bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression
Authors: de Souza Sales J , Lara F A , Amadeu T P , de Oliveira Fulco T , da Costa Nery J A , Sampaio E P , Pinheiro R O , Sarno E N 
Published: May 2011

SummaryTo elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (IDO) in leprosy, the distribution of IDO-positive cells and IDO activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. An increased number of macrophages/dendritic cells (DC–lineage IDO+ cells were found in lepromatous (LL) compared to tuberculoid (BT) and reversal reaction (RR) patients. IDO-positive cells showing CD68 and CD86 surface markers predominated in LL lesions, while higher levels of IDO activity were observed in the sera of LL versus BT patients. Tests revealed an increased IDO message in Mycobacterium leprae-stimulated peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) and increased IDO expression in M. leprae-stimulated CD14+ cells of both healthy controls (HC) and LL patients, as evaluated via flow cytometry. Increased M. leprae-induced IDO–protein synthesis was also confirmed by Western blot. Based on our in vitro studies, it was confirmed that M. leprae up-regulated IDO expression and activity in HC and LL monocytes. Interferon (IFN)-γ synergized with M. leprae in promoting IDO expression and activity in monocytes. IDO expression induced by both IFN-γ and M. leprae was abrogated by 1-methyltryptophan (1-MT). Our data suggest that M. leprae chronic infection activates the suppressive molecule IDO which, in turn, contributes to the specific immunosuppression observed in LL leprosy.
Association of functional GITR gene polymorphisms related to expression of glucocorticoid-induced tumour necrosis factor-receptor (GITR) molecules with prognosis of autoimmune thyroid disease
Authors: Tomizawa R , Watanabe M , Inoue N , Takemura K , Hidaka Y , Akamizu T , Hayakawa K , Iwatani Y 
Published: May 2011

Summary
The glucocorticoid-induced tumour necrosis factor (TNF)-receptor (GITR) affects the functions of regulatory T (Treg) and effector T (Teff) cells, but the significance of this phenomenon is still unclear. To examine the association of single nucleotide polymorphisms (SNPs) in the GITR gene with the expression of GITR molecules on T cells and with the pathological conditions in patients with autoimmune thyroid disease (AITD), we examined the frequencies of four candidate SNPs in AITD patients and healthy volunteers by restriction enzyme analysis and direct sequence analyses. We also analysed the GITR expression on peripheral Treg and Teff cells in AITD patients by three-colour flow cytometry. The CC genotype in the rs3753348 C/G SNP was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0·0117, odds ratio (OR) = 3·13]. The AA genotype in the rs2298213 A/G SNP was significantly more frequent in patients with mild HD than in patients with severe HD (P = 0·010, OR = 4·43). All patients and healthy individuals had the GG genotype in rs60038293 A/G and rs11466696 A/G SNPs. The proportions of GITR+ cells in Treg and Teff cells were significantly higher in AITD patients with the CC genotype of the rs3753348 SNP than in those with the GG genotype (P = 0·004 and P = 0·011, respectively). In conclusion, the rs3753348 C/G SNP in the GITR is associated with HD prognosis and expression on Treg and Teff cells.
α-Fetoprotein impairs activation of natural killer cells by inhibiting the function of dendritic cells
Authors: Yamamoto M , Tatsumi T , Miyagi T , Tsunematsu H , Aketa H , Hosui A , Kanto T , Hiramatsu N , Hayashi N , Takehara T 
Published: May 2011

Summary
α-Fetoprotein (AFP) is a tumour-associated antigen in hepatocellular carcinoma (HCC). The biological properties of AFP have been identified in its regulatory effects on immune responses of T cells and B cells. However, AFP effects on natural killer (NK) cells are still unclear. In this study, we examined the immunoregulation of AFP on NK activity. The cytolytic activity against K562 cells and Huh7 cells of NK cells co-cultured with AFP-treated dendritic cells (DCs) (AFP-DCs) was lower than that with albumin-treated DCs (Alb-DCs). Direct addition of AFP to NK cells did not alter the cytolytic activity of NK cells. Adding AFP inhibited the interleukin (IL)-12 production of DCs after stimulation with lipopolysaccharide (LPS) [Toll-like receptor (TLR)-4 ligand], or Poly(I:C) (TLR-3 ligand), but not IL-18 production. The mRNAs of IL-12p35 and IL-12p40 were significantly inhibited in AFP-DCs compared with Alb-DCs, but those of TLR-4 or TLR-3 were not. Transwell experiments revealed that soluble factors derived from DCs played roles in inhibition of the ability of activating NK cells by AFP-DCs. Adding the neutralizing antibody of IL-12 to NK cells co-cultured with Alb-DCs resulted in a decrease of cytolytic activity to the levels of NK cells co-cultured with AFP-DCs. Adding IL-12 to NK cells co-cultured with AFP-DCs resulted in an increase of cytolytic activity to the levels of NK cells co-cultured with Alb-DCs. These demonstrated that the impairment of IL-12 production from AFP-DCs resulted in inhibition of the ability of the activation of NK cells by DCs, and thus suggests a role of AFP in HCC development.
Cardiac risk scores in high‐risk Hispanics and the predictive value of BNP
Authors: Macabasco‐O’Connell Aurelia , Danwalder Sara , Sinha Karabi 
Published: May 2011

Aims.  The purpose of this study was to calculate cardiac risk scores in Hispanic subjects and to determine the predictive value of adding B‐type natriuretic peptide in identifying those with asymptomatic left ventricular dysfunction as a measure of cardiovascular disease.Background.  Hispanics have higher rates of cardiovascular risk factors leading to coronary heart disease, asymptomatic left ventricular dysfunction and cardiovascular events. Assessing cardiac risk in these groups is important to identify those at high risk for future cardiovascular events. The use of biomarkers such as B‐type natriuretic peptide may increase the accuracy of risk prediction.Design.  This study used a descriptive, cross‐sectional study design to determine the utility of the standard risk assessment tools (Adult Treatment Panel III and the Framingham Risk Scores risk calculator) and the B‐type natriuretic peptide biomarker to estimate coronary heart disease risk in low‐income, Hispanic participants.Methods.  A sample of 71 patients (age 52 SD 11, 69% female) with multiple cardiovascular risk factors seen at an ambulatory clinic at a county facility was enrolled in the study. Sociodemographic and medical history information were obtained. Two widely used risk calculators (Adult Treatment Panel III and Framingham Risk Scores) were used to estimate 10‐year coronary heart disease risk in each subject. Baseline B‐type natriuretic peptide measurement and echocardiography were performed with each subject to evaluate presence of asymptomatic left ventricular dysfunction. Receiver operating curve analyses were performed to compare predictability, sensitivity and specificity of the traditional risk scores against the B‐type natriuretic peptide level to detect asymptomatic left ventricular dysfunction.Results.  Overall mean risk scores were 5% (SD 5%) (Adult Treatment Panel III) and 10% (SD 7%) (Framingham Risk Scores). Mean B‐type natriuretic peptide levels were 108·5 (SD 191·5) pg/ml. Echocardiogram results revealed a high proportion of subjects with asymptomatic left ventricular dysfunction (74·6%). The receiver operating curves showed an area under the curve of 0·67 for B‐type natriuretic peptide (p < 0·05), 0·64 (p = NS) for Adult Treatment Panel III and 0·56 (p = NS) for Framingham Risk Scores, evidence that B‐type natriuretic peptide does significantly better than Adult Treatment Panel or Framingham Risk Scores in predicting asymptomatic left ventricular dysfunction.Conclusion.  The inclusion of B‐type natriuretic peptide with traditional risk scores may be helpful in predicting risk and asymptomatic left ventricular dysfunction in high‐risk Hispanics.Relevance to clinical practice.  Cardiac risk scores can assist clinicians in identifying patients at high risk for developing coronary heart disease.
Depression is associated with poor functioning in activities of daily living among nursing home residents without cognitive impairment
Authors: Drageset Jorunn , Eide Geir E , Ranhoff Anette H 
Published: May 2011

Aim.  To explore depressive symptoms among nursing home residents without cognitive impairment and the relationship between their depressive symptoms and dependence on activities of daily living, comorbidity and sociodemographic variables.Background.  Depression has become a major health care concern among older people, but depression and its association with functioning in activities of daily living among nursing home residents without cognitive impairment has previously not been studied in Norway.Design.  A cross‐sectional comparative design.Methods.  The sample comprised older residents (age 65–102 years; n = 227) from 30 nursing homes with at least six months of residence. All nursing home residents had a Clinical Dementia Rating scale score ≤0·5 and were capable of conversation. Scores on the Geriatric Depression Scale (15 items) and demographic variables were collected during face‐to‐face interviews. The activities of daily living were assessed using the Katz Index based on nurses’ observation, and medical diagnoses were obtained from the patient records. Pearson’s chi‐square test and ordinal logistic regression were used to identify possible associations between activities of daily living and depression.Results.  After adjustment for age, sex, marital status, length of stay per year and education, more dependence on activities of daily living was associated with depression [odds ratio (OR): 1·18; 95% confidence interval (CI): 1·04–1·37; p = 0·02]. Higher age was associated with less depression (OR: 0·64; 95% CI: 0·43–0·94; p = 0·02), that is, the odds of depression declined by 36% for each 10‐year increase in age.Conclusions.  Our results suggest that depression symptoms are a major health problem among nursing home residents without cognitive impairment and that younger residents are more prone to having depressive symptoms.Relevance to clinical practice.  Nursing home staff should communicate with and observe residents closely for signs of depression, especially younger residents with high dependence on activities of daily living. In addition, formal screening of all residents for depression using an instrument that is sensitive to older people is recommended.
Nursing experience and preference for intuition in decision making
Authors: Pretz Jean E , Folse Victoria N 
Published: May 2011

Aims and objectives.  This article examines the relationship between domain‐specific and domain‐general intuition among practicing nurses and student nurses to determine the role of intuition in nurses’ decision making.Background.  Measures of nursing intuition have not been compared with one another or to measures of general preference for intuition in the psychological literature. Prior research has shown that experienced nurses rely on intuition in clinical judgement, but the various aspects of intuition associated with experience have not been fully explored.Design.  A correlational design was used to examine the factor structures and interrelationships of self‐reported measures of intuition, as well as their relationship to experience.Method.  A web‐based survey was given to 175 practicing nurses and student nurses in the fall of 2007 using measures of intuition from the nursing and psychological literatures. Quantitative analyses employed descriptive and inferential statistics.Results.  Measures of preference for intuition were combined, resulting in the identification of two independent aspects of nursing intuition uniquely related to general intuition and nursing experience. Results revealed that preference for intuition in nursing was not solely due to general preference for intuition and that use of nursing intuition increased with experience.Conclusion.  These results strengthen the knowledge base of decision making in clinical practice by examining differences in preference for use of intuition among nurses. Further interdisciplinary collaboration is recommended.Relevance to clinical practice.  Understanding the use of intuition in clinical judgement will promote professional practice and favourable patient outcomes. If experience simply leads to increased self‐confidence and preference for the use of intuition, this may not actually be related to accuracy in judgement. However, if experience provides valuable information on associations between patient symptoms and outcomes, then the use of intuition in clinical practice should be encouraged.
Testing for causality in covarying traits: genes and latitude in a molecular world
Authors: O’BRIEN CONOR , BRADSHAW WILLIAM E. , HOLZAPFEL CHRISTINA M. 
Published: May 2011

AbstractMany traits are assumed to have a causal (necessary) relationship with one another because of their common covariation with a physiological, ecological or geographical factor. Herein, we demonstrate a straightforward test for inferring causality using residuals from regression of the traits with the common factor. We illustrate this test using the covariation with latitude of a proxy for the circadian clock and a proxy for the photoperiodic timer in Drosophila and salmon. A negative result of this test means that further discussion of the adaptive significance of a causal connection between the covarying traits is unwarranted. A positive result of this test provides a point of departure that can then be used as a platform from which to determine experimentally the underlying functional connections and only then to discuss their adaptive significance.
Clinical and Molecular Characteristics of Immunodysregulation, Polyendocrinopathy, Enteropathy, X‐Linked Syndrome in China
Authors: An Y.‐F. , Xu F. , Wang M. , Zhang Z.‐Y. , Zhao X.‐D. 
Published: May 2011

AbstractImmunodysregulation, polyendocrinopathy, enteropathy, X‐linked (IPEX) syndrome is a rare X‐linked recessive disorder causing life‐threatening systemic autoimmunity because of immunodysregulation. The FOXP3 gene had been reported as the responsible gene, which was critical for the functions of CD4+CD25+FOXP3+ regulatory T cells (Tregs) and maintenance of peripheral immunologic tolerance. So far, no IPEX patients with definite mutations in the FOXP3 gene had been reported in China. In this study, the genotypes and phenotypes were investigated in three IPEX infants from three unrelated Chinese families. Patient 1 (P1) presented with a classical clinical phenotype, whose mutation was a novel frameshift insertion in exon 11, led to the complete abrogation of Tregs. Patient 2 (P2) showed incomplete IPEX phenotype. He carried a missense mutation in exon 11 with slightly increased frequency of Tregs, whereas Patient 3 (P3) presented with a relatively mild classical phenotype and had a previously reported missense mutation in exon 10 with decreased frequency of Tregs. We firstly report three Chinese IPEX patients with definite mutations of FOXP3 gene. Our study indicated the potential correlation between the genotype and the phenotype of IPEX, which was different from the previous reports.
Ex vivo Expansion of CD56+ NK and NKT‐like Lymphocytes from Peripheral Blood Mononuclear Cells of Patients with Ovarian Neoplasia
Authors: Alves P. C. M. , De Angelo Andrade L. A. L. , Petta C. A. , Lorand‐Metze I. , Derchain S. F. , Guimarães F. 
Published: May 2011

AbstractMethods for ex vivo expansion of natural killer (NK) cells have allowed obtaining enough numbers of human NK cells for clinical trials. However, the evaluation of these methods has been mostly limited to haematological malignancies. This study aimed at evaluating a method for selective expansion of NK cells when applied in peripheral blood mononuclear cells (PBMC) of patients with ovarian neoplasia. PBMC from 13 volunteer patients with ovarian neoplasia, seven benign and six malignant tumours, were cultured in CellGro medium supplemented with anti‐CD3 (9–10 initial days), IL‐2 and foetal bovine serum for 21 days. The resulting effector cells were evaluated for their phenotype, cytotoxicity and cytokine secretion. PBMC cultures resulted in multiple populations (NK, NKT and T) of effector cells, enriched with CD56+ lymphocytes. NK cells from patients with benign and malignant ovarian neoplasia were expanded 139.6 ± 63.4 and 82.7 ± 25.3‐fold, respectively, being the largest lymphocyte subtype among CD56+ population. Effector cells expanded from patients with malignant ovarian neoplasia had higher proportion of T lymphocytes and altered cytokine production patterns, characterized by lower INF‐γ, TNF‐α and higher IL‐4, compared with patients with benign ovarian neoplasia. Effector cells were cytotoxic against K562 and OVCAR3 cell lines. Cytotoxicity was significantly higher (P < 0.05) using magnetically separated CD56+ effector cell fractions compared with CD56‐deprived ones. The present study demonstrates the feasibility of the culture system employed to generate effector cells, enriched with CD56+ lymphocytes, from PBMC of patients with ovarian neoplasia. NK cells were the largest lymphocyte subtype among the CD56+ population and the main variable among the final effector cell preparation affecting target cell killing.
Evaluation of the Microbicidal Activity and Cytokines/Chemokines Profile Released by Neutrophils from HTLV‐1‐Infected Individuals
Authors: Bezerra Caroline A. , Cardoso Thiago M. , Giudice Angela , Porto Aurélia F. , Santos Silvane B. , Carvalho Edgar M. , Bacellar Olívia 
Published: May 2011

AbstractHuman T cell lymphotropic virus type‐1 (HTLV‐1) induces activation and spontaneous proliferation of T cells with production of type‐1 pro‐inflammatory cytokines. It modifies the immune response to other antigens and increases susceptibility to infectious diseases. However, little is known about innate immunity in HTLV‐1 infection. HTLV‐1‐infected individuals have higher spontaneous neutrophil activation than HTLV‐1‐seronegative individuals, as shown by the nitroblue tetrazolium (NBT) assay. This study was conducted to evaluate neutrophil function in HTLV‐1‐infected individuals. Participants in the study included 18 HTLV‐1‐infected individuals and 14 HTLV‐1‐seronegative controls. We evaluated the ability of neutrophils (PMNs) to control a parasite infection, to produce peroxynitrite, cytokines and chemokines and to express activation markers in cultures when stimulated with LPS or infected with Leishmania. When compared with the control group, there was no difference in the percentage of PMNs infected with Leishmania or in the number of amastigotes/100 PMNs in HTLV‐1‐infected individuals. The microbicidal activity of the PMNs and the levels of CXCL8 and CCL4 released by these cells did not show a difference between HTLV‐1‐infected individuals and the control group. In both the HTLV‐1 group and the control group, infection with Leishmania or stimulation of PMNs led to cellular activation. These observations suggest that neutrophils from HTLV‐1‐infected individuals have preserved their ability to become activated and to produce chemokines and peroxynitrite after stimulation and that the susceptibility to infection by intracellular Leishmania amazonensis in HTLV‐1‐infected individuals does not depend on impairment of neutrophil function.
Using spontaneous photon emission to image lipid oxidation patterns in plant tissues
Authors: Birtic Simona , Ksas Brigitte , Genty Bernard , Mueller Martin J. , Triantaphylidès Christian , Havaux Michel 
Published: May 2011

SummaryPlants, like almost all living organisms, spontaneously emit photons of visible light. We used a highly sensitive, low‐noise cooled charge coupled device camera to image spontaneous photon emission (autoluminescence) of plants. Oxidative stress and wounding induced a long‐lasting enhancement of plant autoluminescence, the origin of which is investigated here. This long‐lived phenomenon can be distinguished from the short‐lived chlorophyll luminescence resulting from charge recombinations within the photosystems by pre‐adapting the plant to darkness for about 2 h. Lipids in solvent were found to emit a persistent luminescence after oxidation in vitro, which exhibited the same time and temperature dependence as plant autoluminescence. Other biological molecules, such as DNA or proteins, either did not produce measurable light upon oxidation or they did produce a chemiluminescence that decayed rapidly, which excludes their significant contribution to the in vivo light emission signal. Selective manipulation of the lipid oxidation levels in Arabidopsis mutants affected in lipid hydroperoxide metabolism revealed a causal link between leaf autoluminescence and lipid oxidation. Addition of chlorophyll to oxidized lipids enhanced light emission. Both oxidized lipids and plants predominantly emit light at wavelengths higher than 600 nm; the emission spectrum of plant autoluminescence was shifted towards even higher wavelengths, a phenomenon ascribable to chlorophyll molecules acting as luminescence enhancers in vivo. Taken together, the presented results show that spontaneous photon emission imaged in plants mainly emanates from oxidized lipids. Imaging of this signal thus provides a simple and sensitive non‐invasive method to selectively visualize and map patterns of lipid oxidation in plants.
Massively parallel sequencing and identification of genes for primary lymphoedema: a perfect fit
Authors: Ostergaard P , Simpson MA , Jeffery S 
Published: May 2011

Ostergaard P, Simpson MA, Jeffery S. Massively parallel sequencing and the identification of genes for primary lymphoedema: a perfect fit.Primary lymphoedema is a clinically and genetically heterogeneous group of disorders characterized by disruption of the lymphatic system. To date, the majority of the causative genes in primary lymphoedema have been identified through linkage analysis in large families with multiple affected subjects. Studies aimed at isolating additional genes responsible for primary lymphoedema have been hampered by cohorts comprised primarily of sporadic cases and small affected kindreds. In the absence of genetic heterogeneity, recent development of massively parallel DNA sequencing technology, specifically exome sequencing, has provided novel paradigms for disease gene identification in such cohorts. In this review, we summarize the novel approaches to disease gene discovery with massively parallel sequencing also known as Next Generation Sequencing (NGS), and show how the selection of unrelated affected cases from clinically homogenous phenotypic subclassifications is proving to be a successful approach for disease gene discovery in primary lymphoedema.