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Increased Frequency (increased + frequency)
Selected AbstractsResponse: Increased Frequency of Rolandic Spikes in ADHD ChildrenEPILEPSIA, Issue 5 2004Martin Holtmann No abstract is available for this article. [source] Estimating monthly surface winds for Scania, southern Sweden, using geostrophic wind (1899,1997)GEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 2 2002Marie Ekström Wind direction conditions during the 20th century in Scania, southern Sweden, are investigated using an estimated series of monthly wind vector components (east,west u component and north,south v component). The series is developed from a regression relationship between pairwise (1973 to 1997) monthly averages of 10,m surface wind from Scania and a monthly geostrophic wind, based on mean sea level (MSL) pressure data from the National Center of Atmospheric Research (NCAR). The wind conditions during the 20th century are dominated by winds from southwesterly and westerly directions, particularly during summer and autumn. From the 1980s onwards, increased frequencies of westerly winds are evident in spring and summer; however, similarly large frequencies of westerly winds are also found during the early part of the 20th century. Analysis of the estimated wind series indicates large variation in wind direction during the investigated time period, particularly during 1930 to 1960 when large increases of easterly winds are evident in spring. Increased frequencies of easterly winds were also found in other months during this period but not to the same extent as during the spring season. Thus, the presence of periods with quite different wind characteristics suggests that the overall atmospheric circulation has experienced some shifts in this region during the 20th century. [source] Human epithelial ovarian carcinoma cell-derived cytokines cooperatively induce activated CD4+CD25,CD45RA+ naïve T cells to express forkhead box protein 3 and exhibit suppressive ability in vitroCANCER SCIENCE, Issue 11 2009Xiaofeng Zhao Regulatory T cells play an important role in tumor escape from host antitumor immunity. Increased frequencies of CD4+CD25+ regulatory T cells have been documented in the tumor sites, malignant effusions, and peripheral blood of patients with ovarian carcinoma. However, the mechanism involved remains unclear. In the present study, we collected high-purity human CD4+CD25,CD45RA+ naïve T cells by microbead cell separation. These cells did not express FOXP3 by single-cell analysis, and few cells expressed FOXP3 when they were activated with anti-CD3/CD28 dual signal. However, more cells expressed FOXP3 when the supernatant of human epithelial ovarian carcinoma cell culture was added, yet not the supernatant of normal human ovarian surface epithelia cell culture. Neutralization assays revealed that neutralizing antibody against transforming growth factor , (TGF-,), interleukin-10, and interleukin-4 did not abrogate elevated FOXP3 expression induced by carcinoma cell culture supernatant, whereas neutralizing leukemia inhibitory factor (LIF) partially abrogated FOXP3 expression, but LIF alone could not increase FOXP3 expression in activated naïve T cells. Further, an in vitro coculture suppression assay showed that these cells could suppress the proliferation of autologous CD4+CD25,CD45RA, T cells. In summary, our findings show that ovarian carcinoma cells are able to induce expression of FOXP3 and exhibit suppressive ability in activated naïve T cells by producing soluble substances, and multiple cytokines involve in the induction of FOXP3 expression. (Cancer Sci 2009) [source] Alternatives to standard hemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2007Mark S. MACGREGOR Abstract Survival of patients on hemodialysis remains poor, but the benefits of increasing urea clearance have probably been maximized within our current treatment schedules. Long dialysis sessions (8 hr) produce impressive outcomes, with mortality 53% to 55% lower than conventional schedules. Even increasing from 4 to 5 hr may improve survival. Increased frequency of dialysis (6 times weekly) produces impressive reductions in left ventricular mass and could conceivably be implemented in-center. Preliminary data suggest a 61% reduction in mortality with increased frequency. Nightly dialysis combines longer sessions with increased frequency and has produced remarkable clinical gains in blood pressure, left ventricular mass, serum phosphate, and sleep apnea. However, the data are mainly from case series and impact on mortality remains unknown. Expansion of home hemodialysis would be necessary for this modality to grow. Convective therapies remove middle molecules more effectively, and observational data suggest hemodiafiltration has the potential to improve mortality by 35% to 36%. Hemodiafiltration has the advantage of being relatively easy to implement. The uremic milieu is complex and further investigation of the underlying pathophysiology is needed to inform future dialysis interventions. The survival data above are from observational studies, and hence benefits are likely to be exaggerated. Randomized trials of dialysis interventions are desperately needed. They remain difficult to perform, because of the complexity of both the patient population and the interventions, and because of limited available funding. [source] Alport syndrome: HLA association and kidney graft outcomeINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2004S. Barocci Summary Alport syndrome (AS) is a genetic disease of type IV collagen involving non-homogeneous patterns of inheritance characterized clinically by the presence of progressive haematuric nephritis leading to end-stage renal disease (ESRD), hearing loss and/or ophthalmologic abnormalities. The aim of this study was to investigate, in a cohort of AS patients who had undergone a kidney graft (KG) or who were still on a waiting list for a KG, (a) whether there is a correlation between AS and HLA antigen expression, and (b) long-term graft outcome in transplant patients. The AS cohort was represented by 34 ESRD patients, of whom 25 received a KG and the remaining nine were still on a waiting list. AS transplant patients represented 2.78% of 899 first KGs performed at our centre (Transplantation Department at S. Martino Hospital, Genoa) between 1983 and 2002. Grafts were procured from cadaveric donors in 18 cases and from living, related donors in seven cases. All AS transplant patients had a post-transplant follow-up period of at least 12 months. Results showed that: (i) the frequency of the HLA-DRB1*16 antigen was significantly increased in the whole AS cohort as compared to 128 healthy subjects (HS) (corrected P -value 0.0026; relative risk 7.20) as well as to 232 non-AS ESRD patients on a waiting list for KG (corrected P -values 0.0156; relative risk 4.67); (ii) 5- and 10-year graft survivals in the AS transplant patients were 80 and 73%, respectively, and did not differ from those of a control group represented by 25 non-AS KG recipients matched for sex, age, number of HLA mismatches and immunosuppressive treatment. Increased frequency of HLA-DRB1*16 in AS patients may reflect a linkage disequilibrium with genes coding for collagen synthesis. [source] Increased frequency of IFN-,-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis CJOURNAL OF MEDICAL VIROLOGY, Issue 2 2002Masayuki Murata Abstract To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8+ T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-, (IFN-,), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-, after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-,-producing peripheral CD8+ T cells were found frequently in patients than in controls (P,<,0.05), whereas IL-4-producing peripheral CD8+ T cells were not. Although the frequency of peripheral CD28+CD8+ and CD28,CD8+ T cells in patients was not different from that of controls, CD28+CD8+ T cells exceeded CD28,CD8+ T cells in the capacity for IFN-,-production after mitogenic stimulation (P,<,0.01). In a more detailed analysis of the CD28+CD8+ T cells, CD45RA,CD28+CD8+ T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P,<,0.05). There were no significant correlations between the frequency of IFN-,-producing peripheral CD8+ T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8+ T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8+ T cells are associated with liver damage. J. Med. Virol. 67:162,170, 2002. © 2002 Wiley-Liss, Inc. [source] Association of Helicobacter pylori infection with gastroduodenal disease, epidemiologic factors and iron-deficiency anemia in Turkish children undergoing endoscopy, and impact on growthPEDIATRICS INTERNATIONAL, Issue 6 2007ÖZLEM DURMAZ SÜOGLU Abstract Background: The purpose of the present paper was to investigate the relationship between Helicobacter pylori infection and clinical symptomatology, breast-feeding and socioeconomic level. The relationship between H. pylori and iron-deficiency anemia (IDA) and the effect of H. pylori infection on growth were also investigated. Methods: The subjects consisted of 70 patients aged 4,16 years who underwent upper gastrointestinal endoscopy for recurrent abdominal pain, nausea, vomiting, and dyspeptic complaints during a 2 year period. Patients were divided into two groups according to presence of histological evidence of H. pylori infection (group 1, H. pylori positive; group 2, H. pylori negative) and groups were compared with respect to epidemiologic characteristics, gastrointestinal complaints, height and weight SD scores and IDA. Results: Thirty-five (50%) of the 70 patients participating in the study were H. pylori positive. The mean age of group 1 was significantly higher than that of group 2. There were similar characteristics and symptomatology between groups. The majority of the patients in group 1 belonged to low socioeconomic class (class I and II; P < 0.05). The number of the patients exclusively breast-fed for ,4 months was significantly higher in group 2 than in group 1. Gastritis was significantly more frequent in group 1. Mean hemoglobin, serum Fe and ferritin levels were 11.6 ± 1.7 g/dL, 45.0 ± 23.2 ,g/dL and 11.9 ± 8.4 ,g/dL, respectively, for group 1 and 12.2 ± 0.7 g/dL, 79.3 ± 26.4 ,g/dL and 42.1 ± 31.8 ,g/dL, respectively, for group 2. The mean serum Fe and ferritin levels of group 2 were significantly higher than those of group 1. IDA was observed in 20 (57.1%) and six (17.1%) patients in groups 1 and 2, respectively. IDA was significantly more frequent in group 1. Helicobacter pylori infection was found to be the only variable that had significant effect on IDA. Mean SD height and weight for group 1 were lower than those of the group 2. When the patients were evaluated in four groups according to H. pylori and IDA status, mean height SD score of patients with both H. pylori infection and IDA was significantly lower than that of the patients negative for H. pylori and IDA concomitantly. Conclusion: Low socioeconomic status seems to be an important risk factor for H. pylori infection. Exclusive breast-feeding at least for 4 months can have a protective role against H. pylori infection. Increased frequency of growth retardation and IDA in H. pylori -infected patients in the present study supports similar findings in the literature, although there is still need for detailed studies to clarify the causative mechanisms. [source] Hemostatic and thrombotic markers in patients with hemoglobin E/,-thalassemia diseaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2007Pantep Angchaisuksiri Increased frequency of thrombosis has been observed in patients with hemoglobin E/,-thalassemia (Hb E/,-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/,-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, ,2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/,-thal patients. These changes may account for the increased risk of thrombosis in these patients. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Which duration of postsaccadic slowing identifies anticipatory saccades during smooth pursuit eye movements?PSYCHOPHYSIOLOGY, Issue 2 2001Randal G. Ross Increased frequency of anticipatory saccades during smooth pursuit eye movements is a potential marker of genetic risk for schizophrenia. Postsaccadic slowing criteria are used to separate anticipatory from other types of saccades. However, the necessary duration of slowed pursuit required to identify an anticipatory saccade remains undetermined. We explored the effect of various postsaccadic slowing duration criteria on effect size in a comparison of younger and older schizophrenic and normal adults. For large anticipatory saccades, varying the duration of postsaccadic slowing criteria did not notably change effect size. For smaller leading saccades, a limited 50-ms duration postsaccadic slowing criterion produced the largest effect size (1.54), and maintained a similar effect size across a broad age range. Leading saccades with a limited duration postsaccadic slowing criteria are a possible marker of genetic risk for schizophrenia. [source] Prevalence of and risk factors for prostatitis in African American men: The Flint Men's Health StudyTHE PROSTATE, Issue 1 2009Lauren P. Wallner Abstract INTRODUCTION Prostatitis is a common, yet ill-defined condition without clear diagnostic criteria and treatment strategies. Previous studies examining the prevalence and correlates of prostatitis are limited in their inclusion of primarily white populations. The objective of the current study was to identify prevalence of and risk factors for prostatitis in a population-based sample of African-American men. METHODS In 1996, a probability sample of 703 African-American men, aged 40,79, residing in Genesee County, Michigan without a prior history of prostate cancer/surgery provided responses to a structured interview-administered questionnaire which elicited information regarding sociodemographics, current stress and health ratings, and past medical history, including history of physician diagnosed prostatitis, BPH and sexually transmitted diseases. Logistic regression was used to identify predictors of prostatitis after adjustment for age. RESULTS Forty-seven (6.7%) of the 703 men reported a history of prostatitis. Increased frequency of sexual activity and physical activity were significantly associated with decreased odds of disease. Moderate to severe lower urinary tract symptoms (LUTS) and a history of BPH were significantly associated with prostatitis after adjustment for age. CONCLUSION After adjustment for age, LUTS severity and history of BPH were associated with increased odds of prostatitis. BMI, physical activity and sexual frequency were associated with decreased odds of prostatitis. Finally, poor emotional and physical health, high perceived stress and low social support were associated with an increased risk of prostatitis history. Importantly, these findings suggest that the primary risk factors for this condition are largely modifiable and highlight potential targets for future prevention. Prostate 69: 24,32, 2009. © 2008 Wiley,Liss, Inc. [source] Mortality in a cohort of Danish patients with fibromyalgia: Increased frequency of suicideARTHRITIS & RHEUMATISM, Issue 10 2010Lene Dreyer Objective A previous study demonstrated an association between self-reported widespread body pain and increased mortality. The aim of this study was to analyze whether fibromyalgia (FM) and FM-like symptoms are related to increased mortality. Methods From hospital records, we identified 1,361 patients referred during the period 1984,1999 because of the suspicion of FM. The cases were reviewed by reviewers who were blinded to the outcome. The cohort was followed up for a total of 5,295 person-years at risk and was linked to the Danish Mortality Register. Using the number of years at risk and sex-, age-, and calendar-specific mortality rates from the general population, cause-specific standardized mortality ratios [SMRs] were calculated. Results We observed no overall increased mortality among patients with FM. Among the 1,269 female patients, the SMRs (95% confidence intervals [95% CIs]) for an increased risk of death from suicide, liver cirrhosis/biliary tract disease, and cerebrovascular disease were 10.5 (95% CI 4.5,20.7), 6.4 (95% CI 2.3,13.9), and 3.1 (95% CI 1.1,6.8), respectively. The suicide risk was increased at the time of diagnosis and remained increased after 5 years. Patients meeting the American College of Rheumatology criteria for FM and patients with possible FM had the same cause-specific mortality pattern. No increased cause-specific mortality was observed in the 84 male patients. Conclusion The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup. The results also suggest that risk factors for liver disease and cerebrovascular disease should be evaluated in patients with FM. [source] Increased frequency of extremely skewed X chromosome inactivation in juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 11 2009Elif Uz Objective Juvenile idiopathic arthritis (JIA) is a childhood rheumatic disease of unknown etiology. Two subgroups of JIA, i.e., oligoarticular and polyarticular, are thought to have an autoimmune component, and show a higher female:male ratio. Skewed X chromosome inactivation (XCI) has previously been shown to be associated with scleroderma and autoimmune thyroiditis, 2 autoimmune disorders occurring predominantly in females. This study was undertaken to extend the analysis to the pediatric age group and to determine the XCI profiles of patients with JIA. Methods A polymorphic repeat in the androgen receptor gene was genotyped to determine XCI status in 81 female patients with JIA (21 with polyarticular disease and 60 with oligoarticular disease) and 211 healthy female controls. DNA obtained from venous blood samples was used for this analysis. Results Informative data were obtained on 62 JIA patients and 155 controls. Skewed XCI was observed in 14 patients (22.6%) and 11 controls (7.1%) (P = 0.0036), and extreme skewing was apparent in 8 patients (12.9%) and 2 controls (1.3%) (P = 0.0008). Conclusion Our findings in the present study indicate that skewed XCI may be a risk factor for the occurrence of autoimmune disorders, including JIA. [source] Habitat protection, cattle grazing and density-dependent reproduction in a desert treeAUSTRAL ECOLOGY, Issue 8 2009VALERIA ASCHERO Abstract Anthropogenic activities usually trigger changes in the population density of plants. Thus, land management practices can influence density-dependent demographic parameters and species interactions. We investigated plant-pollinator interactions and reproduction in Prosopis flexuosa, the largest tree species in the Central Monte desert of Argentina, an important economic and cultural resource for humans and a functionally prominent species. We hypothesized that reproductive output of P. flexuosa would be limited at low densities, and that exclusion of catle grazing would enhance population density and consequently interaction frequency with pollinators and reproductive success. The study was conducted in and around Ñacuñán Biosphere Reserve (Mendoza, Argentina), where cattle grazing has been excluded for over 35 years. Working in five pairs of protected and cattle grazed 1-ha plots, we recorded density of adult trees, pollinator visitation frequency to inflorescences and seeds per inflorescence in focal trees. Adult tree density was higher in protected plots than in cattle grazed plots. Density of reproductive trees was positively correlated with seed production, suggesting positive density dependence for reproduction (Allee effect). Pollinator visitation to inflorescences and seed production was higher in protected plots compared with plots under cattle grazing. Suppression of anthropogenic degradation has resulted in higher adult tree density in protected plots, indirectly higher pollinator visitation to inflorescences and higher reproductive success of trees. Increased frequency of plant-pollinator interactions and tree reproduction suggest success of management practices aimed at protecting P. flexuosa woodlands. [source] Increased frequency of intracellular interleukin (IL)-13 and IL-10, but not IL-4, expressing CD4+ and CD8+ peripheral T cells of patients with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2002M. Aleksza Summary Background A number of studies exist demonstrating the increased expression of type 2 cytokines and decreased capacity to produce interferon-, (IFN-,) in peripheral blood mononuclear cells (PBMCs) of patients with atopic dermatitis (AD). Objectives To clarify the results of recent studies concerning the role of interleukin (IL)-4 and IL-13 in PBMCs of AD patients, we analysed the activation status of lymphocyte subpopulations. Methods We measured the intracellular expression and serum levels of certain type 1 and type 2 cytokines, using cell surface and intracellular cytokine staining, flow cytometry and enzyme-linked immunosorbent assay techniques. Results The frequency of IL-10 and IL-13 producing CD4+ and CD8+ T cells was significantly higher in patients with AD, while the frequency of IFN-, secreting helper and cytotoxic T cells was significantly lower in patients with AD than in control subjects. The serum levels of IL-10 and IL-13 were also significantly increased. There were no significant differences observed between the experimental groups in the frequency of IL-4 producing CD4+ and CD8+ cells. Conclusions This study demonstrates a type 2 cytokine production in the CD4+ and CD8+ T cells of AD patients, which is characterized by an elevated IL-13, but not by IL-4 secretion, and by an increased level of the immunoregulatory IL-10, which can contribute to a decrease in IFN-, expression. [source] Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasiaCANCER, Issue 9 2002In vitro, in vivo studies Abstract BACKGROUND Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-, (IFN-,) expression in CD34+ cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-, blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1,3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-,,expressing CD4+ cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3+ MDS cells. Increased numbers of CD34+ cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L,mediated inhibition and the blockade of IFN-, improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-,,expressing CD4+ cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-,blockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS Increased frequency of IFN-, producing CD4+ cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-, production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients. Cancer 2002;95:1911,22. © 2002 American Cancer Society. DOI 10.1002/cncr.10915 [source] Monitoring of DNA breakage in embryonic stages of the African catfish Clarias gariepinus (Burchell, 1822) after exposure to lead nitrate using alkaline comet assayENVIRONMENTAL TOXICOLOGY, Issue 6 2008Alaa G. M. Osman Abstract Increasing lead contamination in Egyptian ecosystems and high lead concentrations in food items have raised concern for human health and stimulated studies on monitoring ecotoxicological impact of lead-caused genotoxicity. In this work, the alkaline comet assay was modified for monitoring DNA strand breakage in sensitive early life stages of the African catfish Clarias gariepinus. Following exposure to 100, 300, and 500 ,g/L lead nitrate, DNA strand breakage was quantified in embryos at 30, 48, 96, 144, and 168 h post-fertilization (PFS). For quantitative analysis, four commonly used parameters (tail % DNA, %TDNA; head % DNA, %HDNA; tail length, TL; tail moment, TM) were analyzed in 96 nuclei (in triplicates) at each sampling point. The parameter %TDNA revealed highest resolution and lowest variation. A strong correlation between lead concentration, time of exposure, and DNA strand breakage was observed. Here, genotoxicity detected by comet assay preceded the manifested malformations assessed with conventional histology. Qualitative evaluation was carried out using five categories are as follows: undamaged (%TDNA , 10%), low damaged (10% < %TDNA , 25%), median damaged (25 < %TDNA , 50%), highly damaged (50 < %TDNA , 75%), and extremely damaged (%TDNA > 75%) nuclei confirming a dose and time-dependent shift towards increased frequencies of highly and extremely damaged nuclei. A protective capacity provided by a hardened chorion is a an interesting finding in this study as DNA damage in the prehatching stages 30 h-PFS and 48 h-PFS was low in all treatments (qualitative and quantitative analyses). These results clearly show that the comet assay is a sensitive tool for the detection of genotoxicity in vulnerable early life stages of the African catfish and is a method more sensitive than histological parameters for monitoring genotoxic effects. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2008. [source] Frequencies of micronuclei in bank voles from zones of high radiation at Chornobyl, UkraineENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2000Brenda E. Rodgers Abstract A population of Clethrionomys glareolus (bank vole) from a highly radioactive area within the Chornobyl, Ukraine exclusion zone was sampled in June 1997 and in June and October 1998. Internal radiation doses from radiocesium were estimated to be as high as 8 rads/d. Total dose, which takes into account the internal dose from radiostrontium and the surrounding environment, was estimated to be 15 to 20 rads/d. In contrast, individuals from a reference population lying outside of the exclusion zone registered negligible levels of contamination. We used the micronucleus test in a double-blind study to analyze blood samples from 58 individuals. We scored more than 600,000 polychromatic erythrocytes (PCEs) but could not reject the null hypothesis that the frequency of micronucleated PCEs in voles exposed to radiation was equal to the frequency in unexposed voles. Results of our study stand in sharp contrast to earlier reports of increased frequencies of micronuclei in rodents exposed to fallout of the Chornobyl accident, but with radiation doses that were orders of magnitude lower than those reported here. Radioresistance and experimental methods are possible explanations for these differences in the results. [source] Case-control single-marker and haplotypic association analysis of pedigree dataGENETIC EPIDEMIOLOGY, Issue 2 2005Sharon R. Browning Abstract Related individuals collected for use in linkage studies may be used in case-control linkage disequilibrium analysis, provided one takes into account correlations between individuals due to identity-by-descent (IBD) sharing. We account for these correlations by calculating a weight for each individual. The weights are used in constructing a composite likelihood, which is maximized iteratively to form likelihood ratio tests for single-marker and haplotypic associations. The method scales well with increasing pedigree size and complexity, and is applicable to both autosomal and X chromosomes. We apply the approach to an analysis of association between type 2 diabetes and single-nucleotide polymorphism markers in the PPAR-, gene. Simulated data are used to check validity of the test and examine power. Analysis of related cases has better power than analysis of population-based cases because of the increased frequencies of disease-susceptibility alleles in pedigrees with multiple cases compared to the frequencies of these alleles in population-based cases. Also, utilizing all cases in a pedigree rather than just one per pedigree improves power by increasing the effective sample size. We demonstrate that our method has power at least as great as that of several competing methods, while offering advantages in the ability to handle missing data and perform haplotypic analysis. Genet. Epidemiol. 28:110,122, 2005. © 2004 Wiley-Liss, Inc. [source] Estimating monthly surface winds for Scania, southern Sweden, using geostrophic wind (1899,1997)GEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 2 2002Marie Ekström Wind direction conditions during the 20th century in Scania, southern Sweden, are investigated using an estimated series of monthly wind vector components (east,west u component and north,south v component). The series is developed from a regression relationship between pairwise (1973 to 1997) monthly averages of 10,m surface wind from Scania and a monthly geostrophic wind, based on mean sea level (MSL) pressure data from the National Center of Atmospheric Research (NCAR). The wind conditions during the 20th century are dominated by winds from southwesterly and westerly directions, particularly during summer and autumn. From the 1980s onwards, increased frequencies of westerly winds are evident in spring and summer; however, similarly large frequencies of westerly winds are also found during the early part of the 20th century. Analysis of the estimated wind series indicates large variation in wind direction during the investigated time period, particularly during 1930 to 1960 when large increases of easterly winds are evident in spring. Increased frequencies of easterly winds were also found in other months during this period but not to the same extent as during the spring season. Thus, the presence of periods with quite different wind characteristics suggests that the overall atmospheric circulation has experienced some shifts in this region during the 20th century. [source] Patients with Epstein Barr virus-positive lymphomas have decreased CD4+ T-cell responses to the viral nuclear antigen 1INTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Kevin N. Heller Abstract Epstein Barr virus (EBV) causes lymphomas in immune competent and, at increased frequencies, in immune compromised patients. In the presence of an intact immune system, EBV-associated lymphomas express in most cases only 3 or fewer EBV antigens at the protein level, always including the nuclear antigen 1 of EBV (EBNA1). EBNA1 is a prominent target for EBV-specific CD4+ T cell and humoral immune responses in healthy EBV carriers. Here we demonstrate that patients with EBV-associated lymphomas, primarily Hodgkin's lymphoma, lack detectable EBNA1-specific CD4+ T-cell responses and have slightly altered EBNA1-specific antibody titers at diagnosis. In contrast, the majority of EBV-negative lymphoma patients had detectable IFN, expression and proliferation by CD4+ T cells in response to EBNA1, and carry EBNA1-specific immunoglobulins at levels similar to healthy virus carriers. Other EBV antigens, which were not present in the tumors, were recognized in less EBV positive, than negative lymphoma patients, but detectable responses reached similar CD8+ T cell frequencies in both cohorts. Patients with EBV-positive and -negative lymphomas did not differ in T-cell responses in influenza-specific CD4+ T cell proliferation and in antibody titers against tetanus toxoid. These data suggest a selective loss of EBNA1-specific immune control in EBV-associated lymphoma patients, which should be targeted for immunotherapy of these malignancies. © 2008 Wiley-Liss, Inc. [source] Oral immunization with Porphyromonas gingivalis outer membrane protein and CpG oligodeoxynucleotides elicits T helper 1 and 2 cytokines for enhanced protective immunityMOLECULAR ORAL MICROBIOLOGY, Issue 3 2010C. Liu Summary The aim of this study was to evaluate the efficacy of an oral vaccine containing the 40-kDa outer membrane protein of Porphyromonas gingivalis (40K-OMP) and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) to control oral infection by P. gingivalis. Oral immunization with 40K-OMP plus CpG ODN induced significant 40K-OMP-specific serum immunoglobulin G (IgG), IgA, and saliva IgA antibody responses. The 40K-OMP-specific CD4+ T cells induced by oral 40K-OMP plus CpG ODN produced both T helper type 1 (Th1; interferon-,) and Th2 (interleukin-4) cytokines. Furthermore, increased frequencies of CD11c+ B220+ dendritic cells (DCs) and CD11c+ CD11b+ DCs with upregulated expression of CD80, CD86, CD40, and major histocompatibility complex class II molecules were noted in spleen, Peyer's patches, and cervical lymph nodes. Immunized mice were then infected orally with P. gingivalis to determine whether the immune responses induced by oral 40K-OMP plus CpG ODN were capable of suppressing the bone resorption caused by P. gingivalis infection. Mice given 40K-OMP plus CpG ODN showed significantly reduced bone loss associated with oral infection by P. gingivalis. Oral administration of 40K-OMP together with CpG ODN induces Th1-type and Th2-type cells, which provide help for protective immunity against P. gingivalis infection. This may be an important tool for the prevention of chronic periodontitis. [source] Brief Definitive Report: Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleenPARASITE IMMUNOLOGY, Issue 7 2010R. MAURYA Summary Natural regulatory T cells (CD4+ CD25+ Foxp3+), natural regulatory T cells (nTreg), play an important role in the regulation of inflammatory immune responses. However, the immunosuppressive properties of nTreg may unfavourably affect the host's ability to clear certain infections. In human visceral leishmaniasis (VL), reports on the frequency and function of nTreg are not conclusive. A limitation of our own previous studies that did not indicate a major role for Foxp3+ nTreg in VL pathogenesis was that Foxp3 was measured by mRNA expression alone, as other tools were not available at the time. We have in this study assessed CD4+CD25+Foxp3+ cells in splenic aspirates and peripheral blood mononuclear cells (PBMC) from an extensive series of patients with VL and endemic controls (EC) by flow cytometry (FACS). The results do not show increased frequencies of Foxp3+ cells in patient with VL pre- and post-treatment, neither were they elevated when compared to PBMC of EC. We conclude that active VL is not associated with increased frequencies of peripheral Foxp3 Treg or accumulation at the site of infection. [source] In Vivo Function of Immune Inhibitory Molecule B7-H4 in Alloimmune ResponsesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010K. Yamaura B7 ligands deliver both costimulatory and coinhibitory signals to the CD28 family of receptors on T lymphocytes, the balance between which determines the ultimate immune response. Although B7-H4, a recently discovered member of the B7 family, is known to negatively regulate T cell immunity in autoimmunity and cancer, its role in solid organ allograft rejection and tolerance has not been established. Targeting the B7-H4 molecule by a blocking antibody or use of B7-H4,/, mice as recipients of fully MHC-mismatched cardiac allografts did not affect graft survival. However, B7-H4 blockade resulted in accelerated allograft rejection in CD28-deficient recipients. B7-1/B7-2-double-deficient recipients are truly independent of CD28/CTLA-4:B7 signals and usually accept MHC-mismatched heart allografts. Blockade of B7-H4 in these mice also precipitated rejection, demonstrating regulatory function of this molecule independent of an intact CD28/CTLA-4:B7 costimulatory pathway. Accelerated allograft rejection was always accompanied by increased frequencies of alloreactive IFN-,-, IL-4- and Granzyme B-producing splenocytes. Finally, intact recipient, but not donor, B7-H4 is essential for prolongation of allograft survival by blocking CD28/CTLA4:B7 pathway using CTLA4-Ig. These data are the first to provide evidence of the regulatory effects of B7-H4 in alloimmune responses in a murine model of solid organ transplantation. [source] Xenobiotic metabolism, genetic polymorphisms and male infertilityANDROLOGIA, Issue 4-5 2000H.-C. Schuppe Male reproductive function may be impaired by various occupational and environmental chemical agents. The majority of these xenobiotics, however, require metabolic activation in order to exert adverse effects via covalent interactions between intermediate metabolites and cellular macromolecules such as DNA or protein. In addition, metabolization may alter endocrine-disrupting properties of xenobiotics. Thus tissue-specific expression and regulation of multiple xenobiotic-metabolizing enzymes are likely to play an important role in chemically induced disorders of male reproductive organs. Recent studies suggest that genetic polymorphisms underlying inter-individual and inter-ethnic variability of xenobiotic metabolism modulate susceptibility to male reproductive disorders. For cytochrome P450 1A1 (CYP1A1), a key enzyme in extra-hepatic metabolic activation of lipophilic xenobiotics, increased frequencies of two genetically linked polymorphisms have been found among infertile men. [source] Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczemaBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2010T. McPherson Summary Background, Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease. Objectives, To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets. Methods, We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses. Results, Filaggrin null mutations associated with significantly (P < 0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses. Conclusions, These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease. [source] Ethanolic leaf extract of neem (Azadirachta indica) inhibits buccal pouch carcinogenesis in hamstersCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2005R. Subapriya Abstract We evaluated the chemopreventive effects of ethanolic neem leaf extract in the initiation and post-initiation phases of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. The frequency of bone marrow micronuclei as well as the concentrations of lipid peroxides, ratio of reduced to oxidized glutathione (GSH/GSSG), and the activities of the GSH-dependent enzymes glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in the buccal pouch, liver and erythrocytes were used as biomarkers of chemoprevention. All the hamsters painted with DMBA alone for 14 weeks developed buccal pouch carcinomas that showed diminished lipid peroxidation and enhanced antioxidant status associated with increased frequencies of bone marrow micronuclei. In the liver and erythrocytes of tumour-bearing animals, enhanced lipid peroxidation was accompanied by compromised antioxidant defences. Administration of ethanolic neem leaf extract effectively suppressed DMBA-induced HBP carcinogenesis as revealed by the absence of tumours in the initiation phase and reduced tumour incidence in the post-initiation phase. In addition, ethanolic neem leaf extract modulated lipid peroxidation and enhanced antioxidant status in the pouch, liver and erythrocytes and reduced the incidence of bone marrow micronuclei. The results of the present study, demonstrate that ethanolic neem leaf extract inhibits the development of DMBA-induced HBP tumours by protecting against oxidative stress. Copyright © 2004 John Wiley & Sons, Ltd. [source] Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitisCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2001H. J. Lee Background Atopic dermatitis has been seen to result from multifactorial inheritance, with interaction between genetic and environmental factors. The genetic association may differ according to the ethnic backgrounds. Objective The purpose of this study was to investigate the genetic factors in Korean atopic dermatitis patients by studying the human leucocyte antigen (HLA) class I association and polymorphisms of transporters associated with antigen presentation (TAP) and low-molecular-weight polypeptide (LMP) genes. Methods HLA-A and B genotyping was performed in 53 atopic dermatitis patients and 184 healthy controls using the standard microlymphocytotoxicity technique. TAP1, TAP2, LMP2, and LMP7 gene polymorphisms were anaylzed using the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP), PCR-amplification refractory mutation system (ARMS), and PCR-restriction fragment length polymorphism (RFLP). Results Allele frequency of HLA-A24 was significantly increased in patients with atopic dermatitis compared to controls (P < 0.05). HLA-B alleles showed no differences in distribution between patients and controls. Genotype, phenotype, and allele frequencies of TAP1 gene also revealed no differences in distribution between patients and controls. Analysis of TAP2 gene polymorphisms showed increased frequencies of the TAP2*C allele and TAP2*A/TAP2*C genotype in atopic dermatitis patients compared to controls (P < 0.05). Distribution of LMP2 and LMP7 gene polymorphisms was similar for patients and controls. Conclusion This study demonstrates an association of atopic dermatitis with HLA-A24 and TAP2*C alleles in Korean patients. Discrepancy with the previous reports might be related to different patient characteristics and ethnic variations. [source] Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasiaCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007J. Visser Summary Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-,/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-, T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. [source] Side Effects and Complications of Fractional Laser Photothermolysis: Experience with 961 TreatmentsDERMATOLOGIC SURGERY, Issue 3 2008EMMY M. GRABER MD BACKGROUND A novel 1,550-nm erbium-doped laser (Fraxel, Reliant Technologies Inc.) has been shown to be effective in the treatment of photodamaged skin and scars with minimal postoperative recovery; however, studies evaluating its side effects and complication rates have been limited. PURPOSE The purpose was to determine the frequency and range of side effects and complications associated with fractional photothermolysis treatment. METHODS A retrospective evaluation of 961 successive 1,550-nm erbium-doped laser treatments in patients of various skin phototypes (I,V) was conducted in a single center. Side effects and complications of treatment, including time of onset and duration, were identified and tabulated. Patient demographics and laser parameters were also assessed. RESULTS Seventy-three treatments (7.6%) resulted in development of complications. The most frequent complications were acneiform eruptions (1.87%) and herpes simplex virus outbreaks (1.77%). Side effects and complications were equally distributed across different ages, skin types, body locations, laser parameters, and underlying skin conditions, except for postinflammatory hyperpigmentation, which occurred with increased frequency in patients with darker skin phototypes. CONCLUSIONS Fractional laser skin treatment is associated with a relatively low complication rate. Side effects and complications observed in this study were temporary and did not result in long-term or significantly severe sequelae (e.g., scarring). [source] Insulin resistance is not coupled with defective insulin secretion in primary hyperparathyroidismDIABETIC MEDICINE, Issue 10 2009F. Tassone Abstract Aims, An increased frequency of both impaired glucose tolerance and Type 2 diabetes mellitus (DM) has been reported in primary hyperparathyroidism (pHPT), thus we sought to investigate insulin sensitivity and insulin secretion in a large series of pHPT patients. Subjects and methods, One hundred and twenty-two consecutive pHPT patients without known DM were investigated [age (mean ± sd) 59.3 ± 13.6 years, body mass index (BMI) 25.7 ± 4.2 kg/m2; serum calcium 2.8 ± 0.25 mmol/l; PTH 203.2 ± 145.4 ng/l]. Sixty-one control subjects were matched, according to the degree of glucose tolerance, in a 2 : 1 patient:control ratio. Fasting- and oral glucose tolerance test-derived estimates of insulin sensitivity and secretion were determined by means of the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Results, Both the QUICKI and ISI composite were lower in pHPT patients than control subjects (P < 0.03 and P < 0.05, respectively) after adjusting for age, systolic blood pressure and BMI. Conversely, all insulin secretion estimates were significantly increased in pHPT patients than in control subjects (P < 0.04 and P < 0.03, respectively) and after adjusting for age, systolic blood pressure and BMI. Log serum calcium levels were negatively associated with the QUICKI and log ISI composite (R = ,0.30, P = 0.001; R = ,0.23, P = 0.020, respectively) in pHPT patients. Serum calcium levels significantly and independently contributed to impaired insulin sensitivity in multivariate analysis (QUICKI as dependent variable: , = ,0.31, P = 0.004, R2 = 0.15; log ISI composite as dependent variable: , = ,0.29, P = 0.005, R2 = 0.16). Conclusions, Our study confirms a reduction in both basal and stimulated insulin sensitivity in primary hyperparathyroidism, in spite of increased insulin secretion. Moreover, our data show for the first time a significant relationship between hypercalcaemia and insulin sensitivity in this condition. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||