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- Polarization of ILC2s in Peripheral Blood Might Contribute to Immunosuppressive Microenvironment in Patients with Gastric Cancer. [Journal Article]
- J Immunol Res 2014.:923135.
Newly identified nuocytes or group 2 innate lymphoid cells (ILC2s) play an important role in Th2 cell mediated immunity such as protective immune responses to helminth parasites, allergic asthma, and chronic rhinosinusitis. However, the contributions of ILC2s in the occurrence and development of cancer remain unknown. Our previous study found that there was a predominant Th2 phenotype in patients with gastric cancer. In this study, the ILC2s related genes or molecules in PBMC from patients with gastric cancer were measured, and the potential correlation between them was analyzed. The expression levels of ROR α , GATA3, T1/ST2, IL-17RB, CRTH2, IL-33, IL-5, and IL-4 mRNA were significantly increased in patients, but no significant changes were found in ICOS, CD45, and IL-13 expression, and there was a positive correlation between ROR α or IL-13 and other related factors, such as ICOS and CD45. The increased frequency of ILC2s was also found in PBMC of patients by flow cytometry. In addition, the mRNA of Arg1 and iNOS were also significantly increased in patients. These results suggested that there are polarized ILC2s in gastric cancer patients which might contribute to immunosuppressive microenvironment and closely related to the upregulation of MDSCs and M2 macrophages.
- Longterm follow-up in European respiratory health studies - patterns and implications. [JOURNAL ARTICLE]
- BMC Pulm Med 2014 Apr 16; 14(1):63.
Selection bias is a systematic error in epidemiologic studies that may seriously distort true measures of associations between exposure and disease. Observational studies are highly susceptible to selection bias, and researchers should therefore always examine to what extent selection bias may be present in their material and what characterizes the bias in their material. In the present study we examined long-term participation and consequences of loss to follow-up in the studies Respiratory Health in Northern Europe (RHINE), Italian centers of European Community Respiratory Health Survey (I-ECRHS), and the Italian Study on Asthma in Young Adults (ISAYA).Logistic regression identified predictors for follow-up participation. Baseline prevalence of 9 respiratory symptoms (asthma attack, asthma medication, combined variable with asthma attack and/or asthma medication, wheeze, rhinitis, wheeze with dyspnea, wheeze without cold, waking with chest tightness, waking with dyspnea) and 9 exposure-outcome associations (predictors sex, age and smoking; outcomes wheeze, asthma and rhinitis) were compared between all baseline participants and long-term participants. Bias was measured as ratios of relative frequencies and ratios of odds ratios (ROR).Follow-up response rates after 10 years were 75% in RHINE, 64% in I-ECRHS and 53% in ISAYA. After 20 years of follow-up, response was 53% in RHINE and 49% in I-ECRHS. Female sex predicted long-term participation (in RHINE OR (95%CI) 1.30(1.22, 1.38); in I-ECRHS 1.29 (1.11, 1.50); and in ISAYA 1.42 (1.25, 1.61)), as did increasing age. Baseline prevalence of respiratory symptoms were lower among long-term participants (relative deviations compared to total baseline population 0-15% (RHINE), 0-48% (I-ECRHS), 3-20% (ISAYA)), except rhinitis which had a slightly higher prevalence. Most exposure-outcome associations did not differ between long-term participants and all baseline participants, except lower OR for rhinitis among ISAYA long-term participating smokers (relative deviation 17% (smokers) and 44% (10-20 pack years)).We found comparable patterns of long-term participation and loss to follow-up in RHINE, I-ECRHS and ISAYA. Baseline prevalence estimates for long-term participants were slightly lower than for the total baseline population, while exposure-outcome associations were mainly unchanged by loss to follow-up.
- Effect of inhaled corticosteroids on systemic inflammation in asthma. [Journal Article]
- Perspect Clin Res 2014 Apr; 5(2):75-9.
Recent research using serum high sensitivity C-reactive protein (hs-CRP) has evidenced existence of low grade systemic inflammation in asthmatics whose correlation with various clinical indices is not fully studied.To investigate the relationship between systemic inflammation and various clinical and treatment characteristics of asthma.Forty asthmatics (22 steroid inhaling and 18 steroid naïve) and 40 healthy subjects matched for age and sex were examined cross-sectionally. Along with clinical assessment, serum hs-CRP levels were measured for all subjects using latex enhanced immunoturbidometry method.Serum hs CRP levels were significantly higher in steroid naïve asthmatics when compared to normal subjects (0.93 ± 1.18 vs 0.24 ± 0.31 mg/dL, respectively; Mann-Whitney U test, P < 0.001). This association persisted after adjusting for age, gender, body mass index (BMI), and socioeconomic status (adjusted odds ratio 10.47; 95% CI 1.88-58.3; P < 0.01). Steroid inhaling asthmatics had serum hs-CRP levels comparable with control group (0.17 ± 0.18 vs 0.24 ± 0.31 mg/dL respectively, P > 0.05). Among the clinical and treatment related variables, duration of inhaled steroids usage alone correlated significantly with serum hs-CRP levels (Pearson correlation coefficient r = 0.449, P < 0.05), which was independent of age, BMI, duration of illness, and frequency of emergency visits.This study confirms the existence of low grade systemic inflammation in asthma which is effectively controlled by inhaled steroids. Such an effect of inhaled steroids appears to be more pronounced in recent users than that of long-term users, possibly due to lower adherence rate among the latter.
- Skin Testing and Patch Testing in Non-IgE-Mediated Drug Allergy. [Journal Article]
- Curr Allergy Asthma Rep 2014 Jun; 14(6):442.
Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and prick tests can be done with any commercialized form of a drug. In non-severe delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed readings have a greater value, but their techniques lack standardization. A negative drug skin test does not exclude the responsibility of a drug, and the drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption. Their best indication is in acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms (DRESS). They should be carried out cautiously, following strict guidelines. Prick tests have a low value but they can sometimes be positive on delayed readings. In non-severe delayed reactions to drugs, intradermal tests with delayed readings are the most sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media, heparins but also some biological agents. The value of patch testing varies according to the implicated drug and the non-immediate adverse drug reaction. In DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors but remain negative in testing with allopurinol or salazopyrin. In toxic epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the reported cases.
- Analysis on the Relevance of Asthma Susceptibility with the Alteration of Integrin β 4 Expression. [Journal Article]
- PLoS One 2014; 9(4):e95533.
Accumulated research has suggested the importance of the adhesion molecules modulation as therapeutic approach for bronchial asthma. Adhesion molecules expression alteration contributes to the pathogenesis of asthma. In order to probe the roles of expression imbalance of adhesion molecules in asthma pathogenesis, expression profiling of adhesion molecules was performed using cDNA microarray assay. The results showed that the expression pattern of adhesion molecules was altered in peripheral blood leucocytes of asthma patients. In this study, we focused on one of the abnormally expressed molecule, integrin β4, which was down-regulated in all asthma patients, to analyze the relevance of asthma susceptibility with the alteration of integrin β4 expressions. Real time PCR was used to verify the down-regulation of integrin β4 in additional 38 asthma patients. Next, the 5'flanking region of integrin β4 DNA were amplified, sequenced and site-directed mutagenesis technology in correspondent variation sites were carried out. Among 4 variation sites found in 5' flanking region of integrin β4, 3 were related to asthma susceptibility: -nt1029 G/A, -nt 1051 G/A, and -nt 1164 G/C. A reduction of human integrin β4 promoter activity was observed at mutants of these sites. This study demonstrates that various adhesion molecules in asthma patients are abnormally expressed. Mutations in 5' flanking region result in reduced integrin β4 expression, which is related to increased risk of asthma.
- Immunotherapy Reduces Allergen-Mediated CD66b Expression and Myeloperoxidase Levels on Human Neutrophils from Allergic Patients. [Journal Article]
- PLoS One 2014; 9(4):e94558.
CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation.CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p<0.001). Myeloperoxidase activity in nasal lavage fluid was also significantly reduced by immunotherapy, as were the neutrophil cell-surface expression of CD66b and myeloperoxidase (p<0.001). Interestingly, CD66b expression was higher in neutrophils from nasal lavage fluid than those from peripheral blood, and immunotherapy reduced the number of CD66+MPO+ cells in nasal lavage fluid. Thus, immunotherapy positive effects might, at least in part, be mediated by the negative regulation of the CD66b and myeloperoxidase activity in human neutrophils.
- Human Immune Responses to H. pylori HLA Class II Epitopes Identified by Immunoinformatic Methods. [Journal Article]
- PLoS One 2014; 9(4):e94974.
H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects.
- Unmet needs of patients with chronic obstructive pulmonary disease (COPD): a qualitative study on patients and doctors. [JOURNAL ARTICLE]
- BMC Fam Pract 2014 Apr 16; 15(1):67.
Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation. The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management. However, the evidence on the benefit of self-management in COPD is conflicting. Whether this could be due to other unmet needs of patients have not been investigated. Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD.We conducted a qualitative study with doctors and patients in Malaysia. We used convenience sampling to recruit patients until data saturation. Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide. The interviews were audio-recorded, transcribed verbatim and checked by the interviewers. Data were analysed using a thematic approach.The themes were similar for both the patients and doctors. Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management. Knowledge about COPD was generally poor. Patients were not familiar with the term chronic obstructive pulmonary disease or COPD. The word 'asthma' was used synonymously with COPD by both patients and doctors. Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness. Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care.In conclusion, our study showed that knowledge of COPD is generally poor. There was mislabelling of COPD as asthma by both patients and physicians. This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD. The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation. Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit.
- An Ethnobotanical study of Medicinal Plants in high mountainous region of Chail valley (District Swat- Pakistan). [JOURNAL ARTICLE]
- J Ethnobiol Ethnomed 2014 Apr 16; 10(1):36.
This paper represents the first ethnobotanical study in Chail valley of district Swat-Pakistan and provides significant information on medicinal plants use among the tribal people of the area. The aim of this study was to document the medicinal uses of local plants and to develop an ethnobotanical inventory of the species diversity.In present study, semi-structured interviews with 142 inhabitants (age range between 31-75 years) were conducted. Ethnobotanical data was analyzed using relative frequency of citation (RFC) to determine the well-known and most useful species in the area.Current research work reports total of 50 plant species belonging to 48 genera of 35 families from Chail valley. Origanum vulgare, Geranium wallichianum and Skimmia laureola have the highest values of relative frequency of citation (RFC) and are widely known by the inhabitants of the valley. The majority of the documented plants were herbs (58%) followed by shrubs (28%), trees (12%) and then climbers (2%). The part of the plant most frequently used was the leaves (33%) followed by roots (17%), fruits (14%), whole plant (12%), rhizomes (9%), stems (6%), barks (5%) and seeds (4%). Decoction was the most common preparation method use in herbal recipes. The most frequently treated diseases in the valley were urinary disorders, skin infections, digestive disorders, asthma, jaundice, angina, chronic dysentery and diarrhea.This study contributes an ethnobotanical inventory of medicinal plants with their frequency of citations together with the part used, disease treated and methods of application among the tribal communities of Chail valley. The present survey has documented from this valley considerable indigenous knowledge about the local medicinal plants for treating number of common diseases that is ready to be further investigated for biological, pharmacological and toxicological screening. This study also provides some socio-economic aspects which are associated to the local tribal communities.