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Group 2 innate lymphoid cells are recruited to the nasal mucosa in patients with aspirin-exacerbated respiratory disease.
Eastman, JJ, Cavagnero, KJ, Deconde, AS, Kim, AS, Karta, MR, Broide, DH, Zuraw, BL, White, AA, Christiansen, SC, Doherty, TA
The Journal of allergy and clinical immunology. 2017;(1):101-108.e3
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Abstract
BACKGROUND Aspirin-exacerbated respiratory disease (AERD) is characterized by tissue eosinophilia and mast cell activation, including abundant production of prostaglandin D2 (PGD2). Group 2 innate lymphoid cells (ILC2s), which promote tissue eosinophilia and mast cell responses, undergo chemotaxis and cytokine production in response to PGD2, but it is unknown whether ILC2s are active in patients with AERD. OBJECTIVE We sought to determine whether ILC2 numbers change in peripheral blood and the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD. METHODS Blood and nasal scrapings were collected at baseline, during reactions, and after completion of ketorolac/aspirin challenge/desensitization in 12 patients with AERD. ILC2s and eosinophils were quantitated by means of flow cytometry. Urine was also collected, and quantification of PGD2 metabolite and leukotriene E4 levels was done by using ELISA. Baseline and nonsteroidal anti-inflammatory drug reaction clinical data were correlated with cell changes. RESULTS ILC2 numbers significantly increased in nasal mucosal samples and decreased in blood at the time of COX-1 inhibitor reactions in 12 patients with AERD. These changes were not observed in 2 patients without AERD. Furthermore, eosinophil numbers decreased in blood concurrently with significant increases in urinary PGD2 metabolite and leukotriene E4 levels. The magnitude of increases in nasal mucosal ILC2 numbers positively correlated with maximum symptom scores during challenges. Furthermore, blood ILC2 numbers during the reaction correlated with time for the reaction to resolve, possibly reflecting reaction severity. CONCLUSIONS ILC2s are recruited to the nasal mucosa during COX-1 inhibitor-induced reactions in patients with AERD, correlating with enhanced production of prostaglandins and leukotrienes.
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Neutrophil-to-lymphocyte ratio in patients with severe tinnitus: prospective, controlled clinical study.
Ozbay, I, Kahraman, C, Balikci, HH, Kucur, C, Kahraman, NK, Ozkaya, DP, Oghan, F
The Journal of laryngology and otology. 2015;(6):544-7
Abstract
OBJECTIVE To determine the relationship between severe tinnitus and inflammation using the neutrophil-to-lymphocyte ratio as a marker of stress. METHODS A total of 107 patients who had been suffering with severe tinnitus (tinnitus handicap inventory scale grades of 3-5) for at least 2 weeks were recruited. Patients underwent detailed ENT examinations and audiometric tests to exclude a relevant pathological cause of the tinnitus. Patients with systemic diseases, malignancy or inflammatory diseases that could alter neutrophil-to-lymphocyte ratio were excluded. A total of 107 age- and sex-matched healthy control participants were also recruited. Routine laboratory test results and neutrophil-to-lymphocyte ratio were compared between the patients and controls. RESULTS Lipid profile, liver function, white blood cell count, haemoglobin level, mean corpuscular volume, and vitamin B12 and folate levels were similar among the patients and controls. However, mean neutrophil-to-lymphocyte ratio was significantly higher among the patients than the controls (p < 0.05). CONCLUSION The findings of this novel study suggest that neutrophil-to-lymphocyte ratio should be considered during the evaluation of tinnitus patients as a potential clinical marker of tinnitus. Further studies are required to verify the findings.
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Impact of spinach consumption on DNA stability in peripheral lymphocytes and on biochemical blood parameters: results of a human intervention trial.
Moser, B, Szekeres, T, Bieglmayer, C, Wagner, KH, Mišík, M, Kundi, M, Zakerska, O, Nersesyan, A, Kager, N, Zahrl, J, et al
European journal of nutrition. 2011;(7):587-94
Abstract
INTRODUCTION A controlled intervention trial was conducted to assess the impact of spinach consumption on DNA stability in lymphocytes and on health-related biochemical parameters. METHODS The participants (n = 8) consumed homogenised spinach (225 g/day/person) over a period of 16 days. DNA migration was monitored in single cell gel electrophoresis-comet assays under standard conditions, which reflect single- and double-strand breaks, after treatment of nuclei with lesion-specific enzymes (formamidopyrimidine glycosylase, FPG and endonuclease III, ENDO III) and after treatment of intact cells with H(2)O(2) before, during and after intervention. RESULTS While no reduction in DNA damage was observed under standard conditions after different time intervals of spinach intake, other endpoints, namely ROS sensitivity and DNA migration attributable to the formation of oxidatively damaged DNA bases (i.e. pyrimidines-ENDO III-sensitive sites and purines-FPG sensitive sites) were reduced 6 h after consumption of the first portion and after 11 days of continuous consumption. In the case of ENDO III-sensitive sites, also after 16 days, a decrease in comet formation was observed. At the end of a 40 days washout period, the DNA stability parameters were not significantly different from the background values. Other biochemical parameters which were significantly altered by spinach intake were the folate (+27%) and homocysteine (-16%) concentrations in blood, and it was found in an earlier human study that folate may prevent oxidative damage to DNA bases. CONCLUSIONS Taken together, our results show that moderate consumption of spinach causes protection against oxidative DNA damage in humans and that this phenomenon is paralleled by alterations of health-related biochemical parameters.
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Does cellular glucose transport respond to a controlled diet and sulfonylurea therapy in type 2 diabetes mellitus?
Tatoń, J, Piatkiewicz, P, Czech, A
Endokrynologia Polska. 2010;(1):75-81
Abstract
INTRODUCTION The normalization of cellular glucose assimilation is the basic aim of therapy in diabetes mellitus. This process should be accompanied by a proportional increase of the cellular glucose transport (CGT). The level of CGT should react to therapy typically recommended in Type 2 diabetes mellitus (T2DM), composed of diet and sulfonylurea. In order to explore this clinically significant hypothesis, a clinical-experimental study was undertaken. Its aim was to determine the clinical pharmacotherapeutic significance of CGT measurements. MATERIAL AND METHODS CGT testing was performed on peripheral blood lymphocytes. CGT was assessed with 2-[(3)H(G)] glucose: before, and after the addition of sulfonylurea or sulfonylurea plus insulin to the incubation medium. Tests were performed at baseline in 28 persons with newly diagnosed, "therapeutically naive" T2DM and in 20 control subjects. In diabetic patients the tests for CGT were repeated after 3 months of routine diet and sulfonylurea therapy. In addition, the level of GLUT4 expression was assessed by flow cytometry before and after this therapy. RESULTS Before treatment, CGT was significantly decreased in all subjects with T2DM. Incubated in-vitro cells responded directly to the addition of sulfonylurea with a moderate increase of CGT. This response was augmented by the addition of insulin to sulfonylurea in the incubation medium. The monitored three-month routine, controlled therapy with diet and sulfonylurea resulted in a significant increase of CGT process in all types of incubation tests. CONCLUSIONS The basal and reactive CGT is significantly decreased in lymphocytes of persons with T2DM before the introduction of therapy. Effective therapy with diet and sulfonylurea normalizes both types of CGT - basal and reactive. It is related to the near normalization of GLUT4 expression in the studied cells. This phenomenon may be used as a new marker for diabetes mellitus pharmacotherapy. (Pol J Endocrinol 2010; 61 (1): 75-81).
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Modulation of nucleotide excision repair in human lymphocytes by genetic and dietary factors.
Langie, SA, Wilms, LC, Hämäläinen, S, Kleinjans, JC, Godschalk, RW, van Schooten, FJ
The British journal of nutrition. 2010;(4):490-501
Abstract
Gene-environment interactions determine inter-individual variations in nucleotide excision repair (NER) capacity. Oxidative stress was previously found to inhibit NER, thus supplementation with dietary antioxidants could prevent this inhibition, especially in genetically susceptible subjects. To study the effects of genetic polymorphisms in NER-related genes and dietary intake of antioxidants on an individual's NER capacity, lymphocytes of 168 subjects were isolated before and after a 4-week blueberry and apple juice intervention. Twelve genetic polymorphisms in NER genes XPA, XPC, ERCC1, ERCC2, ERCC5, ERCC6 and RAD23B were assessed by multiplex PCR with single base extension. Based on specific genotype combinations, a subset of individuals (n 36) was selected for phenotypical assessment of NER capacity, which was significantly affected by the total sum of low-activity alleles (P = 0.027). The single polymorphism XPA G23A was the strongest predictor of NER capacity (P = 0.002); carriers of low-activity alleles AA had about three times lower NER capacity than XPA GG carriers. NER capacity assessed before and after intervention correlated significantly (R(2) 0.69; P < 0.001), indicating that inter-individual differences in NER capacity are maintained over 4 weeks. Although the intervention increased plasma trolox equivalent antioxidant capacity from 791 (SE 6.61) to 805 (SE 7.90) microm (P = 0.032), on average it did not affect NER capacity. Nonetheless, carriers of twelve or more low-activity alleles seemed to benefit from the intervention (P = 0.013). Among these, carriers of the variant allele for RAD23B Ala249Val showed improved NER capacity upon intervention (P = 0.020). In conclusion, improved NER capacity upon dietary intervention was detected in individuals carrying multiple low-activity alleles. The XPA G23A polymorphism might be a predictor for NER capacity.
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The effects of intensive, moderate and downhill treadmill running on human blood lymphocytes expressing the adhesion/activation molecules CD54 (ICAM-1), CD18 (beta2 integrin) and CD53.
Simpson, RJ, Florida-James, GD, Whyte, GP, Guy, K
European journal of applied physiology. 2006;(1):109-21
Abstract
This study examined the effects of intensive, moderate and downhill treadmill running on blood lymphocyte expression of adhesion/activation (AA) molecules. Trained subjects completed three treadmill-running protocols of identical duration: (1) an intensive protocol at 80% VO2max to volitional exhaustion, (2) a moderate protocol at 60% VO2max and (3) a -10% downhill (eccentric) protocol at 80% VO2max. Blood samples were taken before, immediately after, 1 and 24 h after exercise. Isolated lymphocytes were assessed for expression of the AA molecules CD54, CD18 and CD53 by flow cytometry. Lymphocyte counts increased immediately after all running protocols. Lymphocytopenia was observed 1 h after the intensive and eccentric protocols only. Plasma creatine kinase increased 24 h after the downhill protocol only. Increases in the number and percentage of CD54+, CD18bright and CD53bright lymphocytes were observed immediately after the intensive and eccentric protocols, with the numbers falling below pre-exercise values at 1 h post-exercise for all protocols. No differences were found between the intensive protocol and the eccentric protocol at the same relative intensity. Analysis of lymphocyte subsets showed that the total number of CD3+, CD4+, CD8+ and CD56+ lymphocytes increased after the intensive protocol before falling below pre-exercise values at 1 h post-exercise. A relatively greater mobilisation of CD56+ and CD8+ cells accounts for the changes in CD54+, CD18bright and CD53bright cell populations. Lymphocytes that enter and exit the circulation following exercise express high levels of AA molecules, which may mediate extravasation and post-exercise lymphocytopenia. This effect appears to be influenced by exercise intensity and not muscle damage.
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alpha-Tocopherol as an antiretroviral therapy supplement for HIV-1-infected patients for increased lymphocyte viability.
de Souza Júnior, O, Treitinger, A, Baggio, GL, Michelon, C, Verdi, JC, Cunha, J, Ferreira, SI, Spada, C
Clinical chemistry and laboratory medicine. 2005;(4):376-82
Abstract
The aim of our study was to evaluate the benefits of supplementation with 800 mg/day of alpha-tocopherol with regard to cellular viability in HIV-1 seropositive patients undergoing anti-retroviral therapy. A total of 29 patients participated in the study, of whom 14 were given the supplement and 15 a placebo. The analyses were carried out before treatment commenced and after 60, 120 and 180 days. The plasma levels of HIV-1 RNA showed a significant decrease as a consequence of treatment time in the groups studied (p = 0.0001), although the difference between the treatments over time was not verified (p = 0.7343). The percentage of viable lymphocytes showed a significant increase as a consequence of treatment time in both groups studied (p = 0.0002) and a significant difference between the treatments over time (p = 0.0472). The percentage of lymphocytes in apoptosis showed a significant reduction over time (p = 0.0003), as well as a significant difference between the treatments over time (p = 0.0321). The significant increase in cellular viability indicates that supplementation with alpha-tocopherol offers an additional positive effect on cellular preservation in HIV-1 individuals undergoing anti-retroviral therapy; however, it represents an additional risk of anti-retroviral therapeutic failure, possibly due to drug-drug interaction involving up-regulation of metabolic clearance.
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Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection.
Porrini, M, Riso, P, Brusamolino, A, Berti, C, Guarnieri, S, Visioli, F
The British journal of nutrition. 2005;(1):93-9
Abstract
The salutary characteristics of the tomato are normally related to its content of carotenoids, especially lycopene, and other antioxidants. Our purpose was to verify whether the daily intake of a beverage prototype called Lyc-o-Mato((R)) containing a natural tomato extract (Lyc-o-Mato((R)) oleoresin 6 %) was able to modify plasma and lymphocyte carotenoid concentrations, particularly those of lycopene, phytoene, phytofluene and beta-carotene, and to evaluate whether this intake was sufficient to improve protection against DNA damage in lymphocytes. In a double-blind, cross-over study, twenty-six healthy subjects consumed 250 ml of the drink daily, providing about 6 mg lycopene, 4 mg phytoene, 3 mg phytofluene, 1 mg beta-carotene and 1.8 mg alpha-tocopherol, or a placebo drink. Treatments were separated by a wash-out period. Plasma and lymphocyte carotenoid and alpha-tocopherol concentrations were determined by HPLC, and DNA damage by the comet assay. After 26 d of consumption of the drink, plasma carotenoid levels increased significantly: concentrations of lycopene were 1.7-fold higher (P<0.0001); of phytofluene were 1.6-fold higher (P<0.0001); of phytoene were doubled (P<0.0005); of beta-carotene were 1.3-fold higher (P<0.05). Lymphocyte carotenoid concentrations also increased significantly: that of lycopene doubled (P<0.001); that of phytofluene was 1.8-fold higher (P<0.005); that of phytoene was 2.6-fold higher (P<0.005); that of beta-carotene was 1.5-fold higher (P<0.01). In contrast, the alpha-tocopherol concentration remained nearly constant. The intake of the tomato drink significantly reduced (by about 42 %) DNA damage (P<0.0001) in lymphocytes subjected to oxidative stress. In conclusion, the present study supports the fact that a low intake of carotenoids from tomato products improves cell antioxidant protection.
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Evidence of increased chromosomal abnormalities in French Polynesian thyroid cancer patients.
Violot, D, M'Kacher, R, Adjadj, E, Dossou, J, de Vathaire, F, Parmentier, C
European journal of nuclear medicine and molecular imaging. 2005;(2):174-9
Abstract
PURPOSE The aim of this study was to evaluate the frequency of chromosomal abnormalities in thyroid cancer patients before and after radioactive iodine administration in order to assess cytogenetic particularity in Polynesian thyroid cancer patients. METHODS Chromosomal abnormalities were studied in 30 Polynesian patients with differentiated thyroid cancer, prior to and 4 days after 131I administration. Unstable chromosomal abnormalities were counted in peripheral blood lymphocytes using a conventional cytogenetic method. Peripheral blood was irradiated in vitro at different doses (0.5, 1 and 2 Gy) in order to establish the dose-response of the lymphocytes. Control groups were composed of 50 European thyroid cancer patients before and after first administration of 131I, and of ten European healthy donors. In addition, in vitro irradiation assays were performed at different doses (0.5, 1 and 2 Gy). RESULTS The relative risk of spontaneous dicentrics before any radiation treatment was 2.9 (95% CI 1.7-5.1) times higher among Polynesian thyroid patients than among European thyroid cancer patients. After in vitro irradiation, the rise in frequency of dicentrics was similar in the Polynesian thyroid cancer group and the European thyroid patients and healthy donors. Four days after administration of 3.7 GBq 131I, the relative risk for a dicentric per cell was 1.3 (95% CI 1.0-1.5) times higher in Polynesian than in European patients. This can be explained by higher 131I retention in Polynesian compared with European patients. The results obtained revealed an increased frequency of cytogenetic abnormalities in Polynesian thyroid cancer patients compared with European control patients. CONCLUSION These preliminary findings are compatible with possible previous environmental aggression and therefore imply a need for further investigations on larger series including, in particular, French Polynesian healthy donors. In addition to French Polynesians, Maori and Hawaiian control groups could be useful.
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Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response.
Utter, GH, Owings, JT, Lee, TH, Paglieroni, TG, Reed, WF, Gosselin, RC, Holland, PV, Busch, MP
The Journal of trauma. 2005;(5):925-31; discussion 931-2
Abstract
BACKGROUND Blood transfusion can result in long-term survival of donor leukocyte subpopulations, or microchimerism, in the peripheral blood of injured patients. Neither injury severity nor the number of transfusions is associated with its occurrence. We sought to determine whether changes in general or antigen-specific lymphocyte activation may be associated with the subsequent development of microchimerism. METHODS We evaluated 63 transfused trauma patients, which we compared with 10 non-transfused trauma patients and 10 healthy control subjects. Of the 63 transfused patients, 31 were known to have evidence of microchimerism at hospital discharge with real-time quantitative PCR for non-recipient HLA DR alleles. We assessed lymphocyte response to phytohemagglutinin (PHA) using blood sampled upon arrival to the hospital (before transfusion) and at discharge. We performed one-way mixed leukocyte cultures (MLC) with pre-transfusion recipient specimens to assess recipient lymphocyte response to mitomycin-C treated donor cells and vice versa. RESULTS Lymphocyte response to PHA in microchimeric transfusion recipients was lower at admission (before transfusion) and discharge than in non-microchimeric recipients. Lymphocytes from microchimeric patients had less response to donor cells than did lymphocytes from non-microchimeric patients. Microchimeric patients also more frequently had diminished lymphocyte response to a single blood donor on MLC. CONCLUSIONS Transfusion-associated microchimerism is correlated with diminished response to mitogen challenge as well as to specific alloantigenic challenges. This microchimerism is predated by diminished lymphocyte response to a specific blood donor in many instances. The blood donor associated with this diminished alloantigenic lymphocyte response may be the source of microchimeric cells present in the recipient.