The reproducibility of LTH is strongly dependent on the way of expressing data and the technique used to record skin blood flux. When using single-point LDF, we found the inter-day reproducibility of both peak and plateau expressed as raw CVC to be acceptable for finger pad measurements (CV were 17% and 25%, respectively), but not for measurements

on the forearm (CV were 57% and 40%) [114]. Normalizing baseline skin temperature to 33°C before heating did not improve the inter-day reproducibility of LTH on the Fulvestrant cost forearm, whatever the way of expressing data [117]. Other groups have found better reproducibility of LTH on the forearm by using integrating probes (which process an integrated signal taken as the average flow value from seven or eight different scattering volumes). Agarwal et al. found CV ranging from 9% to 38%, depending on the method of data expression [2]; however, the heating conditions were different from ours; the heating rate was 10-fold lower and the maximum temperature was 41°C. Moreover, Agarwal et al. used local anesthesia to avoid axon reflex vasodilation, thus providing data only for the plateau [2]. Tew et al., using a similar protocol and form of data expression to ours, showed better reproducibility of LTH on the DMXAA concentration forearm expressed as raw CVC, %CVCmax or %CVCBL, both for the initial peak (CV were 19%, 11%

and 32%, respectively) and for the plateau (CV were 19%, 4% and 30%, respectively) [130]. The inter-day reproducibility of LTH on the forearm when using full-field techniques such as LDI was good for the plateau (CV was 17% when expressed as raw CVC) [117]. However, LDI was not as accurate when used to assess the LTH peak on the Resminostat forearm,

probably because of its slow kinetics over wide areas (CV for peak was 39% when expressed as raw CVC). The good inter-site reproducibility of peak CVC simultaneously assessed at two sites on the same forearm strengthens this hypothesis [117]. As such, lower resolution over smaller areas would probably increase peak reproducibility using LDI, but to the detriment of the main advantage of LDI, i.e., recording flux over wide areas. We found that the recently marketed high frame rate LSCI offers excellent inter-day reproducibility of the LTH peak and plateau on the forearm (see below). These results suggest that lowering inter-site variability (by using integrating LDF probes or full-field techniques) could be decisive in improving the inter-day reproducibility of LTH on the forearm (Table 1). Although many heating protocols have been proposed, local warming to 42–43°C is usually sufficient to induce maximal vasodilation [71]. In our experience, heating to 44°C is well tolerated in healthy subjects, but may lead to pain or a burning sensation in patients with abnormal microvascular function (e.g., systemic sclerosis).

Chapters 3 (Forensic Aspects of Adult General Neuropathology) and 4 (General Forensic Neuropathology of Infants and Children) offer a surprisingly comprehensive overview of the natural disease processes which may be encountered in a forensic setting. The whole range of pathological processes, from vascular disease and neoplasia to central nervous system malformations and infectious diseases (with many more besides), Sirolimus are summarized elegantly and succinctly in just over 260 pages. Chapter 5 (Forensic Aspects of Intracranial Equilibria) considers the systems and physiological principles that preserve the internal milieu

of the central nervous system and what happens when these systems fail. Chapter 6 (Physical Injury to the Nervous System) is a comprehensive account of the neuropathology of trauma. Reflecting the multidisciplinary authorship of the book, this chapter starts with an introduction to the principles of biomechanics – an important overview of the basic sciences which determine the pathophysiological response of CSF-1R inhibitor the central nervous system to injury. Chapter 7 (Child Abuse: Neuropathology Perspectives)

gives a thoughtful review of one of the most controversial areas in neuropathology. This includes a useful summary of the forensic issues surrounding subdural haematoma in the context of child abuse and the various controversies surrounding the ‘shaken baby syndrome’. Chapter 8 considers gunshot and penetrating wounds of the nervous system, while the final chapter (Forensic Aspects of Complex Neural Functions) looks at disorders of higher-order functions of the nervous system (epilepsy, dementia, cognitive–perceptual difficulties, behavioural illness, and

disorders of consciousness and coma) and their forensic implications. It is an authoritative and comprehensive text which covers the relevant neuropathology in considerable detail. The details of the first two chapters are mostly fantofarone applicable to those working in the USA. However, the broad principles will stand anyone who finds themselves acting as an expert witness in good stead. The descriptions of the macroscopic and histological appearances are clear and are supplemented by uniformly high-quality colour images. Each chapter is extensively referenced. The detailed overview of general adult and paediatric neuropathology as applied to the forensic setting is a bonus for both the general neuropathologist and forensic neuropathologist alike. I found the inclusion of the principles of biomechanics to be a distinct bonus. I would strongly recommend that readers not be deterred by the prospect of revisiting some basic physics and mathematics. The occasional mathematical equations that appear in the overview of biomechanics are clearly explained by example in the text.

ALOX5AP itself lacks enzymatic activity and instead serves to enhance 5-lipoxygenase (LO) activity [9]. In the first step of the 5-LO pathway, 5-LO, in co-operation with ALOX5AP, converts arachidonic acid to leukotriene (LT) A4 (LTA4). Subsequently, LTA4 can be converted to LTB4 by LTA4 hydrolase and/or converted to LTC4 by LTC4 synthase; LTC4 is then cleaved into LTD4 and LTE4 [10]. The products of the

5-LO pathway, including LTC4, LTD4, LTE4 and LTB4, are known to play an important roles in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis [11]. Many studies have analysed the genes in the 5-LO pathway for possible associations with asthma-susceptibility. For example, Choi et al.

[12] found that the ALOX5-[G-C-G-A] haplotype influences the development Bortezomib of aspirin-intolerant asthma in a Korean population. The same study also showed that leukotrienes may play a role in the pathophysiology of asthma in a Korean population. Moreover, it has been reported that patients with asthma express ALOX5AP at higher levels than the general population [13]. Another study has shown that ALOX5AP promotes asthma either on its own and/or via its interactions with genes in the find more leukotriene pathway [14]. In addition, ALOX5AP has been reported to play a critical role in the pathogenesis of various cardiovascular diseases [15, 16]. Therefore, inhibitors of ALOX5AP are likely to be clinical beneficial in allergic asthma and various cardiovascular diseases [17]. However, although it has been proposed that ALOX5AP may play a potentially causative role in asthma, its relationship with lung Rebamipide function in a general population has not yet been examined [18]. In this study, the influence of genetic variation in the ALOX5AP gene on the lung functions of a healthy and general population was evaluated. Subjects.  The data used in this study were obtained from the Korea Association Resource (KARE) project in the Korean

Genome Epidemiology Study (KoGES), which began in 2001, was conducted by the Korea National Institute of Health (KNIH) [19]. The KoGES study was a cross-sectional analysis of 5018 and 5020 subjects from urban (Ansan) and rural (Ansung) communities in Korea, respectively. The ages of the participants ranged from 40 to 69 years. After a quality control process had been implemented, 8842 subjects in total were selected. General characteristics (age, sex, area, height, etc.), smoking status, medical history and current medications were collected from participants by questionnaires and the assessments were managed by trained interviewer. The participants have been examined every 2 years and 6-year follow-up study was currently completed. The procedures were conducted according to institutional guidelines and approved by an institutional review committee.

The indicator strains were representative strains of URTIs including AOM pathogens: S. pyogenes group (S. pyogenes 2812A serotype M18, S. pyogenes Spy35370 serotype M1 and F222 serotype M2), Haemophilus influenzae 3ATF, S. aureus 10F, Escherichia coli 12I, Pseudomonas aeruginosa 115, S. salivarius ATCC13419, and B. catarrhalis 120, S. pneumoniae group Ibrutinib solubility dmso including three not-typed clinical isolates of

S. pneumoniae (11ATN, 22ATN and 148) and three S. pneumoniae serotype 19A (BT S. pneumoniae; CR S. pneumoniae; GC S. pneumoniae), which are responsible for cases of pediatric meningitis in Sicily, Italy. All S. pneumoniae used were resistance to erythromycin, clindamycin, and susceptibility to penicillin and ampicillin. All strains used as indicator strains in the deferred antagonism test were clinical strains except S. salivarius ATCC13419. The BLIS production was also tested using a deferred antagonism test on Trypticase Soy Yeast Extract Calcium agar (Trypticase Soy Broth; Oxoid) + 2% Yeast extract (Oxoid) + 1.5 agar (Oxoid) + 0.1% CaCO3. Total bacterial DNA was extracted in agarose plugs as described before (Santagati et al., 2009). After

digestion with the SacII enzyme (TaKaRa BIO), macro-restriction fragments were resolved in a 1% agarose gel using 0.5× tris-borate-ethylene Y-27632 mw diamine tetra-acetic acid buffer (BioRad) at 14 °C. The CHEF DRPFGE (BioRad) system was used, and switch and run times were 1″ to 15″ for 20 h, with a voltage gradient of 6 V cm−2. The macrorestriction fragments were visualized by a blue-light trans-illuminator (Safe Imager Invitrogen) after staining with 1× SYBR Green (SYBR Safe DNA gel staining Invitrogen) in TBE0.5×. The macrorestriction fragments were transferred from the gel to a nylon Hybond N+ membrane, (Amersham International UK) in a downward direction using a Vacuum blotter 785 (BioRad) and denaturing solutions (NaOH 0.5 M/NaCl 1.5 M). DNA fragments were immobilized by UV radiation (Ultraviolet Crosslinker, Amersham). The hybridization assays

with sagA, smeZ-2, speB, speC, speJ, speG, prtF, and sof probes were performed using the ‘ECL Direct Nucleic Acid Labeling and Detection System’ (RPN 3000 Amersham), following the protocol provided with the kit. The probes were obtained by PCR from the S. pyogenes SF370 and S. pyogenes 2812A genome and purified with Cyclic nucleotide phosphodiesterase the QIAquick PCR purification kit (Qiagen) using the primers described in Table 1. For all bacteriocin producer strains, the presence of plasmids was investigated by Plasmid Midi Kit (Qiagen) according to the manufacturer’s instructions, preceded by one lysis step with 20 mg mL−1 lysozyme solution and incubated at 37 °C for 30 min. In addition, the chromosomal versus plasmid localization was evaluated by the I-CeuI method, as described previously (Liu et al., 1993). Streptococcus salivarius K12 was used as positive control. Total genomic DNA was digested overnight with I-CeuI and was subjected to pulsed-field gel electrophoresis (PFGE) as previously described.

One mechanism by which irradiation is thought to enhance HSC engraftment is by stimulating the release of factors that improve the homing and survival of stem cells such as stem cell factor (SCF) [63] and SDF-1 [68]. However, total body irradiation has a number of negative consequences, including stunting growth and impairing neuronal function [19, 69]. Recent work from our laboratory and others have demonstrated that both adult and newborn selleck compound NSG mice will support human

HSC engraftment in the absence of irradiation [69, 70]. Moreover, the transgenic expression of human SCF improves human HSC engraftment significantly in non-irradiated NSG mice [69]. In this study we show that irradiation is not essential for the human immune system development in NSG–BLT mice, although irradiation increases levels of human chimerism. One significant difference for non-irradiated NSG–BLT Dorsomorphin mice

was the lower level of human IgM detected in the serum compared to NSG–BLT mice that were preconditioned with irradiation. The reduced levels of IgM may be attributed to the slightly reduced levels of human B cells in the spleens of non-irradiated NSG–BLT mice. To allow for complete analysis of the engraftment data, we have also presented the human cell chimerism levels shown in Figs 1-3 (human CD45+, human CD3+ T cells and human CD20+ B cells) for each unique set of human fetal tissues (Supporting information, Fig. S9). The NSG–BLT mouse has sustained high levels

of human cell chimerism and T cells in the peripheral lymphoid tissues. However, many NSG–BLT mice succumb ultimately to a GVHD-like syndrome [54] which has also been reported for BLT mice generated on the NOD-scid background [26]. The development of the delayed GVHD-like syndrome in NSG–BLT mice correlated with the transition of human T cells to an activated phenotype and increased G protein-coupled receptor kinase levels of human IgM and IgG in the serum. This late, spontaneous activation of the human immune systems suggests that a peripheral tolerance mechanism is abrogated as NSG–BLT mice age, and this loss of tolerance allows the human immune system to respond to the murine host. T cells are a primary effector population mediating tissue damage during classic GVHD [71], and the high levels of human T cell chimerism in the NSG–BLT mice suggest that these cells are key mediators of the disease pathology. Our data show that the development of GVHD in NSG–BLT mice does not require the expression of murine MHC classes I or II, indicating that either human CD4 or CD8 T cells or both probably mediate GVHD, or that murine MHC classes I or II are not necessary for disease development. We are initiating studies to evaluate further the mechanism mediating GVHD in NSG–BLT mice by generating NSG mice that lack both murine classes I and II and by the depletion of human T cell subsets at precise time-points.

On the Schäfer nomogram, six of nine Group 1 cases had obstructions less than IV and normal or weak detrusor contractility. For Group 2, six of eight cases had obstructions more than IV and normal or strong detrusor contractility. Conclusion: Patients with higher levels of alpha-1D AR mRNA were distinct from those with higher alpha-1A AR mRNA levels with regard to obstruction and detrusor activity. The results suggest that the Schäfer

nomogram might be useful in determining which alpha-1 AR antagonists are better for BPO Luminespib mw patients suffering from storage symptoms. “
“Objectives:α1-blockers have commonly been used as first-line medical therapy for symptomatic benign prostatic hyperplasia (BPH). Recently, a highly selective α1A-adrenoceptor antagonist, silodosin, was developed in Japan. We examined the efficacy and safety of conversion from conventional α1-blockers to silodosin in men with BPH. Methods: Conversion to

silodosin was proposed to consecutive patients on conventional α1-blockers for symptomatic BPH for at least 6 months. The effects of conversion were examined by the International Prostate Symptom Score, quality of life index, overactive bladder symptom score, peak flow rate, residual urine volume, and adverse STI571 ic50 events at 12 weeks. The efficacy of silodosin was also evaluated by patients’ impression. Results: Eighty-one men underwent conversion, for the most part because of dissatisfaction with the efficacy of their current treatment in improving nocturia or weak stream. The International Prostate Symptom Score total score significantly improved from 12.7 ± 5.9 at baseline to 10.6 ± 5.4 at 4 weeks (P < 0.001) and 10.9 ± 5.8 at 12 weeks (P < 0.01). The progress was mostly due

to improvement in voiding symptoms, although reduction of storage symptoms was also significant. The quality of life index also significantly Carbohydrate decreased with conversion to silodosin. Efficacy as judged by patients’ impression was 76% (37/49) at 12 weeks of treatment. None of the overactive bladder symptom score, peak flow rate, and residual urine volume exhibited significant change. No serious adverse events were observed during the study period. Conclusion: Conversion to silodosin may be beneficial in men who are dissatisfied with conventional α1-blockers for BPH, and be particularly useful in improving voiding symptoms. “
“Objectives: To estimate correlations among lower urinary tract symptoms (LUTS), bother, and quality of life (QOL) and assess fluctuations in these parameters after α1-blocker administration in patients with benign prostatic hyperplasia (BPH). Methods: Untreated BPH patients with international prostate symptom scores (IPSS) ≥ 8 and IPSS-QOL scores ≥ 2 were administered tamsulosin at 0.2 mg/day for 4 weeks in a prospective multicenter study. We subsequently estimated the IPSS, bother score for each IPSS item, BPH impact index (BII), and IPSS-QOL score before and 4 weeks after tamsulosin administration.

The high levels of intracellular TRAF2 in TNFR2−/− cells then promote the pro-survival function of TNFR1, which is mediated by the activation of the canonical NF-κB pathway, which involves phosphorylation of the IκBα inhibitory subunit and NF-κB activation, as evidenced by an increase in the binding of the p65 NF-kB subunit to the NF-κB consensus site. Since the pro-survival function of TNFR1 in TNFR2−/−

CD8+ T cells, which express WT levels of TNFR1, is blocked by neutralizing anti-TNF-α antibodies, this observation indicates that TNFR1 functions as a pro-survival receptor in TNFR2−/− CD8+ T cells. These studies also illustrate the importance of cross talk between TNFR1 and TNFR2 in determining survival versus death of activated T cells. They selleck screening library also suggest novel mechanisms for regulating T-cell responses by regulating the activity of TNFR1 and TNFR2 at various stages of T-cell Alvelestat in vivo activation. For instance, specific inhibition of TNFR2 function at later stages of T-cell activation may prolong the survival of activated T cells by promoting the pro-survival function of TNFR1. We noted that the addition of a neutralizing TNF-α

antibody reduced the proliferative response of anti-CD3-stimulated WT CD8+ to almost basal level, a level that was significantly lower than that observed for cultures of TNFR2−/− CD8+ T cells activated under the same conditions (Fig. 5B). It is unlikely that the amount of neutralizing anti-TNF-α antibody in cultures of TNFR2−/− CD8+ T cells activated Rho under these conditions was insufficient for neutralizing

TNF-α since anti-CD3-activated WT and TNFR2−/− CD8+ T cells produced similar amounts of TNF-α. We have previously shown that anti-CD3-activated TNFR2−/− CD8+ T cells produced very little IL-2 compared with similarly activated WT CD8+ T cells 7. IL-2 has been shown to sensitize anti-CD3-activated CD8+ T cells to AICD 22 via a Fas/Fas ligand-dependent mechanism 23, 24. Interestingly, anti-CD3-activated TNFR2−/− CD8+ T cells are also highly resistant to Fas/Fas ligand-induced cell death 9. It remains to be determined whether TNFR2 regulates Fas/FasL-induced cell death in CD8+ T cells by a TRAF2-dependent or independent mechanism. Nevertheless, regardless of the mechanism by which TNFR2 regulates Fas/FasL-induced cell death, it is likely that the lower proliferative response observed for WT CD8+ T cells as a result of TNF-α neutralization is due to higher susceptibility to Fas/Fas ligand-induced cell death as a result of higher production of IL-2 in these cultures. We have previously reported that the resistance of activated TNFR2−/− CD8+ T cells to AICD correlates with high expression levels of pro-survival molecules such as Bcl-2, surviving and CD127 10. In a more recent study, we showed that the resistance of activated TNFR2−/− CD8+ T cells to AICD correlated with more effective protection against the growth of syngeneic tumor cells.

The effects had never been studied yet on a lung model for large mammals. Our data showed dose-dependent effects of CsA on gas exchanges, but also on pulmonary hemodynamics, and possibly an aggravation of the IRI due to high doses of CsA. These results constitute an important step toward the use of CsA on humans to reduce lung IRI and consequently, primary graft dysfunction. Within a few years, the EVLP technique has become a reference for the evaluation of lung grafts. Its interest has been demonstrated PLX4032 purchase on animal

lung preparations, especially on pig [43] and human lungs [12]. This technique can be seen as bench test for lung function, allowing for the assessment of new therapies suppose to limit IRI. Gas exchange capacities and total pulmonary arterial resistance are more commonly studied physiopathological parameters. We also measured other hemodynamics (Pcap,

longitudinal pulmonary resistance) and markers (AFC, RAGE, cytokines, lung permeability) that have showed their pertinence in the evaluation of lung IRI [5, 7]. It has been hypothesized that IRI is mostly related to mitochondrial death as a consequence of MPTP opening. Located in the inner mitochondrial membrane, the MPTP remains unremarkable under normal physiological conditions. Stress can lead to its opening, resulting in the swelling of the matrix due to osmotic forces. It then induces further failure of the mitochondrial outer membrane and the release of the cytosol pro-apoptotic factors [19]. The inhibition of PXD101 clinical trial the opening of MPTP is thought to be the main pathway for CsA action. Several in vitro and in vivo animal models showed CsA interests in pre and post-conditioning for the

prevention of IRI on different organs such as heart, kidney, and liver [19, 20, 45, 50]. In humans, CsA administered just before coronary reperfusion (post-conditioning) has been proven to be an efficient way to reduce the size of myocardial infarction [33]. However, few studies have been published on CsA effects on lung IRI. In vitro studies on post hypoxia-reoxygenation injuries showed that alveolar macrophages pretreated by CsA secreted less chemokines than Tideglusib controls [30]. Moreover, endothelial cells incubated with CsA selectively reduced pro-inflammatory mediator secretion of NFκB and EGR-1 [15]. Nevertheless, some of the pathways involved in IRI can be activated by CsA, such as the metalloproteinase and the TLR [1, 28, 41]. Such insights can explain the increased levels of pro-inflammatory cytokines we measured in our experiments with high doses of CsA (30 μM). In an in vivo ischemic lung model, Krishnadasan et al. showed that rats pre-conditioned with CsA displayed less tissue myeloperoxidase content, leukocyte accumulation, and vascular permeability [25].

Since lipopolysaccharide-binding protein (LBP) is the first protein to encounter lipopolysaccharide, we assessed the relationship among, microbial translocation marker, LBP, proinflammatory cytokines and monocyte activation in hemodialysis patients.

Methods: A total of 120 patients undergoing hemodialysis were studied, and correlates with markers of inflammation. Levels of LBP, markers of inflammation, as well as markers of monocyte activation and traditional risk factors for dialysis patients were assessed. Results: Serum LBP concentration was significantly increased in all HD patients in compared with 40 healthy individuals (20.7 ± 8.1 mg/mL vs. 7.6 ± 2.5(mg/mL, respectively; p < 0.001). In HD patients, a significant positive correlation was found between Navitoclax in vitro LBP levels and CRP, IL-6, sCD14 and fasting blood glucose levels. Incremental BMI were observed with increasing LBP quartiles There is also a linear correlation between the proportion of proinflammatory moncoytes (CD16+ monocytes) and levels of LBP (r = 0.16,

p < 0.05). Multivariate regression analyses showed that IL-6 level was the strongest correlate of LBP level (r = 0.28; P = 0.003), followed by hsCRP level (r = 0.27; P = 0.004), and sCD14 (r = 0.16; P < 0.05). Conclusion: Increased LBP level is related positively to markers of inflammation and proportion of proinflammatory monocytes. Understanding the underlying reasons behind Everolimus these associations may have clinical relevance given the adverse clinical outcome of chronic inflammation described for the dialysis patients. YAMAMOTO

SUGURU1, OMORI KENTARO2, MATSUO KOJI1, TAKAHASHI YOSHIMITSU1, KAWAMURA KAZUKO1, MARUYAMA HIROKI1, KAZAMA JUNICHIRO J.1, NARITA ICHIEI1 1Niigata University Graduate School of Medical and Dental Sciences; 2Omori ROS1 clinic Introduction: An accumulation of protein-bound uremic toxins, such as indoxyl sulfate and p-crecyl sulfate, increases the risk of cardiovascular disease with direct/indirect interaction in CKD patients undergoing dialysis treatment. Oral activated charcoal adsorbent, AST-120, has been shown to decrease serum indoxyl sulfate in non-dialysis CKD patients. The aim of this study is to examine whether AST-120 decreases protein-bound uremic toxins in maintenance hemodialysis patients. Methods: Twenty maintenance hemodialysis patients were individually randomized in a crossover design between treatment with 6 g/day of AST-120 and non-treatment for 4-week periods. Ten participants followed the AST-120 treatment first for 2 weeks and then switched to non-treatment for another 2 weeks; the other 10 subjects followed the same treatment in reverse order. Serum level of indoxyl sulfate and p-crecyl sulfate at pre/post dialysis session before and after the AST-120 treatment was measured by mass spectrometry. Data were presented as means ± standard deviation. Paired t-test was used for the statistical analysis.

We also compared the RTL of sorted CD4+CD28null to that of CD4+CD28+ (purity > 95%) T cells and found that the CD4+CD28null T cells had significantly shorter telomeres (P < 0·01) compared to the CD4+CD28+ T cells (Fig. 3d). CMV affected the

CD8+ T cell LDE225 compartment more profoundly than the CD4+ T cell compartment. CMV-seropositive ESRD patients had a significantly (P < 0·05) lower CD8 naive/memory ratio (Fig. 4a), due to a higher number of memory CD8+ T cells consisting of a large population of terminally differentiated CD8+ EMRA T cells (absolute numbers: CMV-seronegative: 0·03 × 106, CMV-seropositive: 0·12 × 106, P < 0·05). This was reflected by the significantly lower CD28+/CD28− PS-341 clinical trial (Fig. 4b) (P < 0·001) and CD57−/CD57+ ratio (Fig. 4c) [P < 0·01 (young) and P < 0·001 (elderly), respectively]. Similarly, as observed for the CD4+ T cell compartment, a significantly higher proportion of CD8+ T cells had a senescent phenotype in CMV-seropositive ESRD patients when compared to their age-matched CMV-seronegative counterparts (young CMV-seropositive: 50·56% ± 3·77 versus young CMV-seronegative: 15·56% ± 4·99, P < 0·01 and old CMV-seropositive: 47·15% ± 4·09 versus old CMV-seronegative: 27·94% ± 5·16, P < 0·05). Also, for the CD8+ T cells we determined the RTL in CD28null and CD28+ T cell-sorted populations. The CD8+CD28null T cells had significantly shorter (P < 0·01) telomeres

than the CD8+CD28+ T cells (Fig. 4d). In an attempt to explain the additional telomere attrition induced by CMV, we determined whether CMV infection induced an increase in the proliferation of CD4+ as well as CD8+ T cells by determining the percentage of Ki-67+ T cells (i.e. the percentage of T cells actually dividing). No significant differences were observed in the percentage of Ki-67+ CD4+ or CD8+ T cells (CD4+Ki-67+ T cells; CMV-seronegative: 2·09% ± 0·68 PRKD3 CMV-seropositive: 1·33% ± 0·52 and CD8+Ki-67+ T cells; CMV-seronegative: 1·99% ± 0·60 CMV-seropositive: 1·34% ± 0·25). The results of this study show

that CMV-seropositivity is associated with more differentiated memory CD4+ and CD8+ T cell compartments. These highly differentiated T cells show loss of CD28 expression, increased expression of CD57 and shorter telomeres. CMV did not affect the thymic output of new naive T cells, and therefore CMV-seropositivity impacts only partly upon the ESRD-related immunological ageing of the T cell system. In a previous study [10], we observed that the characteristics of the peripheral T cell system of ESRD patients are very similar to healthy individuals with a chronological age that is, on average, 20–30 years older. One of the salient findings in ESRD patients and elderly healthy individuals was a decreased number of circulating naive T cells [10]. In humans, the thymus is the single organ involved in naive T cell generation.