmitted in trans originate from the plasma membrane rather than from intracellular vesicles (Cavrois et al., 2008). The mechanisms of BBB disruption during retroviral-associated pathologies are not fully understood yet. Most of the studies are focused on the effect

of soluble molecules secreted by infected lymphocytes on BBB functions and intercellular TJ organization. In case of HIV infection, the viral protein Tat has been shown to induce cell apoptosis and disruption of the TJs (Andras et al., 2003). In short, Tat-mediated downregulation MAPK Inhibitor Library of claudin-5 plays an important role in altered integrity of BMEC that aids viral transport across BBB (Andras et al., 2005). West Nile virus (WNV)-associated encephalitis is characterized by disruption of the BBB, enhanced infiltration of immune cells into the CNS, microglial activation, inflammation, and eventual loss of neurons (Glass et al., 2005; Sitati et al., 2007). WNV gains entry into the CNS via the transcellular pathway, without compromising

the BBB integrity instead Roxadustat clinical trial of paracellular pathway (Verma et al., 2009). Tick-borne encephalitis

(TBE) virus causes severe encephalitis with serious sequel in humans. The mechanisms underlying how TBEV gains access to the CNS are not completely elucidated. There are several hypothetical routes for TBEV traversal across BBB. These include (i) cytokine-mediated BBB breakdown, (ii) “Trojan horse” theory, and (iii) viral entry into the BMECs, transcytosis, and the release of virus into the brain parenchyma (Ruzek et al., 2011). Proteins from microbial pathogens are the dominant virulence factors mediating entrance to the CNS; however, various nonproteinous microbial components including lipopolysaccharide, LTA, glycolipids, and hyaluronic acid contribute to breakdown of the BBB. Lipooligosaccharide on the outer membrane is an important inflammatory agent Mirabegron in the CSF. Recent studies have demonstrated that lipooligosaccharide and lipopolysaccharide containing outer membrane vesicles provoke meningeal inflammation, increase concentration of leukocytes, and change permeability of the BBB (Cope et al., 1990). Hyaluronic acid of C. neoformans capsule facilitates the transport via BBB (Jong et al., 2007). Several hyaluronic acid receptors have been identified on various ECs; however, the only receptor on BMEC interacting with hyaluronic acid is CD44, the most common hyaluronic acid receptor in vertebrates. This interaction initiates the events of the entry at the BMEC membrane rafts (Jong et al., 2008).

01). Conclusion: Our studies confirmed the role of Gd-IgA1-IgG IC in the pathogenesis of IgAN and induction of proteinuria and hematuria.

Furthermore, the Gd-IgA1-IgG IC may bind to glomerular endothelial cells and induce release of pathogenic cytokines and chemokines. SUZUKI HITOSHI1, SUZUKI YUSUKE1, MAKITA YUKO1, YANAGAWA HIROYUKI1, JULIAN BRUCE A2,3, NOVAK JAN3, TOMINO YASUHIKO1 1Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine; 2Departments of Medicine, selleck chemicals llc University of Alabama at Birmingham; 3Departments of Microbiology, University of Alabama at Birmingham Introduction: IgA1 in circulating immune complexes and mesangial deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated, galactose-deficient in O-glycans (Gd-IgA1), and is bound to anti-glycan IgG/IgA autoantibodies. However, the origin of cells producing Gd-IgA1 and the autoantibodies is not certain. Upper respiratory tract infections and tonsillitis are frequently associated with clinical presentation and exacerbation of IgAN, suggesting a link with disease pathogenesis. In some patients, tonsillectomy and glucocorticoids (TSP) may slow disease progression this website in early clinical stages. Therefore, we assessed whether

tonsillar cells produce Gd-IgA1 or anti-glycan autoantibodies. Methods: Tonsillar

cells obtained from 29 patients with IgAN were cultured 72 hours. Gd-IgA1 and anti-glycan IgG secreted by these cells were measured by ELISA. Proteinuria and hematuria, and serum levels of Gd-IgA1, Gd-IgA1-specific IgG and IgA, and IgG-IgA immune complexes (IC) were measured before and Rho after TSP. Results: Proteinuria and hematuria improved after TSP (P < 0.05). Eighteen of 29 patients had proteinuria less 0.3 g/g and 5 red blood cells/HPF after TSP (Remission group). Eleven patients did not clinically improve (non-Remission group). Serum levels of Gd-IgA1, Gd-IgA1-specific autoantibodies, and IgG-IgA IC decreased during glucocorticoid therapy after tonsillectomy (P < 0.01). The rates of decrease in the levels of Gd-IgA1, Gd-IgA1-specific antibodies and IgG-IgA IC were greater in the Remission group (P < 0.01). Tonsillar cells from Remission group produced more Gd-IgA1 and anti-glycan IgG than those from non-Remission group (P < 0.01). Conclusion: Tonsillar cells may contribute to the circulating Gd-IgA1 and anti-glycan IgG in patients with IgAN. These biomarkers may be useful for guiding therapy of IgAN. YAMADA KOSHI1,2, HUANG ZHI-QIANG1, RASKA MILAN1,3, REILY COLIN R.1, SUZUKI HITOSHI1,2, MOLDOVEANU ZINA1, KIRYLUK KRZYSZTOF4, SUZUKI YUSUKE2, TOMINO YASUHIKO2, GHARAVI ALI G.4, WILLEY CHRISTOPHER D.1, JULIAN BRUCE A.

8 mmol/L) and rapidly evolving acute

kidney injury due to acute tubular necrosis (ATN; initial creatinine 120umol/L, peak at 1210umol/L on day 4 post-diving accident). The diagnosis of ischaemia-induced ATN was supported by a high urinary fractional sodium excretion of 5.5%, elevated LDH (486U/L [125–250]) and a MAG3 scan in keeping with ATN. The absence of myoglobinuria and only moderately elevated creatine kinase (maximum 893U/L [30–170]) made rhabodmyoloysis-induced TGF-beta inhibitor ATN unlikely. He received supportive care with intravenous hydration, sodium bicarbonate and 100% oxygen followed by 7 sessions of hyperbaric therapy and recovered fully without needing dialysis. Conclusions: Arterial air embolism occurs when expanding gas ruptures alveolar capillaries (pulmonary barotrauma) and enters the arterial circulation as a result of rapid decompression. Clinical manifestations depend on the site of embolization and usually include neurological and respiratory symptoms but can also

involve the muscles, skin, mesenteric circulation and as shown in this case the kidneys. The diagnosis is made on clinical grounds since gas bubbles are rarely detectable on imaging. Best first aid for decompression illness is 100% oxygen therapy and supportive care but early transfer to a hyperbaric treatment unit is important as symptoms may evolve over time as in our patient. 277 HYPERKALEMIA INDUCES FAILURE OF PACEMAKER FUNCTION IN HEMODIALYSIS PATIENT N AUNG, S MAY Tamworth Base Hospital, New South Wales, Australia Background: Hyperkalemia may cause cardiac pacemaker Panobinostat malfunctioning due to a reduction of the electronegativity of the resting myocardial potential. Both sensing and capture mechanisms could be temporarily affected, with possible life-threatening effects. Case Report: Mr. DT, 50 years old male with background history of End Stage Renal Failure due to diabetic nephropathy on maintenance hemodialysis, Aortic Valve Replacement, Pacemaker for third degree AV block presented to ED in a small rural hospital with lethargy and unwell. BP 82/50 mmHg, HR 22/min. ECG showed significant bradycardia

20/min with failure of rhythm to capture the pacing. Arrangement was made for urgent transfer to Metropolitan unit with pacemaker malfunction. Subsequent Nintedanib (BIBF 1120) result: K 7.6 mmol, BSL 52.8 mmol. Repeat ECG show similar finding with no classic hyperkalemia changes. Patient was treated with usual medications for hyperkalemia and commenced on insulin infusion. At the same time, Haemodialysis was commenced. After 30 minutes on dialysis, patient’s vital sign improved to BP 100/70 mmHg, HR 65/min with ECG showing normal ventricular paced rhythm. Conclusions: Hyperkalemia is a cause of acute pacemaker malfunction without classical hyperkalemia ECG change due to a failure of pacemaker sensing and capturing. Acute treatment of hyperkalemia will restore pacemaker function.

At any one time, a large fraction of the total T-cell pool in a healthy individual is distributed in nonlymphoid tissues 6–8. These lymphocytes have the phenotype of effector memory cells and most

are thought to be cells in transit through tissues, on their way back to the bloodstream. As reviewed here, it now appears that some of these peripheral memory cells, so-called tissue-resident memory T cells, have permanently left the circulating memory pool and have taken up residence in nonlymphoid tissues. In some cases, the rationale for this is clear: having dealt with an infection at a particular site, the T cells stay on site to quickly deal with a subsequent appearance of antigen such as would occur following the recrudescence of a latent infection. This view is most Selleck ICG-001 simply applied to recent findings, following skin or mucosal infection with herpes virus and the subsequent latent infection of the innervating sensory

ganglia. From an initial site of entry such as skin or other epithelial surfaces, HSV-1 infects local nerve endings and is carried to the innervating sensory ganglia by Bafilomycin A1 mouse retrograde axonal flow where the virus can remain within neurons in various degrees of dormancy depending on the virus and the host species 9. In mice, the virus may be retained for the lifetime of the animal in infected neurons without full recrudescence at the initial site of infection. Virus-specific CD8+ T cells are important in controlling the early replication of the virus both at the site of entry and in the infected ganglia. However, in addition to this acute role, HSV-specific CD8+ T cells remain in the ganglia long after viral replication ceases. Many of these resident T cells express markers associated with recent

antigen activation such as CD69 and high levels of granzymes, and this is true even for those T cells specific for structural (glycoprotein) epitopes of the virus, not just for latency-associated antigens 10, 11. How far production of viral particles goes in the mouse is debated and in this situation tetracosactide constant or recurrent contact with MHC/peptide antigen may be involved in keeping the virus-specific T cells in the ganglion. When an HSV-1-infected ganglion is surgically excised and placed in organ culture or transplanted under the kidney capsule of uninfected mice, however, virus gene expression ramps up and, in the transplantation model, the virus-specific resident memory CD8+ T cells rapidly expand. This expansion has been shown to depend on the influx of inflammatory dendritic cells serving as antigen-presenting cells in the ganglion 12. Circulating HSV-1-specific memory T cells can also be recruited to the transplanted ganglion, but the kinetics of their response lags behind that of the resident memory cells 13.

[12, 13] In this review, current problems in screening, diagnosis, histological classifications, treatments and prognostic factors are discussed. As the initial presentation of BKVN is insidious, it is strongly recommended that kidney transplant patients are screened regularly for the early detection of viral replication. Both KDIGO and AST guidelines suggest screening for BKV with nuclear acid testing of plasma.[8-10] Unfortunately, the costs Y-27632 concentration associated with

screening all patients using quantitative PCR are high. Most Japanese and many American transplant centres perform urinary cytology tests initially, and then test plasma by PCR if they find urinary decoy cells consistently. AST also suggests urinary cytology for decoy cells, electron microscopy in search of viral aggregation, quantitative PCR of urine for >7 log10 copies/mL of BKV DNA[10] followed by PCR of plasma. They also emphasize the advantages of testing urine,

these being: a high negative predictive value, a longer window period (6–12 weeks) before viraemia and BKVN, and lower cost, especially for cytology tests. However, physicians should also consider the disadvantages, such as: a low positive predictive value, and delayed or lack of clearance after treatment, which can cause overly reduced immunosuppression and subsequent acute rejection. Another issue with screening for BKV is how often and how long patients should be screened. GSK2126458 stiripentol KDIGO guidelines suggest monthly screening for the first 3–6 months, then every 3 months until the end of the first year post-transplant; and adding tests when the patient shows an unexplained rise in serum creatinine and after anti-rejection treatment.[8] AST guidelines differ, recommending screening at least once every 3 months during the first 2 years, and then annually until the fifth year.[9, 10] The author reviewed 71 cases of biopsy-proven BKVN at the University of Pittsburgh Medical Center and found that the median time of diagnosis was 355 days post-transplant (range: 74–2856 days),[14] which is similar to results reported

by Vasudev et al. (median: 318 days; range: 48–1356 days).[15] These findings indicate that BKVN is a relatively later complication, and screening at least every 3 months during the first 2 year period seems appropriate to cover more than 80% of BKVN cases. Several studies have reported on protocols for the reduction of immunosuppression.[16-18] Currently, two strategies are recommended by AST, these being: (1) dose reduction of calcineurin inhibitor by 25–50% in one or two steps, followed by reducing the antiproliferative drug by 50%, followed by discontinuing the latter; and (2) reduction of the antiproliferative drug by 50%, followed by reducing calcineurin inhibitors by 25–50%, followed by discontinuing the antiproliferative drug.

Methods: Plasma, urine and kidney biopsy samples were obtained from 55 patients with LN. Histological features were classified according to the ISN/RPS LN criteria. Immunohistochemical analyses using anti-human CD68, CD163 or CD204 antibodies were performed for identification of macrophage phenotypes. Plasma and urine sCD163 concentrations were measured by ELISA. Results: Immunohistological analysis in LN glomeluli revealed more than 80% of CD68+ macrophages was merged with CD163+ cells. The number of glomerularCD68+, CD163+ or CD204+ macrophages was increased in association with severity

FK228 molecular weight of biopsy active index (BAI) score in LN. Interstitial CD68+, CD163+ or CD204+ macrophage infiltration correlated with eGFR. Urine sCD163 level showed stronger correlation with the number of glomerular CD163 positive cell counts (r = 0.535) and BAI score (r = 0.657) than plasma sCD163 levels with both of the above (r = 0.296 and r = 0.363, respectively). Conclusion: These results suggest that CD163+ or CD204+ macrophage is the dominant phenotype in kidneys of LN patients, and urine sCD163 level has a potential significance for estimation of disease activity in human LN. ITABASHI MITSUYO, TAKEI TAKASHI, MORIYAMA TAKAHITO, SATOU MASAYO, OCHI AYAMI, KATAOKA HIROSHI,

SHIMIZU ARI, NITTA KOSAKU Department of Medicine, Kidney Center, Tokyo Women’s SCH727965 solubility dmso Medical University, Tokyo Introduction: The Vasculitis Damage Index (VDI) defined as forms of damage occurring in patients with systemic

vasculitis. We conducted a retrospective study of 30 patients with MPA and RLV in ANCA associated vasculitis were included mostly in Japan. Methods: We examined the clinical data and the VDI for a period of 5 years. Results: The mean VDI score, which was 2.5 at 1 year after diagnosis, increased gradually 3.2, 3.5, 3.9 and 4.3 during 5 years after diagnosis. The organ damage based on musculoskeletal and ocular damage were Vildagliptin significantly increased during five year period (p = 0.001, p = 0.002). Items of damage were cataract (13%), hypertension (12%), diabetes mellitus (9%), and osteoporosis (6%). The cataract and the osteoporosis were significantly increased during five years (p = 0.0003, p = 0.02). The VDI score was significantly higher in relapse (n = 6) or MPA (n = 21) group than non-relapse (n = 24) or RLV (n = 9) group at 5 years (p = 0.02, p = 0.03). In addition, we found a correlation between the VDI score at 5 years and BVAS at diagnosis (p = 0.04, r = 0.4). Conclusion: The VDI was found to be a useful tool for determining damage caused by disease and its treatment. The individual contributions of the VDI score may also be applied in treatment decisions.

These molecules enter target cells (for example, infected

or tumour cells) through P pores and induce apoptosis. The aim of this study was to investigate P expression in lymphocyte subpopulations in BPH and PCa tissue. In addition, the frequency of P-expressing T lymphocytes buy ABT-199 and NK and NKT cells isolated from peripheral blood and prostate tissue of patients with BPH and PCa was determined. The results thus obtained were compared with those of a control group containing healthy subjects. Patients and control groups.  Peripheral blood and prostate tissue samples were collected from 20 patients (ages 62–73; mean: 67 years) undergoing radical prostatectomy because of PCa in the Clinic of Urology, Clinical Hospital Centre Rijeka in Rijeka, Croatia. Histopathological analysis of named prostate tissue samples confirmed that all samples were carcinomas with a differentiation grade according to Gleason of 6–9. The blood samples and tissues from patients with BPH were acquired form 20 patients (ages 56–70; mean: 63 years) who underwent transvesical prostatectomy. Peripheral blood was collected from 18 age-matched subjects (ages 57–62; mean: 59 years) that comprise control group. This age-matched subjects first underwent control examination and routine laboratory analyses, including prostate-specific antigen check details (PSA) values. The examination of control group was performed as a part of preventive medical programme conducted by local authorities.

The exclusion criteria for control subjects

were PSA values <4 ng/ml, and absence of lower urinary tract syndrome. Additionally, the exclusion criteria for all the subjects enrolled in the study were age <18, presence of any immunological disorder or acute/chronic inflammatory disease and history of immunosuppressive or radiation therapy or blood transfusions. Owing to ethical reasons, healthy prostate tissues were not obtained for enzymatic digestion. Prostate tissues used for Inositol monophosphatase 1 immunofluorescence staining were obtained from men during autopsy, which did not show any signs of prostate pathology and served as control samples. Demographic data and blood and prostate tissue samples were acquired in accordance with the published International Health Guidelines outlined in the declaration of Helsinki ‘Ethical principles for medical research involving human subjects’. The study protocol was approved by the Ethics Committee of the Medical Faculty, University of Rijeka, and written informed consent was obtained from each patient and control subject included in the study. Prostate-specific antigen detection.  The concentration of serum PSA of all study subjects was measured photometrically using a Cobas C 601 analyzer (ROCHE Diagnostic, Indianapolis, IN, USA). Isolation of peripheral blood mononuclear cells.  Peripheral blood mononuclear cells were isolated by Lymphoprep (Nycomed Pharma AS, Oslo, Norway) density gradient centrifugation (20 min, 600 g).