Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of primary angiitis of the central nervous system in childhood with mycophenolate mofetil.

OBJECTIVE To assess the use of mycophenolate mofetil (MMF) in the treatment of refractory primary angiitis of the CNS in childhood (cPACNS). METHODS A retrospective chart review was performed in patients with cPACNS who were treated with MMF following failure of a combination of corticosteroids and another immunosuppressant. RESULTS Three patients from two centres were included in this study. The age of onset of disease was 5, 6 and 9 years. All the patients improved when treated with MMF, such that the dose of corticosteroids could be weaned or stopped. CONCLUSIONS MMF should be considered for maintenance treatment in the management of patients with cPACNS refractory to the combination of corticosteroids and first-line immunosuppressive agents.
Inhibition of phosphoantigen‐mediated γδ T‐cell proliferation by CD4+ CD25+ FoxP3+ regulatory T cells

Tumour growth promotes the expansion of CD4+ CD25+ FoxP3+ regulatory T cells (Tregs) which suppress various arms of immune responses and might therefore contribute to tumour immunosurveillance. In this study, we found an inverse correlation between circulating Treg frequencies and phosphoantigen‐induced γδ T‐cell proliferation in cancer patients, which prompted us to address the role of Tregs in controlling the γδ T‐cell arm of innate immune responses. In vitro, human Treg–peripheral blood mononuclear cell (PBMC) co‐cultures strongly inhibited phosphoantigen‐induced proliferation of γδ T cells and depletion of Tregs restored the impaired phosphoantigen‐induced γδ T‐cell proliferation of cancer patients. Tregs did not suppress other effector functions of γδ T cells such as cytokine production or cytotoxicity. Our experiments indicate that Tregs do not mediate their suppressive activity via a cell–cell contact‐dependent mechanism, but rather secrete a soluble non‐proteinaceous factor, which is independent of known soluble factors interacting with amino acid depletion (e.g. arginase‐diminished arginine and indolamine 2,3‐dioxygenase‐diminished tryptophan) or nitric oxide (NO) production. However, the proliferative activity of αβ T cells was not affected by this cell–cell contact‐independent suppressive activity induced by Tregs. In conclusion, these findings indicate a potential new mechanism by which Tregs can specifically suppress γδ T cells and highlight the strategy of combining Treg inhibition with subsequent γδ T‐cell activation to enhance γδ T cell‐mediated immunotherapy.
Staphylococcus aureus resistente a meticilina adquirido en la comunidad aislados en tres hospitales de Lima-Perú. Methicillin resistant Staphylococcus aureus isolates acquired in the community in three hospitals in Lima, Peru.

PALABRAS CLAVE: Staphylococcus aureus, resistente, meticilina, comunidad. SUMMARY Background : Staphylococcus aureus is an important pathogen involved in a series of infections and toxin mediated syndromes, has many virulence factors and its impact increases its resistance to antimicrobial agents. Objectives: To determine the frequency of community acquired methicillin resistant Staphylococcus aureus among hospitals in Lima -Peru. Material and Methods: We performed a prospective multicenter study. The resistance to methicillin was determined by the Oxacillin Agar Screen method. The origin of the strain was determined using CDC criteria,
The decrease of regulatory T cells correlates with excessive activation and apoptosis of CD8+ T cells in HIV‐1‐infected typical progressors, but not in long‐term non‐progressors

Persistent HIV infection results in a decrease in absolute counts of CD4+ CD25+ regulatory T cells (Treg). To investigate the role of decreased Treg counts in the regulation of excessive activation and apoptosis of CD8+ T cells in human immunodeficiency virus (HIV)‐1 infection, we characterized Treg in 83 HIV‐1‐infected individuals, including 19 long‐term non‐progressors (LTNPs) and 51 typical progressors (TPs) who were treatment‐naïve, and 13 AIDS patients on highly active antiretroviral therapy (HAART), of whom nine were complete responders (CRs) and the remaining four were non‐responders (NRs) to the treatment. TPs but not LTNPs had a significant decrease in absolute counts of circulating Treg, which was inversely correlated with the activation and apoptosis of CD8+ T cells. Efficient HAART was found to increase Treg counts in CR patients and temper the excessive activation and apoptosis of CD8+ T cells. Moreover, isolated Treg significantly inhibited the spontaneous and anti‐CD3‐induced apoptosis of CD8+ T cells in a dose‐dependent manner in vitro. Thus, our findings indicate that the decrease in Treg closely correlates with the increase in apoptotic CD8+ T cells and disease progression in chronic HIV‐1 infection, and that Treg may play a key role in maintaining the balance between the amount and quality of CD8+ T cells in HIV‐1 infection. Manipulation of Treg function may be a promising strategy for immune therapy of this disease.
Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome.

OBJECTIVES Tight control studies including regular assessments of disease activity have shown that this approach has beneficial effects on disease activity, disability and joint damage in treating RA patients. Some of these studies included tight control with protocolized treatment, while others applied tight control without protocolized treatment. The aim of this study was to compare the effects of tight control with usual care and to compare the effects of tight control studies with and without protocolized treatment adjustments. METHODS A systematic literature search was performed to identify clinical trials in RA that evaluated tight control strategies in comparison with usual care. Two types of study were compared: (i) those using disease activity monitoring with protocolized treatment adjustments, and (ii) those using disease activity monitoring without protocolized treatment adjustments. The databases PubMed and Cochrane were searched from 1995 up to 2009. Primary outcome measure was the mean change in the 28-joint DAS (DAS-28), which was used in a random-effects meta-analysis. RESULTS Six controlled trials regarding tight control in RA patients were included in the meta-analysis. In all trials, patients treated in the tight control arms had significantly higher DAS-28 responses than patients treated according to usual care [weighted mean difference (WMD) = 0.59, P < 0.001]. Moreover, tight control was significantly more effective (P < 0.001) by means of protocolized treatment adjustments (WMD = 0.97) compared with non-protocolized monitoring of disease activity (WMD = 0.25). CONCLUSION Tight control in RA resulted in significantly better clinical outcomes than usual care. It is suggested but not proved that tight control with protocolized treatment adjustments is more beneficial than if no such protocol is used.
Gender Discrimination in Relation to Exclusive Breast Feeding Practices amongst Twins in Rural India.

Breastfeeding practices vary among different regions and communities. In India, breastfeeding in rural areas appears to be shaped by the beliefs of a community, which are further influenced by social, cultural, and economic factors. Two hundred mothers along with their twin infants (one male and other female) were enrolled in this study. Only 210 (52 %) neonates had received exclusive breast feeding. Out of the 210 neonates 132 (63 %) male neonates and 78 (37 %) female neonates had received exclusive breast feeding respectively. Gender discrimination regarding feeding practices is prevalent in the rural areas of our country.
Following TRAIL’s path in the immune system

The members of the tumour necrosis factor (TNF) superfamily of cytokines play important roles in the regulation of various immune‐cell functions. Likewise, induction of cell death by apoptosis is indispensable for the normal functioning of the immune system. There are two major pathways of apoptosis induction. The intrinsic, or mitochondrial, pathway is regulated by the activation and interaction of members of the Bcl‐2 family. The extrinsic, or death receptor, pathway is triggered by certain TNF family members when they engage their respective cognate receptors on the surface of the target cell. Hence, cell‐to‐cell‐mediated death signals are induced by activation of these death receptor–ligand systems. Besides TNF itself and the CD95 (Fas/APO‐1) ligand (FasL/Apo1L), the TNF‐related apoptosis‐inducing ligand (TRAIL/Apo2L) belongs to the subfamily of ligands that is responsible for extrinsic induction of cell death. Depending on their status of stimulation, TRAIL can be expressed by various cells of the immune system, amongst them natural killer (NK) cells, T cells, natural killer T cells (NKT cells), dendritic cells and macrophages. TRAIL has been implicated in immunosuppressive, immunoregulatory and immune‐effector functions. With respect to pathological challenges, TRAIL and its receptors have been shown to play important roles in the immune response to viral infections and in immune surveillance of tumours and metastases. In this review we summarize the current knowledge on the role of TRAIL and its receptors in the immune system and, based on this, we discuss future directions of research into the diverse functions of this fascinating receptor–ligand system.
Lifetime socioeconomic status and early life microbial environments predict adult blood telomere length in the Philippines

Psychosocial stress is postulated to hasten senescence in part by accelerating the shortening of telomere length (TL). One pathway through which this may happen is via increasing inflammation and innate immune system activation—a pathway which recent studies suggest acts more strongly for those who grew up in low microbial environments. Thus, we hypothesized that: (1) Psychosocial stress will be inversely associated with TL, (2) early life microbial environments will predict TL, and (3) microbial environments will moderate the association between psychosocial stress and TL.
A CASE OF HEREDITARY ATAXIA (FRIEDREICH) WITH ANATOMIC FINDINGS

CASE REPORT H. G. , a man, born May 22, 1887, apparently was well during early childhood. His father died at the age of 50 from acute nephritis, his mother was living and healthy. The family consisted of one son and three daughters. One of the daughters died in early infancy, the other two were in good health; they were married and had families. Apparently his grandparents lived to an old age. While the family of one of his sisters had not exhibited any hereditary tendencies, two of the children of the other displayed significant symptoms. There was no history of syphilis or tuberculosis in the family. The patient walked and talked at 18 months. At the age of 7 he had measles. Beginning when 6 years, he went to school for seven years and did fairly well with his studies. He then became a machinist's apprentice. When 14 years old
Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction

The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen‐derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider ‘conventional routes’ of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide–Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross‐presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid–CD1 complexes to natural killer T cells and as peptide–Class I MHC complexes to CD8 T cells.
Local irradiation of murine melanoma affects the development of tumour‐specific immunity

Radiation therapy affects the immune system. In addition to killing radiosensitive immune cells, it can induce functional changes in those cells that survive. Our recent studies showed that the exposure of dendritic cells (DCs) to radiation in vitro influences their ability to present tumour antigen in vivo. Here we show that local radiation therapy of B16 melanoma tumours inhibits the development of systemic immunity to the melanoma antigen MART‐1. This inhibition could not be overcome by intratumoral injection of DCs expressing human MART‐1 after radiation therapy, suggesting that a form of immune suppression might have developed. On the other hand, injection of MART‐expressing DCs prior to tumour irradiation was able to prevent inhibition from developing. These results suggest that local radiation therapy may block the generation of immunity under some circumstances and that strategies may be required to prevent this and allow radiation‐induced cell death to translate fully into the development of systemic immunity.
Disparities in work-related injuries associated with worker compensation coverage status.

BACKGROUND This exploratory study addresses patterns of injury in an emerging population of contingent workers who are not covered by either worker's compensation (WC) or health insurance. The primary purpose is to improve the information base regarding the entire population of uninsured, injured workers. Because Latino workers are over-represented in the uninsured group, we include additional characterization of their patterns of injury. Recent studies have found that worker compensation claims and reports address a shrinking proportion of occupational injury and exposure, and about two-thirds of occupational injuries are not captured in the U.S. national surveillance system. METHODS Following the NEISS methodology, a work-relatedness indicator was retrieved for emergency department (ED) visits to an academic health center in fiscal year 2005. RESULTS Twenty percent of self-declared work-related injuries were not associated with self-reported WC coverage. Parametric and non-parametric statistical analysis found several significant disparities in workers without WC. These disparities included a higher proportion of Latinos, workers under age 25, and construction workers. In the uninsured group, Latino workers had a higher proportion of moderate and severe injuries. Nearly all (92 percent) workers without WC also lacked health insurance. Injured low-income workers who lack access to both WC and employer-sponsored health insurance comprise an increasing percentage of the occupationally injured. Our exploratory study found this to be particularly true in high-risk populations. CONCLUSIONS Work-relatedness indicators collected routinely in ED and outpatient settings should be incorporated into standard reporting systems to facilitate more accurate and comprehensive surveillance and better-targeted interventions.
The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1)*

Macrophages play a central role in the balance and efficiency of the immune response and are at the interface between innate and adaptive immunity. Their phenotype is a delicate equilibrium between the M1 (classical, pro-Th1) and M2 (alternative, pro-Th2) profiles. This balance is regulated by cytokines such as interleukin 13 (IL-13), a typical pro-M2-Th2 cytokine that has been related to allergic disease and asthma. IL-13 binds to IL-13 receptor α1 (IL13Rα1), a component of the Type II IL-4 receptor, and exerts its effects by activating the transcription factor signal transducer and activator of transcription 6 (STAT6) through phosphorylation. MicroRNAs are short (∼22 nucleotide) inhibitory non-coding RNAs that block the translation or promote the degradation of their specific mRNA targets. By bioinformatics analysis, we found that microRNA-155 (miR-155) is predicted to target IL13Rα1. This suggested that miR-155 might be involved in the regulation of the M1/M2 balance in macrophages by modulating IL-13 effects. miR-155 has been implicated in the development of a healthy immune system and function as well as in the inflammatory pro-Th1/M1 immune profile. Here we have shown that in human macrophages, miR-155 directly targets IL13Rα1 and reduces the levels of IL13Rα1 protein, leading to diminished activation of STAT6. Finally we also demonstrate that miR-155 affects the IL-13-dependent regulation of several genes (SOCS1, DC-SIGN, CCL18, CD23, and SERPINE) involved in the establishment of an M2/pro-Th2 phenotype in macrophages. Our work shows a central role for miR-155 in determining the M2 phenotype in human macrophages.
CXCR3-B Can Mediate Growth-inhibitory Signals in Human Renal Cancer Cells by Down-regulating the Expression of Heme Oxygenase-1*

The chemokine receptor CXCR3 may play a critical role in the growth and metastasis of tumor cells, including renal tumors. It has been shown that CXCR3 has two splice variants with completely opposite functions; CXCR3-A promotes cell proliferation, whereas CXCR3-B inhibits cell growth. We recently demonstrated that the expression of growth-promoting CXCR3-A is up-regulated, and the growth-inhibitory CXCR3-B is markedly down-regulated in human renal cancer tissues; and the overexpression of CXCR3-B in renal cancer cells can significantly inhibit cell proliferation. However, the growth-inhibitory signal(s) through CXCR3-B are not well characterized. Here, we investigated the effector molecule(s) involved in CXCR3-B-mediated signaling events. We found that the overexpression of CXCR3-B in human renal cancer cells (Caki-1) promoted cellular apoptosis as observed by FACS analysis through Annexin-V staining. To examine whether the overexpression of CXCR3-B could alter the expression of any apoptosis-related genes in renal cancer cells, we performed a protein array. We found that CXCR3-B overexpression significantly down-regulated the expression of antiapoptotic heme oxygenase-1 (HO-1). By utilizing a HO-1 promoter-luciferase plasmid, we showed that CXCR3-B-mediated down-regulation of HO-1 was controlled at the transcriptional level as observed by luciferase assay. We also demonstrated that the inhibition of HO-1 expression using siRNA promoted apoptosis of renal cancer cells. Finally, we observed that human renal cancer tissues expressing low amounts of CXCR3-B significantly overexpress HO-1 at both mRNA and protein level. Together, we suggest that the overexpression of CXCR3-B may prevent the growth of renal tumors through the inhibition of antiapoptotic HO-1.
Suboptimal engagement of the T‐cell receptor by a variety of peptide–MHC ligands triggers T‐cell anergy

T cells recognize antigen via the T‐cell receptor (TCR) and produce a spectrum of responses that range from activation to anergy or cell death. The variety of outcomes may be dictated by the strength of the signals transmitted upon cognate recognition of the TCR. The physiological outcome of TCR engagement is determined by several factors, including the avidity of the ligand for TCR, the duration of engagement, and the presence and nature of accessory molecules present on antigen‐presenting cells (APCs). In this review, we discuss a model of anergy induced by presentation of low densities of peptide–major histocompatibility complex (MHC) ligand in CD4+ T cells and compare it to anergy induced by altered peptide ligands in an effort to identify a unifying mechanism. We suggest that altered peptide ligand (APL) and low densities of agonist ligands induce anergy by engaging less than optimal numbers of TCRs. The physiological impacts of anergy in memory CD4+ T cells are discussed.
Molecular Mimicry of Human Endothelial Cell Antigen by Autoantibodies to Nonstructural Protein 1 of Dengue Virus*

The pathogenesis of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), both serious complications of dengue virus (DV) infection, remains unclear. In this study, we found that anti-DV NS1 (nonstructural protein 1) polyclonal antibodies cross-reacted with human umbilical vein endothelial cells (HUVECs). We further identified a complex-specific mAb, DB16-1, which could recognize DV NS1 and cross-react with HUVECs and human blood vessels. The target protein of DB16-1 was further purified by immunoaffinity chromatography. LC-MS/MS analysis and co-immunoprecipitation revealed that the target protein of DB16-1 was human LYRIC (lysine-rich CEACAM1 co-isolated). Our newly generated anti-LYRIC mAbs bound to HUVECs in a pattern similar to that of DB16-1. The B-cell epitope of DB16-1 displayed a consensus motif, Lys-X-Trp-Gly (KXWG), which corresponded to amino acid residues 116–119 of DV NS1 and mimicked amino acid residues 334–337 in LYRIC. Moreover, the binding activity of DB16-1 in NS1 of DV-2 and in LYRIC disappeared after the KXWG epitope was deleted in each. In conclusion, DB16-1 targeted the same epitope in DV NS1 and LYRIC protein on human endothelial cells, suggesting that it might play a role in the pathogenesis of DHF/DSS. Future studies on the role of the anti-NS1 antibody in causing vascular permeability will undoubtedly be performed on sera collected from individuals before, during, and after the endothelial cell malfunction phase of a dengue illness.
Streptolysin S Contributes to Group A Streptococcal Translocation across an Epithelial Barrier*

Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local suppurative infections and severe invasive diseases. Systemic dissemination of GAS is initiated by bacterial penetration of the epithelial barrier of the pharynx or damaged skin. To gain insight into the mechanism by which GAS penetrates the epithelial barrier, we sought to identify both bacterial and host factors involved in the process. Screening of a transposon mutant library of a clinical GAS isolate recovered from an invasive episode allowed identification of streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS. Of note, the wild type strain efficiently translocated across the epithelial monolayer, accompanied by a decrease in transepithelial electrical resistance and cleavage of transmembrane junctional proteins, including occludin and E-cadherin. Loss of integrity of intercellular junctions was inhibited after infection with a deletion mutant of the sagA gene encoding SLS, as compared with those infected with the wild type strain. Interestingly, following GAS infection, calpain was recruited to the plasma membrane along with E-cadherin. Moreover, bacterial translocation and destabilization of the junctions were partially inhibited by a pharmacological calpain inhibitor or genetic interference with calpain. Our data indicate a potential function of SLS that facilitates GAS invasion into deeper tissues via degradation of epithelial intercellular junctions in concert with the host cysteine protease calpain.