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Gastric cancer is a challenging public health concern worldwide and remains a leading cause of cancer-related mortality. The primary risk factor implicated in gastric cancer development is infection with Helicobacter pylori . H. pylori induces chronic inflammation affecting the gastric epithelium, which can lead to DNA damage and the promotion of precancerous lesions. Disease manifestations associated with H. pylori are attributed to virulence factors with multiple activities, and its capacity to subvert host immunity. One of the most significant H. pylori virulence determinants is the cagPAI gene cluster, which encodes a type IV secretion system and the CagA toxin. This secretion system allows H. pylori to inject the CagA oncoprotein into host cells, causing multiple cellular perturbations. Despite the high prevalence of H. pylori infection, only a small percentage of affected individuals develop significant clinical outcomes, while most remain asymptomatic. Therefore, understanding how H. pylori triggers carcinogenesis and its immune evasion mechanisms is critical in preventing gastric cancer and mitigating the burden of this life-threatening disease. This review aims to provide an overview of our current understanding of H. pylori infection, its association with gastric cancer and other gastric diseases, and how it subverts the host immune system to establish persistent infection.

H. pylori is perhaps the most prevalent human pathogen worldwide and infects almost half of the world's population. Despite the decreasing prevalence of infection overall, it is significant in developing countries. Most infections are acquired in childhood and persist for a lifetime unless treated. Children are often asymptomatic and often develop a tolerogenic immune response that includes T regulatory cells and their products, immunosuppressive cytokines, such as interleukin (IL)-10, and transforming growth factor-β (TGF-β). This contrasts to the gastric immune response seen in H. pylori -infected adults, where the response is mainly inflammatory, with predominant Th1 and Th17 cells, as well as, inflammatory cytokines, such as TNF-α, IFN-γ, IL-1, IL-6, IL-8, and IL-17. Therefore, compared to adults, infected children generally have limited gastric inflammation and peptic ulcer disease. H. pylori surreptitiously subverts immune defenses to persist in the human gastric mucosa for decades. The chronic infection might result in clinically significant diseases in adults, such as peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. This review compares the infection in children and adults and highlights the H. pylori virulence mechanisms responsible for the pathogenesis and immune evasion., Competing Interests: CONFLICTS OF INTEREST STATEMENT: The author has no conflicts of interest to declare.

Background: Hyperhomocysteinemia, a thrombotic risk factor, may have several causes. Among the genetic causes of hyperhomocysteinemia, there are polymorphisms in the enzymes methylenetetrahydrofolate reductase (C677T) and cystathionine β-synthase (C699T, C1080T, and 844ins68). Although the frequency of hyperhomocysteinemia in our country is high, there is no evidence about the frequencies of these polymorphisms., Methods: We analyzed 80 healthy individuals from several regions in our country. We evaluated the fasting and post-oral methionine load plasma Hcy and the genotypes in order to obtain the allele frequencies of the polymorphisms C677T of methylenetetrahydrofolate reductase and C699T, C1080T, and 844ins68 of the cystathionine β-synthase., Results: No individual had deficiency of folic acid, vitamins B12, or B6, but 80% had post-oral methionine load hyperhomocysteinemia. We found a significant increase in the Hcy plasma concentration associated with age and gender. Only the polymorphism C1080T was significantly associated with hyperhomocysteinemia., Conclusion: There is an association between fasting and post-oral methionine load plasma Hcy concentrations with the allelic frequencies of the polymorphisms C669T, 844ins68, and C1080T of the cystathionine β-synthase and C667T of the methylenetetrahydrofolate reductase in healthy Mexican individuals. As compared with individuals with normal fasting or post-oral methionine load Hcy plasma levels, only C1080T was significantly associated with hyperhomocysteinemia., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Helicobacter pylori ( H. pylori ) is a gram negative bacterium that infects more than 50% of humanity and is associated with gastritis, peptic ulcer and gastric cancer. Although CD4 + T cells are recruited to the gastric mucosa, the host is unable to clear the bacteria. Previously, we demonstrated that H. pylori infection upregulates the expression of the T cell co-inhibitory molecule B7-H1 while simultaneously downregulating the expression of T cell co-stimulatory molecule B7-H2 on gastric epithelial cells (GEC), which together affect the Treg and Th17 cell balance and foster bacterial persistence. Because B7-H3, another member of the B7 family of co-inhibitory receptors, has been found to have important immunoregulatory roles and in cancer, in this study we examined the expression of B7-H3 molecules on GEC and how the expression is regulated by H. pylori during infection. Our study showed that both human and murine GEC constitutively express B7-H3 molecules, but their expression levels increased during H. pylori infection. We further demonstrated that H. pylori uses its type 4 secretion system (T4SS) components CagA and cell wall peptidoglycan (PG) fragment to upregulate B7-H3. Th17 cells and Treg cells which are increased during H. pylori infection also had an effect on B7-H3 induction. The underlying cell signaling pathway involves modulation of p38MAPK pathway. Since B7-H3 were shown to up-regulate Th2 responses, the phenotype of T cell subpopulations in mice infected with H. pylori PMSS1 or SS1 strains were characterized. A mixed Th1/Th2 response in H. pylori infected mice was observed. Consistent with previous findings, increased Treg cells and decreased Th17 cells in MLN of PMSS1 infected mice compared to SS1 infected mice was observed. Human biopsy samples collected from gastritis biopsies and gastric tumors showed a strong association between increased B7-H3 and Th2 responses in H. pylori strains associated with gastritis. T cell: GEC co-cultures and anti-B7-H3 blocking Ab confirmed that the induction of Th2 is mediated by B7-H3 and associated exclusively with an H. pylori gastritis strain not cancer or ulcer strains. In conclusion, these studies revealed a novel regulatory mechanism employed by H. pylori to influence the type of T cell response that develops within the infected gastric mucosa.

Helicobacter pylori is a prevalent human pathogen that successfully establishes chronic infection, which leads to clinically significant gastric diseases including chronic gastritis, peptic ulcer disease (PUD), and gastric cancer (GC). H. pylori is able to produce a persistent infection due in large part to its ability to hijack the host immune response. The host adaptive immune response is activated to strategically and specifically attack pathogens and normally clears them from the infected host. Since B and T lymphocytes are central mediators of adaptive immunity, in this chapter we review their development and the fundamental mechanisms regulating their activation in order to understand how some of the normal processes are subverted by H. pylori. In this review, we place particular emphasis on the CD4 + T cell responses, their subtypes, and regulatory mechanisms because of the expanding literature in this area related to H. pylori. T lymphocyte differentiation and function are finely orchestrated through a series of cell-cell interactions, which include immune checkpoint receptors. Among the immune checkpoint receptor family, there are some with inhibitory properties that are exploited by tumor cells to facilitate their immune evasion. Gastric epithelial cells (GECs), which act as antigen-presenting cells (APCs) in the gastric mucosa, are induced by H. pylori to express immune checkpoint receptors known to sway T lymphocyte function and thus circumvent effective T effector lymphocyte responses. This chapter reviews these and other mechanisms used by H. pylori to interfere with host immunity in order to persist.

Background and Aims: The role of programmed cell death protein 1 (PD-1) and its ligands in the dysregulation of T helper immune responses observed in the inflammatory bowel disease (IBD) is unclear. Recently, a novel concept emerged that CD90 + colonic (myo)fibroblasts (CMFs), also known as stromal cells, act as immunosuppressors, and are among the key regulators of acute and chronic inflammation. The objective of this study was to determine if the level of the PD-1 ligands is changed in the IBD inflamed colonic mucosa and to test the hypothesis that changes in IBD-CMF-mediated PD-1 ligand-linked immunosuppression is a mechanism promoting the dysregulation of Th1 cell responses., Methods: Tissues and cells derived from Crohn's disease (CD), ulcerative colitis (UC), and healthy individuals (N) were studied in situ, ex vivo , and in culture., Results: A significant increase in programmed death-ligand 1 (PD-L1) was observed in the inflamed UC colonic mucosa when compared to the non-inflamed matched tissue samples, CD, and healthy controls. UC-CMFs were among the major populations in the colonic mucosa contributing to the enhanced PD-L1 expression. In contrast, PD-L1 expression was decreased in CD-CMFs. When compared to CD-CMFs and N-CMFs, UC-CMFs demonstrated stronger suppression of IL-2, Th1 transcriptional factor Tbet, and IFN-γ expression by CD3/CD28-activated CD4 + T cells, and this process was PD-L1 dependent. Similar observations were made when differentiated Th1 cells were cocultured with UC-CMFs. In contrast, CD-CMFs showed reduced capacity to suppress Th1 cell activity and addition of recombinant PD-L1 Fc to CD-CMF:T cell cocultures partially restored the suppression of the Th1 type responses., Conclusion: We present evidence showing that increased PD-L1 expression suppresses Th1 cell activity in UC. In contrast, loss of PD-L1 expression observed in CD contributes to the persistence of the Th1 inflammatory milieu in CD. Our data suggest that dysregulation of the Th1 responses in the inflamed colonic mucosa of IBD patients is promoted by the alterations in PD-L1 expression in the mucosal mesenchymal stromal cell compartment.

Background: Almost 10% of women in reproductive age had a chronic disease, and contraception is frequently ignored by these patients. The lack of use of contraceptives methods has a higher repercussion in these patients; if pregnant, the risk is increased in morbidity and feto-maternal mortality., Objectives: to know the contraceptive coverage in women with chronic degenerative diseases, the kind of contraceptive methods and the unsatisfied demand., Material and Methods: A descriptive study was made with the application of a survey from the one elaborated by the IMSS. It explores contraception socio-demographic data, causes of non-protection and also explores Medical Doctor (MD) participation. Sample size was calculated in 385 women in reproductive age with a chronic disease., Results: 428 women about 30-49 years old were interviewed, 53% of them were married, they had various diseases, the contraceptive coverage was 84%. The definitive methods were the most used with 47%, followed by the condom with 20%, intrauterine device with 13% and others in minor proportion. 38.5% of patients with sexual life have risk of pregnancy for lack of use of method or for using one of low effectiveness and continuity. Of 45 (16%) patients with sexual life that did not use methods, 29% because they wish pregnancy, 18% by collateral effects and the rest for other causes. From this same patients 21 wished getting pregnant and 24 did not, this is an unsatisfied demand of 53%. The MD's informed about risks in case of pregnancy of 83.4% of the patients., Conclusions: The contraceptive coverage is low and the unsatisfied demand is higher than in the general population. It requires the effective participation of health personal in this group of high reproductive risk.

Background: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B-vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency., Objective: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia., Methods: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non-parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules., Results: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk., Conclusion: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism.

Objective: To assess IR in PCOS patients, using the HE-clamp as the IR gold standard., Material and Methods: A transversal design was done. All patients who accepted to participate provided written informed consent. PCOS was diagnosed according to the 2003 Rotterdam criteria. IR was assessed using the H-clamp, and other IR surrogates such as; fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index and insulin/ glucose rate (I/G rate). Statistical analysis was performed using measures of location and spread was used according to data distribution., Results: 21 patients were included. The mean age of the total group studied was 29.5 +/- 4.8 years, and the body mass index (BMI) was 27.2 +/- 3.08 kg/m2. The 85.7% of the patients met the three Rotterdam criteria for the diagnosis of PCOS. According to the HE clamp 95.2% were IR (M/I value < 6 mg/Kg/min), in contrast the prevalence of IR using sur- rogates was 47.6%, 33.3%, and 66.6% for FPI, G/I rate, and HOMA index respectively., Conclusions: Our findings show that IR is highly prevalent in patients with PCOS, and that this prevalence is even higher when insulin sensitivity is assessed using the glucose clamp technique. This evidence suggests that IR could be considered diagnostic criteria for PCOS.

The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world's population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori's avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori.

Helicobacter pylori (H. pylori) is perhaps the most ubiquitous and successful human pathogen, since it colonizes the stomach of more than half of humankind. Infection with this bacterium is commonly acquired during childhood. Once infected, people carry the bacteria for decades or even for life, if not treated. Persistent infection with this pathogen causes gastritis, peptic ulcer disease and is also strongly associated with the development of gastric cancer. Despite induction of innate and adaptive immune responses in the infected individual, the host is unable to clear the bacteria. One widely accepted hallmark of H. pylori is that it successfully and stealthily evades host defense mechanisms. Though the gastric mucosa is well protected against infection, H. pylori is able to reside under the mucus, attach to gastric epithelial cells and cause persistent infection by evading immune responses mediated by host. In this review, we discuss how H. pylori avoids innate and acquired immune response elements, uses gastric epithelial cells as mediators to manipulate host T cell responses and uses virulence factors to avoid adaptive immune responses by T cells to establish a persistent infection. We also discuss in this review how the genetic diversity of this pathogen helps for its survival.

Signaling via programmed death ligand-1 (PD-L1) and PD-L2 is crucial for maintaining peripheral tolerance. CD90(+) myofibroblasts/fibroblasts (CMFs) are major programmed cell death-1 (PD-1) ligand-expressing cells in normal human colonic mucosa. CMFs suppress activated CD4(+) T cell proliferation via PD-1 ligands. It is not known whether signaling through TLRs contribute to the regulation PD-1 ligands on CMFs upon colonic mucosal tolerance. In this study, we demonstrated that stimulation of TLR4 on human CMFs upregulates PD-L1, but not PD-L2, and reinforces CMF-mediated suppression of CD4(+) T cell proliferation and IFN-γ production. TLR4-mediated upregulation of PD-L1 on CMFs involved NF-κB pathways and was JAK2 and MyD88 dependent. MyD88-dependent stimulation of TLR1/2 and TLR5 also upregulated PD-L1 expression on CMFs in culture. PD-L1 expression was drastically decreased in vivo in the colonic mucosa of mice devoid of MyD88. Induction of MyD88 deficiency in CMFs in fibroblast-specific MyD88 conditional knockout mice resulted in a strong increase in a mucosal IFN-γ expression concomitantly with the abrogation of PD-L1 expression in CMFs under homeostasis and epithelial injury induced by dextran sodium sulfate. Together, these data suggest that MyD88-dependent TLR stimulation of CMFs in the normal colonic mucosa may reinforce these cells' anti-inflammatory capacity and thus contribute to the maintenance of mucosal tolerance., (Copyright © 2014 by The American Association of Immunologists, Inc.)

Background: The development of accurate classification models depends upon the methods used to identify the most relevant variables. The aim of this article is to evaluate variable selection methods to identify important variables in predicting a binary response using nonlinear statistical models. Our goals in model selection include producing non-overfitting stable models that are interpretable, that generate accurate predictions and have minimum bias. This work was motivated by data on clinical and laboratory features of Helicobacter pylori infections obtained from 60 individuals enrolled in a prospective observational study., Results: We carried out a comprehensive performance comparison of several nonlinear classification models over the H. pylori data set. We compared variable selection results by Multivariate Adaptive Regression Splines (MARS), Logistic Regression with regularization, Generalized Additive Models (GAMs) and Bayesian Variable Selection in GAMs. We found that the MARS model approach has the highest predictive power because the nonlinearity assumptions of candidate predictors are strongly satisfied, a finding demonstrated via deviance chi-square testing procedures in GAMs., Conclusions: Our results suggest that the physiological free amino acids citrulline, histidine, lysine and arginine are the major features for predicting H. pylori peptic ulcer disease on the basis of amino acid profiling.

We report (nanosecond) resonance-enhanced multiphoton ionization (REMPI), (nanosecond) zero-kinetic-energy (ZEKE) and (picosecond) time-resolved slow-electron velocity map imaging (tr-SEVI) spectra of fully hydrogenated toluene (Tol-h8) and the deuterated-methyl group isotopologue (α3-Tol-d3). Vibrational assignments are made making use of the activity observed in the ZEKE and tr-SEVI spectra, together with the results from quantum chemical and previous experimental results. Here, we examine the 700-1500 cm(-1) region of the REMPI spectrum, extending our previous work on the region ≤700 cm(-1). We provide assignments for the majority of the S1 and cation bands observed, and in particular we gain insight regarding a number of regions where vibrations are coupled via Fermi resonance. We also gain insight into intramolecular vibrational redistribution in this molecule.

It has been reported that infertility affects approximately 20% of couples in reproductive age around the world. Although many factors involved, ovulatory dysfunction and particularly the hypothalamus pituitary dysfunction are quite common. The first line treatment for these pathologies consists on the administration of inducing ovulation agents such as recombinant gonadotropins and clomiphene citrate which it was obtained high rates of ovulation but not of pregnancy. So determine the effect of these treatments on the endometrium at morphological and molecular level is very important to understand the female reproductive physiology and optimize clinical strategies to obtain better pregnancy rates after treatments. In this paper we detailed the studies that have reported changes at the molecular and morphological level in human endometrium.

Background: Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment., Objective: Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia., Method: It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia., Results: During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here., Conclusions: It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.

We have recorded (1+1) resonance-enhanced multiphoton ionization spectra of complexes formed between NO and the alkanes: CH(4), C(2)H(6), C(3)H(8), and n-C(4)H(10). The spectra correspond to the à ← X̃ transition, which is a NO-localized 3s ← 2pπ* transition. In line with previous work, the spectrum for NO-CH(4) has well-defined structure, but this is only partially resolved for the other complexes. The spectra recorded in the NO(+)-alkane mass channels all show a slowly rising onset, followed by a sharp offset, which is associated with dissociation of NO-alkane, from which binding energies in the X̃ and à states are deduced. Beyond this sharp offset, there is a further rise in signal, which is attributed to fragmentation of higher complexes, NO-(alkane)(n). Analysis of these features allows binding energies for (NO-alkane)···alkane to be estimated, and these suggest that in the NO-(alkane)(2) complexes, the second alkane molecule is bound to the first, rather than to NO. Calculated structures for the 1:1 complexes are reported, as well as binding energies.

Gastric epithelial cells (GECs) express the class II major histocompatibility complex (MHC) and costimulatory molecules, enabling them to act as antigen-presenting cells (APCs) and affect local T cell responses. During Helicobacter pylori infection, GECs respond by releasing proinflammatory cytokines and by increasing the surface expression of immunologically relevant receptors, including class II MHC. The CD4(+) T cell response during H. pylori infection is skewed toward a Th1 response, but these cells remain hyporesponsive. Activated T cells show decreased proliferation during H. pylori infection, and CD4(+) CD25(+) FoxP3(+) regulatory T cells (Tregs) are present at the site of infection. In this study, we examined the mechanisms surrounding the CD4(+) T cell responses during H. pylori infection and found that transforming growth factor β (TGF-β) plays a major role in these responses. GECs produced TGF-β1 and TGF-β2 in response to infection. Activated CD4(+) T cells in culture with H. pylori-treated GECs were decreased in proliferation but increased upon neutralization of TGF-β. Naïve CD4(+) T cell development into Tregs was also enhanced in the presence of GEC-derived TGF-β. Herein, we demonstrate a role for GEC-produced TGF-β in the inhibition of CD4(+) T cell responses seen during H. pylori infection.

Background: Women's reproductive potential is closely related to nutritional status. Some of the molecules that participate in ovarian regulation are produced in the adipose tissue, and therefore their production is associated with adiposity., Objective: To determine serum leptin, adiponectin, C-reactive protein, interleukin-6, and tumor necrosis factor alpha in infertile women with or without insulin resistance; and to associate these molecules with adiposity., Methods: Thirty-one infertile women were included. Nutritional status was evaluated through clinical and biochemical parameters. Patients were stratified according with their body mass index and the presence of insulin resistance. For statistics, parametric analyses were conducted., Results: The prevalence of overweight was 67.5%; high adiposity was present in 92.3% and central distribution of fat in 96.2% of studied women. Hypercholesterolemia was found in 32.3% of patients, hypertriglyceridemia in 25.8%, and 61.3% presented hyperinsulinemia. Overweight women presented lower adiponectin, and higher TNF-alpha and C-reactive protein concentrations, than those with normal body mass index (p < 0.05). Overweight women had also a higher probability for insulin resistance (p = 0.04). These women with insulin resistance presented lower adiponectin and higher C-reactive protein concentrations than non insulin resistance women. Body mass index correlated with leptin (r= 0.41), TNF-alpha (r= 0.41), and C-reactive protein (r= 0.33) concentrations., Conclusion: The prevalence of overweight, high adiposity, dislipidemias, and IR was high in our population studied. We conclude that adiposity is closely associated with some of the molecules that participate in the reproductive process and that also regulate inflammatory responses.

During Helicobacter pylori infection, T cells are recruited to the gastric mucosa, but the host T-cell response is not sufficient to clear the infection. Some of the recruited T cells respond in a polarized manner to a Th1 response, while others become anergic. We have previously shown that T-cell anergy may be induced during infection by the interaction of T cells with B7-H1, which is up-regulated on the gastric epithelium during H. pylori infection. Recently, regulatory T (Treg) cells with a CD4(+) CD25(high) FoxP3(+) phenotype were found at an increased frequency in the gastric mucosa of biopsy specimens from H. pylori-infected patients. While Treg cells are important in maintaining tolerance, they can also suppress immune responses during infection. In this study, we examined the induction of the Treg phenotype when naïve T cells were incubated with gastric epithelial cells exposed to H. pylori. The frequency of this phenotype was markedly decreased when B7-H1 was blocked with monoclonal antibodies or its expression was blocked with small interfering RNA. The functional role of these Treg cells was assessed in proliferation assays when the cells were cocultured with activated T cells, which effectively decreased proliferation of the cells.

Aim: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection., Methods: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively., Results: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface., Conclusion: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has recently been implicated in carcinogenesis. Helicobacter pylori, which is closely linked to gastric cancer, induces the gastric epithelium to produce proinflammatory cytokines, including MIF. MIF can bind to CD74, which we have previously shown to be highly expressed on the surface of gastric epithelial cells (GEC) during H. pylori infection. In this study, we sought to investigate the role of the H. pylori-induced MIF on epithelial proliferation and procarcinogenic events. Upon establishing a role for the H. pylori CagA virulence factor in MIF production, MIF binding to CD74 on GEC was confirmed. rMIF and H. pylori were shown to increase GEC proliferation, which was decreased when cagA- strains were used and when CD74 was blocked by mAbs. Apoptosis was also decreased by MIF, but increased by cagA- strains that induced much lower amounts of MIF than the wild-type bacteria. Furthermore, MIF binding to CD74 was also shown to decrease p53 phosphorylation and up-regulate Bcl-2 expression. This data describes a novel system in which an H. pylori virulence factor contributes to the production of a host factor that in turn up-regulates procarcinogenic events by the gastric epithelium.

The pathogenesis associated with Helicobacter pylori infection is the result of both bacterial factors and the host response. We have previously shown that H. pylori binds to CD74 on gastric epithelial cells. In this study, we sought to identify the bacterial protein responsible for this interaction. H. pylori urease from a pool of bacterial surface proteins was found to coprecipitate with CD74. To determine how urease binds to CD74, we used recombinant urease A and B subunits. Recombinant urease B was found to bind directly to CD74 in immunoprecipitation and flow cytometry studies. By utilizing both recombinant urease subunits and urease B knockout bacteria, the urease B-CD74 interaction was shown to induce NF-kappaB activation and interleukin-8 (IL-8) production. This response was decreased by blocking CD74 with monoclonal antibodies. Further confirmation of the interaction of urease B with CD74 was obtained using a fibroblast cell line transfected with CD74 that also responded with NF-kappaB activation and IL-8 production. The binding of the H. pylori urease B subunit to CD74 expressed on gastric epithelial cells presents a novel insight into a previously unrecognized H. pylori interaction that may contribute to the proinflammatory immune response seen during infection.

Background: Some cytokines that take part in the ovarian cycle regulation, such as IL-1beta, IL-6 and TNF-alpha play an important role during growth and development of ovarian follicle. Quantification of some cytokines is promissory in the work-up of ovarian reproductive pathology., Objective: To determine serum levels of IL-1beta, IL-6 and TNF-alpha in infertile patients with ovarian dysfunction and to compare them with those found in ovulatory patients., Patients and Methods: We conducted a cross-sectional study in infertile patients with premature ovarian failure, diminished ovarian reserve, chronic anovulation and ovulatory patients that were well-characterized by clinical and hormonal parameters. We determined serum concentrations of IL-1beta, IL-6 and TNF-alpha by an ELISA method. Statistics was conducted by using one way ANOVA, Kruskall-Wallis and Pearson correlation analyses., Results: We studied a total of forty patients. The mean age was 30 years; we did not find significant differences among groups. Overall mean of cytokines concentration was: 13.2 pg/mL for IL-1beta; 8.4 pg/mL for IL-6; and 1.5 pg/mL for TNF-alpha. We observed a significant difference in the concentration of TNF-alpha in the premature ovarian failure group when it was compared to the control group. Pearson correlation coefficients were no significant., Conclusion: A wide range of dispersion of serum cytokines concentration was observed. Serum concentrations of TNF-alpha in woman with premature ovarian failure were significantly lower than those in the control group. Our findings represent a precedent in the powerful utility of the quantification of these cytokines in reproductive medicine.

Objective: To describe nutritional status, B6, B12, and antioxidant vitamins, as well as homocysteine concentrations in postmenopausal women., Patients and Methods: A cross-sectional study was conducted in Mexico City. One hundred twenty-five women were selected if they were healthy and were in their first five years after menopause onset. Women were spontaneously divided in two groups: women who did not receive any hormonal treatment for at least six months before the study (n = 66), and those who received hormonal treatment at the moment of the study (n = 59). Anthropometry was measured and a fasting blood sample from a peripheral vein was obtained to determine homocysteine, vitamins A, C, E, B6, B12, and folic acid. Results were compared with Student t-test, and a logistic regression model was used to calculate the risk of hyperhomocystinemia after adjusting by some potential confounders., Results: Women who did not receive hormone replacement therapy presented higher body mass index and waist-hip ratio than those who received such treatment. In contrast, this group presented higher prevalence of folic acid deficiency and hyperhomocystinemia, despite they consumed higher amounts of folic acid in the diet. This high risk of hyperhomocystinemia was independent of vitamin serum concentrations and the level of physical activity (OR = 15.1, IC95 = 1.60,141.9)., Conclusions: These results suggest that hormone replacement therapy may protect against overweight and central fat distribution that occur after menopause, but increases the risk of hyperhomocystinemia.

Background: Women with premature ovarian failure often receive hormonal replacement therapy as part of the management strategy. However, it is very unusual for patients to become pregnant while on hormonal therapy., Case: A 33-year-old woman with a history of infertility and secondary amenorrhea was diagnosed with premature ovarian failure. Part of her infertility workup included laparoscopy-hysteroscopy, a dye test with methylene blue, and endometrial and bilateral ovarian biopsy. Two months after completion of this procedure, the patient underwent sonography, which showed an intrauterine pregnancy at 14 weeks' gestation. The pregnancy continued to term, and a healthy infant was born., Conclusion: In most instances the etiology of premature ovarian failure is unknown. In rare cases this condition undergoes spontaneous, reversible remission. One interesting observation in our patient is that despite the performance of invasive diagnostic tests, there were minimal detrimental effects on the patient's pregnancy and infant. This case illustrates that the remote possibility of a spontaneous pregnancy in women with prema- ture ovarian failure should always be considered, and invasive diagnostic procedures should be performed when an intrauterine pregnancy is ruled out with certainty.