34 The three most commonly used BVM devices, Crit-line, Haemoscan

34 The three most commonly used BVM devices, Crit-line, Haemoscan® and Fresenius® BVM, were compared with each other and to laboratory-derived BV changes (based on changes in haemoglobin).32 All three devices yielded values different from the laboratory-derived values and there was also significant variability between the three devices. This possibly reflects the different methods by which the changes in BV are acquired. Modulation of blood volume has been used to assess the different rates of UF on RBV. UF profiles and rates vary from constant, high at onset and isolated pulses. The highest rate of IDH was found in dialysis sessions where UF occurred in pulses or steps.35 Attempts

have been made to measure the changes in RBV over a

series of sessions and store this in the dialysis machine so that UF can be adjusted once the RBV reaches a patient-specific threshold. However, the CH5424802 in vivo this website RBV adjusted for UF varies greatly between dialysis sessions reflecting different UF requirements.36 The more fluid overloaded a patient, the smaller the decrease in RBV per unit of UF volume.36,37 This technology has been expanded to create a preferred UF profile for an individual patient based on stored RBV measurements obtained from these patients. During HD the dialysis machine checks the RBV measurement against the stored profile and adjusts the UF rate and dialysate sodium concentration accordingly. This uses fuzzy logic principles, which aim to derive a definite conclusion from what is often imprecise or ambiguous data. This aims to mimic human decision making allowing a degree of flexibility not possible with mathematical modelling.38 After an initial successful single centre experience39 the biofeedback system technology SPTBN5 has been shown to reduce the incidence of IDH in several randomized trials.19,29,40 A recent study aimed to assess to utility of UF index (UF rates divided by post-dialysis weight), RBV slopes and volume

index (RBV slopes adjusted for UF rate and weight) in determining BV status in 150 difficult patients.41 While these were shown to be possible markers of volume status they did not predict the onset or frequency of IDH. The use of RBV slopes has been shown to be useful in the assessment of IBW in hypertensive HD patients.42 Various BVM technologies are now readily available; however, their utility in IDH remains unclear. BVM devices (especially with the addition of fuzzy logic systems) decrease the incidence of IDH in a at risk population; however, there is limited evidence that BVM can predict IDH in individual patients or that there is a long-term morbidity and mortality benefit, especially in the wider HD population. The technology is undergoing constant refinement, as is the interpretation and analysis of the RBV curves in relation to the other parameters such as weight, UF rate and sodium concentration.


“Early detection and characterisation of a pulmonary focus


“Early detection and characterisation of a pulmonary focus is a major goal in febrile neutropenic patients. Thus, an intensive interdisciplinary co-operation between radiologists and haemato-oncologists on a patient basis, as well as on a department basis is essential to develop a differential diagnosis. The radiologist can contribute much to a differential

diagnosis if information about the patient’s disease, status and medication is made available. On the other hand, the haemato-oncologist needs to understand the opportunities Ipatasertib and limitations of imaging techniques to evaluate better the images and results. This article focuses on pneumonia as the most common focus. First, imaging techniques are summarised shortly. Then, the perspectives for imaging techniques beyond early detection of pulmonary foci – exclusion of pneumonia, monitoring, characterisation of infiltrates and guidance for intervention – are reviewed. “
“Liver transplant recipients

are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to EGFR inhibitor 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1 ± 10.7 vs. 52.5 ± 9.9, P = 0.036), pretransplant MELD score (16.43 ± 8.33 vs. 18.29 ± 9.05), rate of re-transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre-MELD 11.9%, MELD 24.0%, P < 0.05) and Candida infections PIK3C2G (9% vs. 18.9%, P < 0.05) were observed. There was no difference in the incidence of probable or possible aspergillosis. Mortality, length of stay in intensive care or hospital, and duration of mechanical ventilation did not differ between the pre-MELD and MELD era. Regardless the date of transplantation, patients with

fungi-positive samples showed higher mortality rates than patients without. MELD score was analysed as independent predictors for posttransplant IFI. Higher MELD scores predispose to a more problematic postoperative course and are associated with an increase in fungal infections. “
“The genus Malassezia is important in the aetiology of facial seborrhoeic dermatitis (FSD), which is the most common clinical type. The purpose of this study was to analyse the distribution of Malassezia species in the facial lesions of Chinese seborrhoeic dermatitis (SD) patients and healthy individuals. Sixty-four isolates of Malassezia were isolated from FSD patients and 60 isolates from healthy individuals. Sequence analysis of the internal transcribed spacer (ITS) region was used to identify the isolates.

Interventional studies show that after drug cure, allergy may inc

Interventional studies show that after drug cure, allergy may increase at the population level (80,81). Chemotherapy to remove intestinal helminths results, in some studies, in aggravated allergic responsiveness. In a recent double-blinded placebo-controlled interventional trial in an area of Vietnam where hookworm is the most common infection, the anthelmintic-treated group had a significantly increased DNA Synthesis inhibitor incidence of skin allergy sensitivity

to house dust mite or cockroach allergens. This protection correlated with significantly higher levels of baseline IL-10 production to hookworm antigen, with a trend for decreased production of IL-10 after treatment (82). The idea that worm-induced immunomodulation could be used to treat immune dysregulation in the developed world has been gathering support in recent years. A turning point was a clinical trial in the USA, where Trichuris suis, the pig whipworm, was used to treat inflammatory bowel disease. The results of the trial were very encouraging, and the majority

of treated https://www.selleckchem.com/products/Bortezomib.html patients went into remission (83,84). However, the same therapy was ineffective against allergic rhinitis in humans (85). Humans are not a fully permissive host for T. suis, so the infection had to be boosted with larvae every 3 weeks to ensure continual presence of larvae in the gut (86). As a treatment for immune dysregulatory diseases, hookworm may be an attractive prospect – it is virtually asymptomatic in low-level experimental infections (40), it poses no risk of transmission in modern heptaminol sanitary environments and it survives for years within the human host, thus making

continual reinfection unnecessary. British and Australian researchers have used hookworm in seasonal hayfever, Crohn’s disease and coeliac disease, with varying success. The British trials showed that hookworm infection, despite the migratory stage through the lungs, does not exacerbate airway reactivity in allergic individuals; however, no suppression of allergic responses was detected (8,39). No suppression of inflammatory immune responses, as measured by production of IFN-γ or TNF-α, or induction of immunoregulatory mechanisms, as measured by levels of circulating CD4+CD25hiFoxp3+ Tregs or polyclonal CD4+ T-cell production of IL-10, was seen either (8). In contrast, the Australian Crohn’s disease trial led by John Croese showed a strong trend for suppression of Crohn’s disease symptoms after infection (87). However, caveats of this trial include a lack of blinding or a placebo control group, and continued and variable use of immunosuppressants. This trial is currently being extended by Croese and our group, to use hookworm to treat coeliac disease, a gluten-induced enteropathy dependent on a TH1/TH17 response (ms submitted).

21 Historically, groups of patients in early peritoneal dialysis

21 Historically, groups of patients in early peritoneal dialysis (PD) programmes were dialysed incentre using intermittent PD. Because PD effluent from HBsAg positive patients is potentially infectious,22 this regular gathering of patients facilitated transmission of HBV. As a consequence, early infection risks were similar for PD and HD.23 With the development of PD as a predominantly Pritelivir datasheet home therapy, rates of HBV infection in this population have fallen, so that the prevalence of HBV

in PD populations is now heavily influenced by the underlying population prevalence. In countries with very high endemicity of HBV, both PD and HD programmes have similar rates of seropositivity, reflecting HBV acquired before the commencement of dialysis.24,25 Conversely, in countries with low background prevalence, present-day risk PD98059 chemical structure of HBV in PD patients is associated with exposure to blood products and previous time spent on HD. The latest US guidelines for HBV infection control in dialysis units were published in 2001.26,27 Other countries have also produced guidelines.28–30 Underpinning these are established infection-control principles. These include vaccination and screening of HD patients, and segregation of those that are infectious. Safe sharp handling is advised, as is avoidance of multidose

vials for intravenous drugs. Other developments that have contributed to a reduction in infection risk include a widespread move from reusable membranes towards disposable dialysers and the introduction of synthetic erythropoietin with a decrease in blood transfusion. Dialysis unit staff members are at risk of infection through exposure Orotidine 5′-phosphate decarboxylase during the dialysis procedure. Infection with HBV compromises their own health, and risks further staff-to-patient transmission of HBV. Vaccination of all dialysis unit staff is recommended by guidelines, and response rates are >90%.31 Non-responders who are

HBsAg positive should be counselled and assessed accordingly, those who are HBsAg negative should be warned to seek post-exposure prophylaxis in the event of contact with potentially infectious blood. Other steps that can be taken to prevent cross infection with HBV between patients and staff include barrier protection, such as wearing gloves and face shields. Cleaning hands and changing gloves between contacts prevents staff infecting one patient from another. Minimizing staff turnover and allocating dedicated staff to infectious patients is important. Full guidelines relating to management of occupational exposure to HBV, including needlestick injuries is available from the Centers for Disease Control.32 Despite the successes of these measures, HBV outbreaks continue to occur intermittently in HD units. These do not point to inadequacies in infection-control guidelines, but rather to shortcomings in following such recommendations.

VEN and neighbouring neurones (NN) were quantified in layers Va a

VEN and neighbouring neurones (NN) were quantified in layers Va and Vb of the right dorsal ACC in 21 cases of bvFTD, 10 cases of Alzheimer’s disease (AD) and 10 non-demented controls (NDC). A marked VEN reduction was seen in all FTD cases. In the neuropathologically early cases of FTD (n = 13), VEN/10 000 NN was significantly reduced by 53% compared with NDC (P < 0.001) and 41% compared with AD (P = 0.019), whereas

AD patients showed a non-significant 30% reduction of VEN/10 000 NN compared with NDC. VEN reduction was present in all protein pathology subgroups. In conclusion, this study confirms selective sensitivity of VEN in FTD ITF2357 price and suggests that VEN loss is an early event in the neurodegenerative process. “
“S. Orimo, T. Uchihara, T. Kanazawa, Y. Itoh, K. Wakabayashi, A. Kakita and H. Takahashi (2011) Anti-infection Compound high throughput screening Neuropathology and Applied Neurobiology37, 791–802 Unmyelinated axons are more vulnerable to

degeneration than myelinated axons of the cardiac nerve in Parkinson’s disease Aims: We recently demonstrated accumulation of α-synuclein aggregates of the cardiac sympathetic nerve in Parkinson’s disease (PD) and a possible relationship between degeneration of the cardiac sympathetic nerve and α-synuclein aggregates. The aim of this study is to determine whether there is a difference in the degenerative process between unmyelinated and myelinated axons of the cardiac nerve. Methods: We immunohistochemically examined cardiac tissues from four pathologically verified PD patients, nine patients with incidental Lewy body disease (ILBD) and five control subjects, using antibodies against neurofilament, myelin basic protein (MBP) and α-synuclein. First, we counted the number of neurofilament-immunoreactive axons not surrounded by MBP (unmyelinated axons) and those surrounded by MBP (myelinated axons). Next, we counted the Carnitine palmitoyltransferase II number

of unmyelinated and myelinated axons with α-synuclein aggregates. Results: (i) The percentage of unmyelinated axons in PD (77.5 ± 9.14%) was significantly lower compared to that in control subjects (92.2 ± 2.40%). (ii) The ratio of unmyelinated axons with α-synuclein aggregates to total axons with α-synuclein aggregates in ILBD ranged from 94.4 to 100 (98.2 ± 2.18%). Among axons with α-synuclein aggregates, unmyelinated axons were the overwhelming majority, comprising 98.2%. Conclusion: These findings suggest that in PD unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve, because α-synuclein aggregates accumulate much more abundantly in unmyelinated axons. “
“The prognosis of patients with malignant gliomas is still dismal despite maximum treatment. Novel therapeutic alternatives targeting tumorigenic pathways are, therefore, demanded. In murine glioma models, targeting of tumor necrosis factor receptor superfamily (TNFRSF) 9 led to complete tumor eradication.

Production of IL-1β by TLR-mediated macrophages co-cultured with

Production of IL-1β by TLR-mediated macrophages co-cultured with or without purified MLN B cells from SAMP1/Yit and AKR/J mice was evaluated. In addition, interferon-γ (IFN-γ) production in intestinal T cells co-cultured with MLN B cells were also assessed in SAMP1/Yit and AKR/J strains. The production levels of IL-10 VX-809 solubility dmso and TGF-β1 stimulated by LPS and CpG-DNA were significantly

lower in B cells separated from MLNs from the SAMP1/Yit strain. B cells expressing IL-10 and TGF-β1 were mainly located in a population characterized by the cell surface marker CD1d+. Interleukin-1β production by TLR-activated macrophages co-cultured with MLN B cells from SAMP1/Yit mice was significantly higher than that of those from AKR/J mice. Interestingly, IFN-γ production by T cells was noted only when they were co-cultured with SAMP1/Yit but not the AKR/J B cells. These results are the first to show that disorders of regulatory B-cell function under innate immune activation may cause disease pathogenesis in a murine model of Crohn’s disease. Crohn’s disease (CD), an idiopathic inflammatory bowel disease, is characterized by a chronic intestinal immune-mediated disorder.1–4 Previous studies buy Belinostat have

demonstrated that interference with the normal interactions between intestinal mucosal cells and microbial flora is closely associated with the pathogenesis of CD.5–7 Various susceptible genes for CD have been recently identified in several genome-wide association studies,8–12 which further implicates Morin Hydrate their involvement in the development of CD by linking to disorders of the innate immune system. Studies focused on the innate immune system have been crucial for understanding the pathogenesis

of CD. Intestinal innate immunity is maintained by a variety of cells, including macrophages, dendritic cells, and epithelial cells, which express several pattern recognition receptors (PPRs) and can sense luminal pathogen-associated molecular patterns (PAMPs).13–17 Innate immune regulation and disorders of these cells have been widely investigated in numerous studies to elucidate the pathogenesis of CD.5–7 On the other hand, T and B lymphocytes are well recognized as antigen-specific effector immune cells that play a critical role in the adaptive immune response under physiological and pathological conditions.1,2,16–20 Although T- and B-cell-mediated adaptive immune regulation have been evaluated in great detail, the contribution of these lymphocytes in innate immune-related intestinal disorders such as CD has also been recognized. Recent studies have shown that a unique subset of B cells expressing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) plays an essential role in preventing immune responses.21–25 This subset is currently considered to consist of regulatory B cells that designate B cells with immunoregulatory properties.

Exclusion criteria were: the replacement of CNI at any time; acut

Exclusion criteria were: the replacement of CNI at any time; acute deterioration

in allograft functions; and serum creatinine level above 3 mg/dL at 12 months. Banff criteria were used for histopathological classification. Progression was defined as delta ci + ct ≥ 2 (difference between 12th month and baseline). Results:  Mean age of patients and donors were 34 ± 11 and 49 ± 10 years. Twelve patients had delayed graft function (DGF). The maintenance regimen consisted of sirolimus (n = 24) and everolimus (n = 11) with mycophenolate mofetil and steroids. Incidence of acute rejection was 25.7%. At baseline, the incidence of nil and mild fibrosis were 80% and 20%, respectively. At 12 months, 17.1% of patients had moderate, 40% had mild and 42.9% had nil fibrosis. Histological progression from baseline to learn more first year was present in 34% of patients. In multivariate analysis the presence of DGF (P = 0.018) and deceased donor type (P = 0.011) were the most important selleck inhibitor predictors for fibrosis progression. Conclusion:  Progression of graft fibrosis may be seen in one-third of patients under a mTORi-based regimen particularly manifested in deceased donor recipients with subsequent DGF. “
“A clinician may apply the results from randomized controlled trials and population-based cohort studies

to the management of an individual patient to determine whether the patient will achieve more benefit than harm from the intervention. From the data the clinician should determine what are the benefits and harms of the intervention, whether there are any variations in the relative treatment effect, whether the treatment effect varies with different baseline risks of disease in untreated patients, what are the predicted reductions in absolute risk of disease for individuals and whether the benefits outweigh the risks for their patient. If the patient is at a low risk of the outcome, the harms

of therapy may not justify its use to prevent or treat the disease. However, if the patient is at a high risk of developing the outcome, he or she is likely to gain more benefit than harm from the therapy. “
“Aim:  Both vascular calcification and atherosclerosis are highly prevalent in patients with end-stage renal disease (ESRD) and have been associated with increased cardiovascular most morbidity. Because those two phenomena might be only coincidentally related in chronic haemodialysis (HD) patients, in this study, coronary artery calcification (CAC), common carotid artery intima media thickness (CCA-IMT) and thickness of atherosclerotic plaques in the carotid artery were simultaneously measured. Methods:  In a cross-sectional study of 47 HD patients (31 male, mean age 56.8 ± 11.4 years, and 16 female, mean age 56.0 ± 7.5 years) without history of major cardiovascular complications. CCA-IMT and presence and thickness of atherosclerotic plaques were measured with ultrasound and CAC with multidetector computed tomography. Results:  The CAC were present in 70.2% of patients.

T-cell-specific Stat3-deficient mice displayed impaired IL-6-indu

T-cell-specific Stat3-deficient mice displayed impaired IL-6-induced and IL-2-induced T-cell proliferation.[16, 17] Also, Stat3 plays a crucial role in promoting T-cell survival in response to various stimuli.[18] Furthermore, Johnston et al.[19] suggested that the T-cell growth factors IL-2, IL-7 and IL-15 all activate Stat3 and Stat5. Therefore, transcription complexes

that include Stat3 and Stat5 may be of general importance to promote cell proliferation in T cells. Also, Durant et al.[11] examined the CD4+ T cells in the spleen and found that the majority of control (Stat3fl/fl) T cells underwent multiple cell divisions after 5 days. In contrast, fewer than half of Stat3−/− T cells had

divided, Sorafenib order as indicated by CFSE dilution. By 7 days, essentially all of the control T cells had divided, whereas Cytoskeletal Signaling inhibitor 18% of Stat3−/− T cells remained quiescent. In spite of current knowledge about the link between Stat3 and T-cell survival, little is known about how Stat3 regulates T-cell homeostasis in peripheral lymphoid tissues. Using mice with targeted deletion of Stat3 in T cells, we showed that Stat3 maintains the CD4 or CD8 single-positive (SP) thymocytes and naive T-cell pool in the resting condition by promoting the expression of Bcl-2 family genes. This discovery magnifies the significance of Stat3 as a master regulator of homeostatic signals for the maintenance and functional adjustment of the naive T-cell population. Mice homozygous for the loxP-flanked (floxed) Stat3 gene (Stat3fl/fl) were a kind gift from Dr S. Akira.

Mice carrying a Cre transgene under the control of the distal Lck promoter (Lck-CRE+/+)were purchased from The Jackson Laboratory (Bar Harbor, ME). Mice with a Stat3 deletion in T cells were generated by crossing mice with the floxed Cyclic nucleotide phosphodiesterase Stat3 allele with mice expressing Cre under the control of the Lck promoter.[17] Genomic DNA was isolated from tail tips using a NucleoSpin genomic DNA purification kit (Macherey-Nagel GmbH & Co., Duren, North Rhine-Westphalia, Germany). Genotyping was performed with the primers CCTGAAGACCAAGTTCATCTGTGTGAC and CACACAAGCCATCAAACTCTGGTCTCC, which are specific for exons 22 and 23 of Stat3, respectively.[20] Mice carrying Cre were identified by genotyping with the primers GCGGTCTGGCAGTAAAAACTATC and GTGAAACAGATT-GCTGTCACTT, which are specific for the Cre transgene, according to the manufacturer’s instructions. All animals were maintained under specific pathogen-free conditions and all experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the College of Medicine, Seoul National University.

The differences of plasma cytokine levels were examined using a n

The differences of plasma cytokine levels were examined using a non-parametric Kruskal–Wallis test and the Mann–Whitney U-test. Correlations were assessed Selleck R428 using Spearman’s rank correlation test. Statistical analyses of time–courses and levels of phosphorylation for STAT-3 and STAT-1 between groups were performed using two-way anova. In all tests, statistical significance

was defined as a P-value < 0·05. To determine if IL-10R1 was expressed aberrantly in SLE patients, we examined the IL-10R1 expression on PBMC subsets from SLE patients by flow cytometry. Figure 1a shows the representative flow cytometric histograms of IL-10R1 expression on the different leucocyte subsets. We found that the expression intensities varied among peripheral CD4+ T lymphocytes, CD8+ T lymphocytes, CD14+ monocytes and CD19+ B lymphocytes. The highest levels of IL-10R1 were consistently on monocytes, the next highest levels were on CD8+ cells and CD4+ cells, and the lowest levels were on CD19+ cells. The MFIs of IL-10R1 on CD14, CD8, CD4 and CD19 cells from healthy control

subjects were 34·4 ± 8·3, 19·1 ± 3·8, 15·7 ± 3·9 and 10·0 ± 3·4, respectively. No significant differences in IL-10R1 intensity on total leucocytes or leucocyte subsets were observed between 28 SLE patients and 14 healthy controls. In addition, no differences were observed among eight newly diagnosed SLE patients, 20 treated patients and 14 Selumetinib mouse healthy controls, or between any two groups. These results indicated P-type ATPase that IL-10R1 was not commonly involved in SLE pathogenesis. As SLE patients developed various clinical manifestations of their disease, we looked for the association of

IL-10R1 abnormalities with specified clinical subtypes and found that the expression intensity of IL-10R1 was lower in PBMCs from patients with LN. As shown in Fig. 1b, the IL-10R1 expression intensity on CD4+ cells from LN patients was significantly lower compared to cells from healthy controls and SLE patients without LN (non-LN patients); the MFIs were 12·8 ± 2·9 versus 15·9 ± 2·4 and 21·7 ± 4·2, P < 0·01. In addition, we observed that the IL-10R1 expression intensity on CD8+ cells from LN patients was significantly lower than on CD8+ cells from non-LN patients (MFIs were 16·9 ± 3·2 versus 21·8 ± 4·1, P < 0·01), but only slightly (not significantly) lower than on cells from controls. Although we observed that non-LN patients also expressed slightly higher levels of IL-10R1 on CD14+ and CD19+ cell subsets, no significant differences were observed among controls, LN and non-LN patients, or between any two groups. We assessed the correlation between IL-10R1 expression levels and SLEDAI scores using Spearman’s rank correlation test. As shown in Fig. 2a, a strong negative correlation was observed between the expression intensity of IL-10R1 on CD4+ cells and the SLEDAI scores.

C57BL/6 mice (2 months old) were i n infected with 5 HAU of infl

C57BL/6 mice (2 months old) were i.n. infected with 5 HAU of influenza virus. After 3 days, lung mononuclear cells were isolated from infected mice or uninfected mice, and then the cell suspensions were layered on a Histopaque-1083 gradient (Sigma-Aldrich), and centrifuge at 400 × g for 30 min at room temperature. Subsequently NK cells were purified using a negative selection mouse NK cell enrichment kit (StemCell Technologies), and labeled by CellTrace™

Violet (Invitrogen Corporation). As described previously [52, 53], 2 × 106 NK cells in 0.25 mL PBS were injected i.v. into recipient mice via the tail vein. On the same this website day, the mice were i.n. infected with 5 HAU of influenza A/PR8 virus. After infection, NK cells from lung and spleen were analyzed by flow cytometry 15 h later. The survival rate and body weight of

infected mice were monitored daily. Two months selleck screening library old C57BL/6 mice were i.n. infected with 5 HAU of influenza virus or normal egg allantoic fluid on day 0. At days 2, 4, and 6 after infection, mice were euthanized and lungs were isolated and fixed in 10% buffered formalin, then embedded in paraffin and sectioned. Specimens were stained with H&E and examined using a Zeiss Axio Imager M1 microscope equipped with an AxioCam HRc camera under control of AxioVision 4 software (Carl Zeiss Canada Ltd.). GraphPad Prism 4.00 (GraphPad Software, Inc., San Diego, CA, USA) was used for all analyses. Differences among experimental groups were assessed by one-way ANOVA followed by Tukey multiple comparison test. Unpaired t-test (two-tailed) was used to compare pairs of groups. Survival curves were assessed by survival analysis in Prism. Values were reported as the mean ± SEM. This work was supported by operating grants from the Canadian Institutes for Health Research (to K.P.K.). We thank Suellen Lamb, Dr. L. Tyrrell Laboratory, University of Alberta for making histologic sections

and performing hematoxylin and eosin staining. We thank Donger Gong for her technical support. The authors declare no financial or commercial conflict of interest. “
“The description of highly MRIP exposed individuals who remain seronegative (HESN) despite repeated exposure to human immunodeficiency virus (HIV)-1 has heightened interest in identifying potential mechanisms of HIV-1 resistance. HIV-specific humoral and T cell-mediated responses have been identified routinely in HESN subjects, although it remains unknown if these responses are a definitive cause of protection or merely a marker for exposure. Approximately half of HESN lack any detectible HIV-specific adaptive immune responses, suggesting that other mechanisms of protection from HIV-1 infection also probably exist.