Increased radiosensitivity of a subpopulation of T-lymphocyte progenitors from patients with Fanconi's anemia

International Nuclear Information System (INIS)

Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.; Rosenblatt, L.S.; Reeves, J.D.; Misra, H.

1981-01-01

In vitro radiation survival of peripheral blood T lymphocytes was studied in 15 clinically normal adults and 4 patients with Fanconi's anemia. Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and a newly developed whole blood T-lymphocyte colony assay were used to measure lymphocyte blastogenesis and colony formation in response to phytohemagglutinin (PHA) or concanavalin-A (Con-A) stimulation. Lymphocyte colony formation was found to be consistently more sensitive than the LST for detection of low-level radiation effects using both normal cells and lymphocytes from Fanconi's anemia patients. Lymphocytes from patients with Fanconi's anemia were significantly more sensitive to in vitro x irradiation than lymphocytes from clinically normal individuals as measured by their ability to divide when stimulated by PHA in the LST and colony formation assay. No significant difference in the radiosensitivity of the Con-A response was observed between the two groups. The PHA-responsive T-lymphocyte subpopulation in Fanconi's anemia patients appears to be intrinsically defective. The nature of this defect, significance in the disease process, and relevancy of these findings to the establishment of radiation protection standards are discussed

Lymphocytic Colitis: Pathologic predictors of response to therapy.

Science.gov (United States)

Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

2018-02-13

While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

DEFF Research Database (Denmark)

Ellingsen, A R; Sørensen, F B; Larsen, Jytte Overgaard

2001-01-01

with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared......Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin...... with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically...

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

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Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

2012-01-01

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia

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Herman, S E M; Niemann, C U; Farooqui, M

2014-01-01

Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...... investigation. Here we report correlative studies in 64 patients with CLL treated with ibrutinib. We quantified tumor burden in blood, lymph nodes (LNs), spleen and bone marrow, assessed phenotypic changes of circulating cells and measured whole-blood viscosity. With just one dose of ibrutinib, the average...

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

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Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

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Wang D

2013-03-01

Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

Pattern of CD4 T‑lymphocyte Values in Cancer Patients on Cytotoxic ...

African Journals Online (AJOL)

Background: Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated ...

Short-term effects of regional irradiation on lymphocytes, T lymphocytes and eosinophils

International Nuclear Information System (INIS)

Chazarin, C.; Roche, H.; Bugat, R.; Pris, F.

1983-01-01

Twenty-three cancer patients treated only by regional irradiation were studied. Radiotherapy was delivered to the pelvis in 14 patients and to the mediastinum in 9. T lymphocytes were evaluated with the Jondal technique. Before treatment, lymphocyte counts were identical in patients and control. Decreases in total lymphocytes and T lymphocytes became significant in both groups after 40 Gy. Significant rises in eosinophil counts were found only after abdominal irradiation and seemed unrelated to variations in lymphocyte counts [fr

The determination of lymphocyte transformation in patients of various diseases

International Nuclear Information System (INIS)

Su Liaoyuan; Liu Ke Liang; Lin Xingcheng; Sun Guoqi; Xue Zhimou

1987-01-01

The synthesis of DNA, RNA and protein during the transformation of human lymphocytes induced by mitogen PHA and LPS was investigated by quantitation of 3 H-TdR, 14 C-UR and 14 C-valine incorporation method. 1666 tests were carried out in patients with various diseases and 424 tests in normal subjects. It was found that immunocompetence was closely related with the progress and prognosis in patients with leukemia. Impairment of the cell-mediated immunity in patients with squamous cell carcinoma and with encephlitis was observed. There was no difference in immunity between patients with adenocarcinoma and the normal subjects. The ionizing irradiation mainly exerts its effect on cell-mediated immunity. The cell-mediated immunity was found to be impaired while the humoral immune regulation was enhanced in tuberculosis and leprosy, indicating that these diseases were caused by impairment of cell-mediated immunity. Both humoral and cell-mediated immunity return to normal levels at convalescence. The uptake of 14 C-UR by lymphocytes in patients with hepatitis increased significantly. Lymphocytes reactivity was elevated in patients with vernal conjunctivities and normal in patients with uveitis. Low reactivity was observed in patients with keratitis. The immunity in various diseases was discussed

Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes

International Nuclear Information System (INIS)

Lucas, J.N.; Hill, F.; Burk, C.; Straume, T.; Swansbury, G.; Clutterbuck, R.

1994-01-01

The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukaemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure pre-cancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of ∼ 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer in such patients. (Author)

Radioiodine-induced changes in lymphocyte subsets in patients with differentiated thyroid carcinoma

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Tofani, A.; Sciuto, R.; Cioffi, R.P.; Pasqualoni, R.; Rea, S.; Festa, A.; Maini, C.L. [Department of Nuclear Medicine, Regina Elena Cancer Institute, Rome (Italy); Gandolfo, G.M.; Arista, M.C. [Department of Clinical Pathology, Regina Elena Cancer Institute, Rome (Italy)

1999-08-01

This study evaluated changes in lymphocyte subsets in patients with thyroid carcinoma who received iodine-131 for diagnostic and therapeutic purposes. Twenty thyroid cancer patients were entered in the study after total thyroidectomy: ten patients (group A) underwent whole-body scintigraphy with 185 MBq of {sup 131}I and the other ten (group B) received 3700 MBq of {sup 131}I therapy. All patients were in a hypothyroid state at the time of administration of {sup 131}I and started l-thyroxine 150 {mu}g/day 3 days after {sup 131}I administration. Free and bound triiodothyronine and thyroxine, thyroid-stimulating hormone, thyroglobulin, thyroglobulin antibodies, thyroid peroxidase/microsomal antibodies, white blood cell, lymphocyte counts and lymphocyte subsets were serially determined at baseline and at days 2, 7, 15, 30 and 60 after {sup 131}I administration. Twenty healthy age- and sex-matched individuals were used as a reference population for lymphocyte subset values. In group A only a reduction in NK cells at days 7 (P=0.043) and 15 (P=0.037) was observed. In group B, patients showed a delayed reduction in the total lymphocyte count at days 15, 30 and 60 (P=0.008, 0.004 and 0.018, respectively), and a decrease in B cells throughout the study (at days 7, 15, 30 and 60: P=0.006, 0.0017, 0.0017 and 0.0017 respectively). A transient decrease in NK cells was observed at days 15 (P=0.025) and 30 (P=0.008). Among T cells, the helper phenotype (CD4+) was mainly affected, resulting in a reduction in the CD4+/CD8+ ratio at day 60 (P=0.046). Comparing the two groups, the numbers of B lymphocytes at day 30 (P=0.023) and NK cells at days 2 (P=0.037) and 30 (P=0.023) were significantly lower in group B. Neither group showed any clinical sign of immunosuppression during the follow-up period. In patients with thyroid cancer the sensitivity of lymphocytes to the effects of {sup 131}I administered for diagnostic or therapeutic purposes depends upon lymphocyte phenotype and {sup

DNA repair deficiency in lymphocytes from patients with actinic keratosis

International Nuclear Information System (INIS)

Abo-Darub, J.M.; Mackie, R.; Pitts, J.D.

1978-01-01

DNA repair activity was measured in peripheral blood lymphocytes from 18 patients with Actinic Keratosis and 18 age-matched control subjects, by comparing the incorporation of 3 H-thymidine into cells after irradiation with ultraviolet light with that into unirradiated cells. The incorporation was followed autoradiographically or by measuring acid insoluble radioactivity in cells labelled in the presence of hydroxyurea. The repair activity in lymphocytes from Actinic keratosis patients was only 47.1% (+-6.5%) of that in cells from the control subjects

Lymphocyte aggregates persist and accumulate in the lungs of patients with idiopathic pulmonary fibrosis

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Todd NW

2013-03-01

Full Text Available Nevins W Todd,1,2 Rachel G Scheraga,1,3 Jeffrey R Galvin,1,4 Aldo T Iacono,1 E James Britt,1 Irina G Luzina,1,2 Allen P Burke,5,* Sergei P Atamas1,2,* 1Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA; 2Baltimore VA Medical Center, Baltimore, MD, USA; 3Critical Care Medicine Department, National Institutes of Health, Bethesda, MD, USA; 4Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, MD, USA; 5Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA *These authors contributed equally to this work Background: Idiopathic pulmonary fibrosis (IPF is a fatal lung disease with no known effective therapy. It is often assumed, but has not been objectively evaluated, that pulmonary inflammation subsides as IPF progresses. The goal of this work was to assess changes in the degree of inflammatory cell infiltration, particularly lymphocytic infiltration, over the duration of illness in IPF. Methods: Sixteen patients with confirmed IPF were identified in patients whom surgical lung biopsy (SLB was performed in early disease, and in patients whom lung transplantation was subsequently performed in end stage disease. A numerical scoring system was used to histologically quantify the amount of fibrosis, honeycomb change, fibroblastic foci, and lymphocyte aggregates in each SLB and lung explant tissue sample. Analyses of quantitative scores were performed by comparing paired, matched samples of SLB to lung explant tissue. Results: Median time [1st, 3rd quartiles] from SLB to lung transplantation was 24 [15, 29] months. Histologic fibrosis and honeycomb change were more pronounced in the explant samples compared with SLB (P < 0.001 and P < 0.01, respectively, and most notably, higher numbers of lymphocyte aggregates were observed in the explant samples compared to SLB (P = 0.013. Immunohistochemical analyses revealed abundant CD3+ (T lymphocyte and CD20+ (B

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial.

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O'Brien, Susan; Furman, Richard R; Coutre, Steven E; Sharman, Jeff P; Burger, Jan A; Blum, Kristie A; Grant, Barbara; Richards, Donald A; Coleman, Morton; Wierda, William G; Jones, Jeffrey A; Zhao, Weiqiang; Heerema, Nyla A; Johnson, Amy J; Izumi, Raquel; Hamdy, Ahmed; Chang, Betty Y; Graef, Thorsten; Clow, Fong; Buggy, Joseph J; James, Danelle F; Byrd, John C

2014-01-01

Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65-84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1-2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one

MicroRNA expression profiling identifies activated B cell status in chronic lymphocytic leukemia cells.

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Shuqiang Li

2011-03-01

Full Text Available Chronic lymphocytic leukemia (CLL is thought to be a disease of resting lymphocytes. However, recent data suggest that CLL cells may more closely resemble activated B cells. Using microRNA (miRNA expression profiling of highly-enriched CLL cells from 38 patients and 9 untransformed B cells from normal donors before acute CpG activation and 5 matched B cells after acute CpG activation, we demonstrate an activated B cell status for CLL. Gene set enrichment analysis (GSEA identified statistically-significant similarities in miRNA expression between activated B cells and CLL cells including upregulation of miR-34a, miR-155, and miR-342-3p and downregulation of miR-103, miR-181a and miR-181b. Additionally, decreased levels of two CLL signature miRNAs miR-29c and miR-223 are associated with ZAP70(+ and IgV(H unmutated status and with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the direction of change of individual miRNAs may predict clinical course in CLL.

Tumor-infiltrating lymphocytes (TILs) from patients with glioma

DEFF Research Database (Denmark)

Liu, Zhenjiang; Meng, Qingda; Bartek, Jiri

2017-01-01

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21...

Subpopulation of lymphocytes in patients with cancer of the head and neck

International Nuclear Information System (INIS)

Yoshida, Atsuhiro; Tomita, Kinai; Toda, Norikazu; Sekine, Kiyoshi; Mizugoe, Takanori

1978-01-01

On 31 patients with cancer of the head and neck, lymphocyte count and T- and B-cell levels were determined, and their changes following radiotherapy and the effect of picibanil on their changes were examined. 1) Lymphocyte count and T-cell count decreased remarkably following radiotherapy. B-cell count changed a little. Changes in lymphocyte count seemed chiefly to be due to changes in T-cell. 2) At 3 weeks after radiotherapy, lymphocyte count and T-cell count remained to be low in the patients who were not given picibanil, but those counts tended to increase in the patients who were given picibanil. The effect of picibanil was statistically significant in the experienced cases except those of maxillary cancer. 3) At 3 weeks after radiotherapy, T-cell count was significantly low in those who were not given picibanil and had unfavourable prognosis. 4) With 5 times repeated intramuscular injections of picibanil (0.2 KE), T-cell % and T-cell count increased in some cases. (Ueda, J.)

Increased ratio between anaerobic and aerobic metabolism in lymphocytes from hyperthyroid patients.

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Valdemarsson, S; Monti, M

1994-03-01

While an increased oxygen consumption is accepted as one consequence of hyperthyroidism, only few data are available on the role of anaerobic processes for the increased metabolic activity in this disease. In this study we evaluated the relative importance of anaerobic and aerobic metabolism for the metabolic activity in lymphocytes from patients before and after treatment for hyperthyroidism. Total lymphocyte heat production rate (P), reflecting total cell metabolic activity, was determined in a plasma lymphocyte suspension using direct microcalorimetry. The contribution from aerobic metabolism (O2-P) was calculated from the product of the lymphocyte oxygen consumption rate and the enthalpy change for glucose combustion, and the anaerobic contribution as the difference between P and O2-P. The total lymphocyte heat production rate P was 3.37 +/- 0.25 (SEM) pW/cell (N = 11) before and 2.50 +/- 0.11 pW/cell (N = 10) after treatment for hyperthyroidism (p hyperthyroid state and to 73.7 +/- 3.2% after treatment (p metabolic activity demonstrated in lymphocytes from hyperthyroid patients cannot be explained by an increased oxygen-dependent consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

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Jayesh H. Prajapati

2014-01-01

Full Text Available Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR and neutrophil-lymphocyte ratio (NLR with high density lipoprotein (HDL cholesterol levels in coronary artery disease (CAD patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P=0.008 and NLR (P=0.009; however no significant relationship was obtained with HDL and isolated platelet (P=0.488, neutrophil (P=0.407, and lymphocyte (P=0.952 counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024 and NLR (P=0.03 were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P=0.01 and NLR (6.33 versus 5.10; P=0.01 were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007 and NLR (P=0.001 were inversely associated with HDL, whereas in older population only NLR (P=0.05 had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

To the nucleolar bodies (nucleoli) in cells of the lymphocytic lineage in patients suffering from B - chronic lymphocytic leukemia.

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Smetana, K; Karban, J; Trneny, M

2010-01-01

The present study was undertaken to provide more information on nucleoli in lymphocytes of B - chronic lymphocytic leukemia. The computer assisted nucleolar and cytoplasmic RNA image densitometry, reflecting the nucleolar and cytoplasmic RNA concentration at the single cell level, demonstrated a remarkable stability during the differentiation and maturation of B- lymphocytes. In contrast, as it was expected, the nucleolar diameter during the lymphocytic development markedly decreased. Thus the nucleolar RNA content of leukemic B-lymphocytes was apparently related to the nucleolar size. In both immature and mature lymphocytes, the cytostatic treatment increased the incidence of micronucleoli, which represent the "inactive" type of nucleoli. However, the decreased values of the nucleolar diameter were statistically significant only in mature lymphocytes of treated patients. On the other hand, despite such observation, it must be mentioned that "large active" and "ring shaped resting" nucleoli were still present in immature and mature lymphocytes after the cytostatic therapy and such cells might represent a potential pool of proliferating cells. As it is generally accepted "large active nucleoli" with multiple fibrillar centers are known to be characteristic for proliferating cells. "Ring shaped resting nucleoli" are present in sleeping cells, which may be stimulated to return to the cell cycle and to proliferate again. In addition, the nucleolar RNA distribution also indicated that Gumprecht ghosts mostly originated from mature lymphocytes. Increased ratio of the nucleolar to cytoplasmic RNA density in Gumprecht ghosts or apoptotic cells and apoptotic bodies of the lymphocytic origin was related to the decreased cytoplasmic RNA concentration. The increased nucleolar size together with the markedly decreased cytoplasmic RNA concentration characteristic for Gumprecht ghosts just reflected the spreading of lymphocytes during smear preparations. In apoptotic cells or

GATA-3 EXPRESSION IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH BRONCHIAL ASTHMA

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V. N. Mineev

2010-01-01

Full Text Available The aim of the study is to establish the features of expression of GATA-3 in peripheral lymphocytes from bronchial asthma patients (BA. Material and methods. 10 healthy controls, 15 patients with allergic (atopic and 15 persons with non-allergic BA were examined. A transcription factor GATA-3 expressed in peripheral lymphocytes was analyzed by Western blot after the lymphocytes were lysed. Preparation of cell lysates, and Western blotting were performed by means of a standard procedure (Amersham. An antibody against GATA-3 (Abcam, UK was used. Levels of the protein were analyzed versus β-actin levels using anti-actin antibody (Sigma Aldrich, USA. Results. Expression of GATA-3 was significantly increased in lymphocytes of patients with allergic BA as compared to healthy persons and non-allergic BA patients. The level of GATA-3 negatively correlated with the degree of airflow obstruction and positively correlated with dosage of parenteral steroids administered. Conclusion. GATA-3 may play a key role in the pathophysiology of BA. One may suggest that increased expression of GATA-3 transcription factor in atopic BA underlie high levels of Th2-cytokines production in allergic disease

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

Science.gov (United States)

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID

Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia

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Ghiotto, Fabio; Fais, Franco; Valetto, Angelo; Albesiano, Emilia; Hashimoto, Shiori; Dono, Mariella; Ikematsu, Hideyuki; Allen, Steven L.; Kolitz, Jonathan; Rai, Kanti R.; Nardini, Marco; Tramontano, Anna; Ferrarini, Manlio; Chiorazzi, Nicholas

2004-01-01

Studies of B cell antigen receptors (BCRs) expressed by leukemic lymphocytes from patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that B lymphocytes with some level of BCR structural restriction become transformed. While analyzing rearranged VHDJH and VLJL genes of 25 non–IgM-producing B-CLL cases, we found five IgG+ cases that display strikingly similar BCRs (use of the same H- and L-chain V gene segments with unique, shared heavy chain third complementarity-determining region [HCDR3] and light chain third complementarity-determining region [LCDR3] motifs). These H- and L-chain characteristics were not identified in other B-CLL cases or in normal B lymphocytes whose sequences are available in the public databases. Three-dimensional modeling studies suggest that these BCRs could bind the same antigenic epitope. The structural features of the B-CLL BCRs resemble those of mAb’s reactive with carbohydrate determinants of bacterial capsules or viral coats and with certain autoantigens. These findings suggest that the B lymphocytes that gave rise to these IgG+ B-CLL cells were selected for this unique BCR structure. This selection could have occurred because the precursors of the B-CLL cells were chosen for their antigen-binding capabilities by antigen(s) of restricted nature and structure, or because the precursors derived from a B cell subpopulation with limited BCR heterogeneity, or both. PMID:15057307

Radiation induced chromosomal instability in lymphocytes of cancer patients

International Nuclear Information System (INIS)

Sudo, H.; Sagara, M.; Ban, S.; Noda, S.; Iwakawa, M.; Harada, Y.; Imai, T.; Cologne, J.B.

2003-01-01

Full text: Cytokinesis-blocked micronucleus (CBMN) assay has been extensively used to evaluate the radiation sensitivity of human individuals. Using the CBMN assay, Scott et al (1998, 1999) demonstrated that a fraction of radiosensitive individuals in breast cancer case population was larger than in normal individual population. However, Vral et al were very skeptical about the Scott et al's findings (2002). Under the approval from the ethical committee of NIRS, peripheral blood was obtained from 46 normal healthy females, 131 breast cancer patients, 32 cervical cancer patients and 7 female head and neck cancer patients. Radiosensitivity of T-lymphocytes was assessed by using a CBMN assay. The frequencies of MN per binucleated cell in healthy donors were 0.031(±0.010) and 0.151(±0.066) for cells treated before and after X-ray-irradiation (2Gy), respectively. Spontaneous MN frequencies in cancer patients were significantly higher than healthy donors (p < 0.001). Radiation sensitivities of breast- and head and neck-cancer patients were significantly higher than normal individuals (p < 0.001). Cervical cancer patients were more resistant to irradiation than healthy donors, though the number of cases for statistical analysis was small. (p < 0.001). We are considering that the HPV infection affected the radiosensitivity of cervical cancer cases. Because it is widely believed that one key mechanism which leads to spontaneous micronucleus formation involves an imbalance of chromosomal segregation and a chromosomal instability in patients' lymphocytes might be greater than that in normal individuals' lymphocytes. Recently, Kuschel et al (2002) demonstrated that ratios in two SNPs on XRCC3 were significantly different between cancer patients and healthy females. Then, we can suppose that the radiation-related genes with low penetrance may be involved in tumorigenesis of mammary- and head and neck-cells, and also, in patients' radiation susceptibility

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

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P.A. Nascimento

2001-02-01

Full Text Available Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the dose-response curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.

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Burger, Jan A; Tedeschi, Alessandra; Barr, Paul M; Robak, Tadeusz; Owen, Carolyn; Ghia, Paolo; Bairey, Osnat; Hillmen, Peter; Bartlett, Nancy L; Li, Jianyong; Simpson, David; Grosicki, Sebastian; Devereux, Stephen; McCarthy, Helen; Coutre, Steven; Quach, Hang; Gaidano, Gianluca; Maslyak, Zvenyslava; Stevens, Don A; Janssens, Ann; Offner, Fritz; Mayer, Jiří; O'Dwyer, Michael; Hellmann, Andrzej; Schuh, Anna; Siddiqi, Tanya; Polliack, Aaron; Tam, Constantine S; Suri, Deepali; Cheng, Mei; Clow, Fong; Styles, Lori; James, Danelle F; Kipps, Thomas J

2015-12-17

Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; PIbrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P=0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, Pibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall

Lymphocyte integrin expression differences between SIRS and sepsis patients.

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Heffernan, D S; Monaghan, S F; Ayala, Alfred

2017-11-01

Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

Energy Technology Data Exchange (ETDEWEB)

Khandogina, E K; Mutovin, G R; Filyushkin, I V; Akif' ev, A P

1980-02-01

The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during ..gamma..-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source /sup 60/Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed.

Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

International Nuclear Information System (INIS)

Khandogina, E.K.; Mutovin, G.R.; Filyushkin, I.V.; Akif'ev, A.P.

1980-01-01

The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during γ-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source 60 Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed

Length of hospitalization is associated with selected biomarkers (albumin and lymphocytes) and with co-morbidities: study on 4000 patients.

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Pontiroli, Antonio E; Loreggian, Lara; Rovati, Marco P L; De Patto, Elena; Folini, Laura; Raveglia, Federico; De Simone, Matilde; Baisi, Alessandro; Cioffi, Ugo

2017-01-01

Low albumin levels and low lymphocyte counts are intra hospital conditions that exert a negative influence on prognosis, healing and length of hospitalization. The study aimed to analyze the correlation between low blood levels of albumin, low lymphocytes, and length of stay. The secondary aim was to identify other co-morbidities associated with prolonged hospital stay. Retrospective pilot study was conducted by analyzing anamnestic and biochemical data, related to 4038 patients admitted to ten wards of Hospital San Paolo (Milan), collected from July 1 st 2012 to December 31 st 2012. A statistical analysis was carried out using the Correlation method, Multivariate Analysis and Regression. Lymphocyte count and co-morbidities were evaluated in the whole cohort, albumin levels in 1437 patients. In the whole sample, low albumin levels and low lymphocyte counts were directly correlated to longer hospitalizations. The stratification of the results by department and diagnosis suggests that there is a higher correlation in certain subpopulations, and albumin shows a greater correlation with length of stay than lymphocytes. Also advanced age, high platelets, type of diagnosis, male gender and emergency admission led to longer hospitalizations. A routine check of albumin, lymphocytes and a spectrum of significant variables can provide precious information which can eventually lead to a shorter hospital stay. Knowledge of the general health status of a patient and the possibility to estimate his/her length of hospital stay are essential information for Clinical Governance, and for the improvement of internal services of hospitals on a large scale.

Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis.

Science.gov (United States)

Tsujimura, Shizuyo; Saito, Kazuyoshi; Nakayamada, Shingo; Tanaka, Yoshiya

2010-04-01

P-glycoprotein (P-gp) on activated lymphocytes is an adenosine triphosphate (ATP)-binding cassette transporter that causes drug resistance by exclusion of intracellular drugs in patients with active rheumatoid arthritis (RA). However, infliximab with methotrexate (MTX) can overcome P-gp-mediated drug resistance. We encounter patients who cannot continue infliximab or MTX. Here we tested how etanercept affected P-gp-mediated drug resistance in such intractable RA patients. Peripheral lymphocytes of 11 RA patients (3 switched from infliximab and 8 who could not be treated with MTX) were analyzed for P-gp expression by flow cytometry and for drug exclusion using radioisotope-labeled dexamethasone. Activated lymphocytes of RA patients overexpressed P-gp and coexpressed CD69. Incubation of these lymphocytes with dexamethasone in vitro reduced intracellular dexamethasone levels. Two-week etanercept therapy significantly reduced P-gp expression and eliminated such P-gp- and CD69-high-expressing subgroup. The reduction in P-gp resulted in recovery of intracellular dexamethasone levels in lymphocytes and improvement of disease activity, thus allowing tapering of corticosteroids. None of the patients experienced any severe adverse effects. Etanercept is useful for overcoming P-gp-mediated treatment resistance in intractable RA patients who have to discontinue infliximab or are intolerant to MTX.

Is combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma?

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Tanoglu A

2014-03-01

Full Text Available Alpaslan Tanoglu,1 Ergenekon Karagoz,2 Nurettin Yiyit,3 Ufuk Berber4 1Department of Gastroenterology, 2Department of Infectious Diseases and Clinical Microbiology, 3Department of Thoracic Surgery, 4Department of Pathology, GATA Haydarpasa Training Hospital, Uskudar, TurkeyWe read with interest the recent article entitled "Combination of neutrophil to lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma" by Feng et al.1 In their study, authors aimed to investigate the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Finally, they concluded that combination of NLR and PLR is a useful predictor of postoperative survival in patients with ESCC and combination of these parameters is superior to NLR or PLR as a predictive factor in patients with ESCC. We would like to thank the authors for their contribution.View original paper by Feng and colleagues.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

DEFF Research Database (Denmark)

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated t......Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator......-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months...... 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not...

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

Science.gov (United States)

He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

2018-02-01

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

Exercise Training positively modulates the Ectonucleotidase Enzymes in Lymphocytes of Metabolic Syndrome Patients.

Science.gov (United States)

Martins, C C; Bagatini, M D; Cardoso, A M; Zanini, D; Abdalla, F H; Baldissarelli, J; Dalenogare, D P; Dos Santos, D L; Schetinger, M R C; Morsch, V M M

2016-11-01

In this study, we investigated the cardiovascular risk factors as well as ectonucleotidase activities in lymphocytes of metabolic syndrome (MetS) patients before and after an exercise intervention. 20 MetS patients, who performed regular concurrent exercise training for 30 weeks, 3 times/week, were studied. Anthropometric, biochemical, inflammatory and hepatic parameters and hydrolysis of adenine nucleotides and nucleoside in lymphocytes were collected from patients before and after 15 and 30 weeks of the exercise intervention as well as from participants of the control group. An increase in the hydrolysis of ATP and ADP, and a decrease in adenosine deamination in lymphocytes of MetS patients before the exercise intervention were observed (Pexercise training after 30 weeks of intervention. Additionally, exercise training reduced the inflammatory and hepatic markers to baseline levels after 30 weeks of exercise. Our results clearly indicated alteration in ectonucleotidase enzymes in lymphocytes in the MetS, whereas regular exercise training had a protective effect on the enzymatic alterations and on inflammatory and hepatic parameters, especially if it is performed regularly and for a long period. © Georg Thieme Verlag KG Stuttgart · New York.

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression by Ganoderma Lucidum Polysaccharides

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Li-Xin Sun

2014-01-01

Full Text Available Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

Organ distribution of 111In-oxine labeled lymphocytes in normal subjects and in patients with chronic lymphocytic leukemia and malignant lymphoma

International Nuclear Information System (INIS)

Matsuda, Shin; Uchida, Tatsumi; Yui, Tokuo; Kariyone, Shigeo

1982-01-01

T and B lymphocyte survival and organ distribution were studied by using 111 In-oxine labeled autologous lymphocytes in 3 normal subjects, 3 patients with chronic lymphocytic leukemia (CLL) and 9 with malignant lymphoma (ML).FDisappearance curves of the labeled lymphocytes showed two exponential components in all cases. The half time of the first component was within 1 hour in all cases. That of the second one was 50.7 +- 6.4 hours for all lymphocytes, 52.0 +- 5.5 hours for T lymphocytes and 31.6 +- 4.9 hours for B lymphocytes in normal subjects, 192.6 hours for T-CLL and 57.7 +- 46.9 hours for B-CLL, and 60.2 +- 30.7 hours for T cell type of malignant lymphoma (T-ML) and 63.7 +- 24.5 hours for B cell type of malignant lymphoma (B-ML). These data might suggest that all lymphocyte disappearance curve reflected T lymphocyte disappearance curve chiefly, and the half time of B lymphocytes was shorter than that of T lymphocytes. In the T-CLL, the half time of the second component prolonged extremely in comparison with that of normal T lymphocytes. The labeled cells were accumulated in the lungs, spleen and liver immediately after the infusion, then in the spleen most remarkably 1 hour after the infusion in all cases. The radioactivity over the bone marrow was observed from 1 hour in all cases and that of lymph nodes were first noticed 18 hours after the infusion in T-CLL and T-ML, 68 hours in B-CLL but were not noticed in normal subjects and B-ML. The recovery of labeled cells in the blood was 28.5 +- 7.9% for all lymphocytes, 19.7 +- 1.9% for T lymphocytes and 11.0 +- 5.1% for B lymphocytes in normal subjects, 25.8 +- 1.6% for CLL, and 17.6 +- 11.0% for T-ML, 7.7 +- 5.2% for B-ML, respectively. (J.P.N.)

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

Science.gov (United States)

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Local lymphocytes and nitric oxide synthase in the uterine cervical stroma of patients with grade III cervical intraepithelial neoplasia

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Cléber Sergio da Silva

2010-01-01

Full Text Available OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas. The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3, 35.5 (± 9.5, and 50 (± 11.2 years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3, cytotoxic lymphocytes (CD8, B lymphocytes (CD20, macrophages (CD68 and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control, at the intraepithelial lesion (CIN cases, and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05 in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05. CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion.

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

International Nuclear Information System (INIS)

Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael; Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele; Geinitz, Hans; Duma, Marciana N.

2017-01-01

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3 + T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [de

Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Barsegian, Vahe; Moeckel, Daniel [Helios Kliniken, Institute of Nuclear Medicine, Schwerin (Germany); Mueller, Stefan P.; Bockisch, Andreas [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Horn, Peter A.; Lindemann, Monika [University Hospital Essen, Institute for Transfusion Medicine, Essen (Germany)

2017-02-15

Therapy with the alpha-emitter radium-223 chloride ({sup 223}Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if {sup 223}Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving {sup 223}Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after {sup 223}Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy.

Science.gov (United States)

Romano, Alessandra; Parrinello, Nunziatina Laura; Vetro, Calogero; Chiarenza, Annalisa; Cerchione, Claudio; Ippolito, Massimo; Palumbo, Giuseppe Alberto; Di Raimondo, Francesco

2018-06-01

Recent reports identify NLR (the ratio between absolute neutrophils counts, ANC, and absolute lymphocyte count, ALC), as predictor of progression-free survival (PFS) and overall survival (OS) in cancer patients. We retrospectively tested NLR and LMR (the ratio between absolute lymphocyte and monocyte counts) in newly diagnosed Hodgkin lymphoma (HL) patients treated upfront with a PET-2 risk-adapted strategy. NLR and LMR were calculated using records obtained from the complete blood count (CBC) from 180 newly diagnosed HL patients. PFS was evaluated accordingly to Kaplan-Meier method. Higher NLR was associated to advanced stage, increased absolute counts of neutrophils and reduced count of lymphocytes, and markers of systemic inflammation. After a median follow-up of 68 months, PFS at 60 months was 86.6% versus 70.1%, respectively, in patients with NLR ≥ 6 or NLR PET-2 scan (p PET-2 was an independent predictor of PFS in multivariate analysis. Advanced-stage patients (N = 119) were treated according to a PET-2 risk-adapted protocol, with an early switch to BEACOPP regimen in case of PET-2 positivity. Despite this strategy, patients with positive PET-2 still had an inferior outcome, with PFS at 60 months of 84.7% versus 40.1% (negative and positive PET-2 patients, respectively, p PET-2 status and to a lesser extend NLR in advanced stage, while LMR maintained its significance in early stage. By focusing on PET-2 negative patients, we found that patients with NLR ≥ 6.0 or LMR PET-2 scan, NLR and LMR can result in a meaningful prognostic system that needs to be further validated in prospective series including patients treated upfront with PET-2 adapted-risk therapy.

Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.

Science.gov (United States)

Grzegorzewska, Alicja E; Leander, Magdalena

2005-01-01

Dietary deficiency causes abnormalities in circulating lymphocyte counts. For the present paper, we evaluated correlations between total and subpopulation lymphocyte counts (TLC, SLCs) and parameters of nutrition in peritoneal dialysis (PD) patients. Studies were carried out in 55 patients treated with PD for 22.2 +/- 11.4 months. Parameters of nutritional status included total body mass, lean body mass (LBM), body mass index (BMI), and laboratory indices [total protein, albumin, iron, ferritin, and total iron binding capacity (TIBC)]. The SLCs were evaluated using flow cytometry. Positive correlations were seen between TLC and dietary intake of niacin; TLC and CD8 and CD16+56 counts and energy delivered from protein; CD4 count and beta-carotene and monounsaturated fatty acids 17:1 intake; and CD19 count and potassium, copper, vitamin A, and beta-carotene intake. Anorexia negatively influenced CD19 count. Serum albumin showed correlations with CD4 and CD19 counts, and LBM with CD19 count. A higher CD19 count was connected with a higher red blood cell count, hemoglobin, and hematocrit. Correlations were observed between TIBC and TLC and CD3 and CD8 counts, and between serum Fe and TLC and CD3 and CD4 counts. Patients with a higher CD19 count showed a better clinical-laboratory score, especially less weakness. Patients with a higher CD4 count had less expressed insomnia. Quantities of ingested vitamins and minerals influence lymphocyte counts in the peripheral blood of PD patients. Evaluation of TLC and SLCs is helpful in monitoring the effectiveness of nutrition in these patients.

Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo.

Science.gov (United States)

Costa, Mónica; Cruz, Eugénia; Oliveira, Susana; Benes, Vladimir; Ivacevic, Tomi; Silva, Maria João; Vieira, Inês; Dias, Francisco; Fonseca, Sónia; Gonçalves, Marta; Lima, Margarida; Leitão, Catarina; Muckenthaler, Martina U; Pinto, Jorge; Porto, Graça

2015-01-01

Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH.

Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients

DEFF Research Database (Denmark)

Iversen, Trine Zeeberg; Brimnes, Marie Klinge; Nikolajsen, Kirsten

2013-01-01

Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4......(+) T cells would be associated to the clinical benefits of TMZ. Patients were treated with TMZ (150 mg/m(2) daily, every two weeks on a four-week schedule) until disease progression. Changes in T-lymphocyte subsets were characterized by flow cytometry. All patients enrolled in this study had...

Immunophenotypic lymphocyte profiles in human african trypanosomiasis.

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Caroline Boda

Full Text Available Human African trypanosomiasis (HAT is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+. Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+, but memory CD8 T-cell levels (CD8+CD45RA2 were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L2. No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2. However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging.

Activation of cytotoxic lymphocytes in patients with scrub typhus

NARCIS (Netherlands)

de Fost, Maaike; Chierakul, Wirongrong; Pimda, Kriangsak; Dondorp, Arjen M.; White, Nicholas J.; van der Poll, Tom

2005-01-01

Thai patients with scrub typhus caused by the intracellular pathogen Orientia tsutsugamushi displayed elevated plasma concentrations of granzymes A and B, interferon-gamma (IFN)-gamma-inducible protein 10, and monokine induced by IFN-gamma. These data suggest that activation of cytotoxic lymphocytes

Detection of silver-stained nucleolar organizer regions in the peripheral blood T lymphocytes in nasopharyngeal carcinoma patients

International Nuclear Information System (INIS)

Li Xianming; Wu Dong; Chen Shanyi; Ren Zheping; Chen Yixin; Wang Xiuqing

2002-01-01

Objective: To evaluate the clinical significance of detecting silver-stained nucleolar organizer regions (Ag-NOR) in the peripheral blood T lymphocytes in nasopharyngeal carcinoma (NPC) patients. Methods: Ag-NOR in the peripheral blood T lymphocytes detected in 36 healthy subjects served as control. Those in 73 newly diagnosed but untreated, 11 recurrent (and/or metastatic) and 32 treated NPC patients in follow-up were monitored. The dynamic variations in the level of Ag-NORs in the peripheral blood T lymphocytes in the pre-radiotherapy (pre-RT), during RT and post-RT were evaluated in part of the newly diagnosed patients. Results: The level of Ag-NORs in the peripheral blood T lymphocytes in all groups of NPC patients were significantly lower as compared to the health controls (P 0.05). The level of Ag-NORs during RT significantly decreased as compared to that of pre-RT (P 0.05). Conclusions: Detection of Ag-NORs in the peripheral blood T lymphocytes is of significance in evaluating the outcome, predicting prognosis and even in making the diagnosis and staging for NPC patients

Chronic lymphocytic thyroiditis (CLT) has a positive prognostic value in papillary thyroid cancer (PTC) patients: the potential key role of Foxp3+ T lymphocytes.

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Pilli, T; Toti, P; Occhini, R; Castagna, M G; Cantara, S; Caselli, M; Cardinale, S; Barbagli, L; Pacini, F

2017-12-11

An impact of chronic lymphocytic thyroiditis (CLT) on papillary thyroid cancer (PTC) outcome has long been advocated but it is still controversial. The aim of this study was to evaluate the prognostic value of CLT in a retrospective cohort of PTC patients and to characterize the lymphocytic subpopulations and infiltrate (LI). We assessed 375 PTC patients, aged 45.2 ± 16.4 years, and treated with thyroidectomy and radioiodine remnant ablation, with a mean follow-up of 6.28 ± 3.86 years. In a subgroup of patients (n = 81) tissue sections were reviewed for the presence of CLT or lymphocytes associated with tumor in absence of background thyroiditis (TAL); cytotoxic CD8+/regulatory Foxp3+ T lymphocyte (CD8+/Foxp3+) ratio was characterized by immunohistochemistry: a low ratio is suggestive of a less effective anti tumor immune response. Seventy-five/375 patients (20%) had a histological diagnosis of CLT and showed at the last follow-up a significantly better outcome compared to those with no CLT (cure rate: 91.8 versus 76.3%, p = 0.003). LI was characterized in 81 PTC patients (24 with CLT and 57 with TAL): the peri-tumoral CD8+/Foxp3+ ratio was lower in patients not cured at the final evaluation. Our data suggest that concurrent CLT has a protective effect on PTC outcome and that the imbalance between cytotoxic and regulatory T lymphocytes in the peri-tumoral TAL may affect the tumor-specific immune response favoring a more aggressive behavior of cancer.

Lymphocyte function following radium-223 therapy in patients with metastasized, castration-resistant prostate cancer

International Nuclear Information System (INIS)

Barsegian, Vahe; Moeckel, Daniel; Mueller, Stefan P.; Bockisch, Andreas; Horn, Peter A.; Lindemann, Monika

2017-01-01

Therapy with the alpha-emitter radium-223 chloride ("2"2"3Ra) is an innovative therapeutic option in patients with metastasized, castration-resistant prostate cancer. However, radiotherapy can lead to hematopoietic toxicity. The aim of this study was to determine if "2"2"3Ra therapy induces an impairment of cellular antimicrobial immune responses. In 11 patients receiving "2"2"3Ra treatment, lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) were determined, using lymphocyte transformation testing and ELISpot, respectively. Lymphocyte function after stimulation with mitogens and microbial antigens was assessed prior to therapy and at day 1, 7 and 28 after therapy. Lymphocyte proliferation and the production of interferon-γ and interleukin-10 towards mitogens and antigens remained unchanged after therapy. Consistent with these in vitro data, we did not observe infectious complications after treatment. The results argue against an impairment of lymphocyte function after "2"2"3Ra therapy. Thus, immune responses against pathogens should remain unaffected. (orig.)

Radiosensitiviness of blood lymphocytes from skin cancer patients and healthy volunteers as determined by micronucleus assay

International Nuclear Information System (INIS)

Lohmann, Tania Helena Ochi.

1995-01-01

Cancer, a major death cause in developed countries, has been related to somatic mutations that could be detected by cytogenetic analysis. Among the tools used in these tests, the micronucleus assay has been largely applied at population surveillance, biological dosimetry and early detection of groups with higher risks to developing cancers. In this study, we analysed the chromosome susceptibility of blood lymphocytes from basocellular skin cancer patients and healthy volunteers. The cytogenetic analysis was performed by a micronucleus assay, using progressive doses of ionizing radiation from a 60 Co source as mutagen. Briefly, the blood lymphocytes were irradiated in vitro, as processed by the cytokinesis-blocked method. The micronucleus frequency and distribution, cell cycle kinetics, nucleation index and dose-response relationship were determined in each patient. The results showed that the basocellular skin cancer patients lymphocytes presented higher spontaneous micronucleus frequency as compared with those from healthy young volunteers but lower than healthy now young volunteers . The radiation-induced micronucleus analysis showed that the basocellular skin cancer patients' lymphocytes presented similar proportion of damage lymphocytes as compared with those from healthy volunteers. Nevertheless, the magnitude of this damage was higher in this group with doses. Higher than 400 c Gy, which was not occurred in healthy volunteers. Cell cycle kinetics, as determined by the nucleation index, was lower in basocellular skin cancer patients as compared with healthy volunteers, indicating a more slow cell cycle. Our data showed that the lymphocytes from carcinoma basocellular patients were more radiosensitive as compared with those form healthy volunteers. (author). 159 refs., 21 figs., 16 tabs

Mutagenicity of hydroxyurea in lymphocytes from patients with sickle cell disease

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Khayat André Salim

2004-01-01

Full Text Available Hydroxyurea is commonly used in the treatment of myeloproliferative diseases and in patients with sickle cell disease (SCD. The use of this antineoplastic agent in patients with SCD is justified because of the drug's ability to increase fetal hemoglobin levels, thereby decreasing the severity of SCD. However, high doses or prolonged treatment with hydroxyurea can be cytotoxic or genotoxic for these patients, with an increased risk of developing acute leukemia. This danger can be avoided by monitoring the lymphocytes of patients treated with hydroxyurea. Cytogenetic tests are important endpoints for monitoring the physiological effects of physical and chemical agents, including drugs. In this work, we assessed the genotoxicity of hydroxyurea in short-term cultures of lymphocytes from SCD patients. Hydroxyurea was not cytotoxic or genotoxic at the concentrations tested in the G2 phase of the cell cycle. These results support the use of hydroxyurea in the treatment of SCD, although further work is necessary to understand the effects of this drug in vivo.

[Causes of lymphocytic meningitis in people with HIV admitted to the Infectious Disease department of Conakry].

Science.gov (United States)

Traoré, F A; Cissoko, Y; Tounkara, T M; Sako, F B; Mouelle, A D; Kpami, D O; Traoré, M; Doumbouya, M

2015-01-01

The advent of HIV infection has significantly changed the distribution of the causes of lymphocytic meningitis. The objective of this study was to identify these causes among persons with HIV hospitalized in the infectious disease department of the CHU of Conakry. This retrospective study examined hospital records of patients with HIV infection admitted for lymphocytic meningitis over a 10-year period. Of the 8649 hospitalizations in the department during the study period, 3167 patients had HIV infection, and 85 of the latter were diagnosed with lymphocytic meningitis. Slightly more than half were male (sex ratio M/F = 1.1). Their mean age was 32 years. Of these 85 patients, 73 were positive for HIV-1 only and 12 for HIV1+2. A CD4 count was performed only in 13/85 patients and averaged 140 cells/mm3. The main causes associated with lymphocytic meningitis were cryptococcosis (58%), toxoplasmosis (5%), and tuberculosis (2%). Streptococcus pneumoniae, Neisseria meningitidis, and Hæmophilus influenzae were also identified in 16% of cases. In 18% of cases no microbe was identified. The overall lethality rate was 68%; it reached 100% for tuberculous meningitis and for the cases without any identified cause and was 75%-76% for the patients with toxoplasmosis and cryptococcosis. The survival rate was 100% for all bacterial causes. A cause for lymphocytic meningitis was identified in more than 81% of the patients in our series, and the most common microbe was Cryptococcus neoformans. A better microbiological technical platform and improved accessibility to treatment would enable us to provide more relevant results and treatment.

Apoptotic response of irradiated T-Lymphocytes. An epidemiologic study in canine radiotherapy patients

International Nuclear Information System (INIS)

Stankeova, S.; Kaser-Hotz, B.; Crompton, N.E.A.; Blattmann, H.; Theiler, P.; Emery, G.C.; Roos, M.

2003-01-01

Background: Evaluation of radiation-induced apoptosis in T-lymphocytes was developed for human medicine in order to predict the sensitivity of individual patients to radiation therapy and has regular use in cases of suspected hypersensitivity. A major goal of the present study was to evaluate the usefulness of the apoptosis assay in veterinary medicine for application in radiation sensitivity testing. The main goal was to examine potential changes in sensitivity of T-lymphocytes to radiation-induced apoptosis during the course of radiation treatment. This is a clear example of the advantageous use of spontaneous canine tumors to augment human cancer research. Material and Methods: Blood was collected in heparin tubes, diluted 1:10 in RPMI medium, irradiated with X-rays and incubated for 48 h. T-lymphocytes were labeled using FITC-conjugated antibodies, erythrocytes were lysed, and DNA stained with propidium iodide. For cell analysis, a Becton Dickinson FACScan flow cytometer was used. Radiation-induced apoptosis in T-lymphocytes was quantified. Blood samples from tumor-bearing dogs were taken before the first fraction and at the end of radiation therapy. Results: Apoptosis in lymphocytes is dependent on donor age and donor weight. Tumor-bearing dogs when compared with healthy dogs showed no significant differences in levels of induced apoptosis. No significant changes were seen in the levels of radiation-induced apoptosis in blood taken before, during, or after radiation therapy. Conclusion: The leukocyte apoptosis assay can be successfully applied to canine patients, and a wide spectrum of sensitivities to radiation-induced apoptosis is observed. The sensitivity of a patient's peripheral blood T-lymphocytes to radiation-induced apoptosis does not change as a result of the trauma of radiotherapy during the course of tumor treatment. (orig.)

Evaluation of four methods for separation of lymphocytes from normal individuals and patients with cancer and tuberculosis.

Science.gov (United States)

Patrick, C C; Graber, C D; Loadholt, C B

1976-01-01

An optimal technique was sought for lymphocyte recovery from normal and chronic diseased individuals. Lymphocytes were separated by four techniques: Plasmagel, Ficoll--Hypaque, a commercial semiautomatic method, and simple centrifugation using blood drawn from ten normal individuals, ten cancer patients, and ten tuberculosis patients. The lymphocyte mixture obtained after using each method was analyzed for percent recovery, amount if contamination by erythrocytes and neutrophils, and percent viability. The results show that the semiautomatic method yielded the best percent recovery of lymphocytes for normal individuals, while the simple centrifugation method contributed the highest percent recovery for cancer and tuberculosis patients. The Ficoll-Hypaque method gave the lowest erythrocyte contamination for all three types of individuals tested, while the Plasmagel method gave the lowest neutrophil contamination for all three types of individuals. The simple centrifugation method yielded all viable lymphocytes and thus gave the highest percent viability.

Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis

Science.gov (United States)

Calder, Elizabeth A.; McLeman, Dena; Irvine, W. J.

1973-01-01

Lymphocytes from healthy donors were incubated with serum samples from nine patients with Hashimoto thyroiditis and subsequently shown to be cytotoxic to chicken red blood cells (Ch. RBC) coated with thyroglobulin. Target cell death was estimated using a standard 51Cr release assay system. Lymphocytes pre-incubated with Hashimoto serum caused a mean% 51Cr release of 13·11±2·83 (SEM) from thyroglobulin-coated Ch. RBC and a mean% 51Cr release of 1·22±0·65 from uncoated Ch. RBC. Untreated lymphocytes caused no significant isotope release from either uncoated or thyroglobulin coated target cells. PMID:4800956

Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma

International Nuclear Information System (INIS)

Toyohira, Ken; Yasumoto, Kosei; Manabe, Hideo; Ohta, Mitsuo; Terashima, Hiromi

1979-01-01

Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I and II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size. (author)

Fish Lymphocytes: An Evolutionary Equivalent of Mammalian Innate-Like Lymphocytes?

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Giuseppe Scapigliati

2018-05-01

Full Text Available Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity. However, the homology between fish lymphocytes and mammalian innate-like lymphocytes is an issue poorly considered in comparative immunology. Increasing experimental evidence suggests that fish lymphocytes could have developmental, morphological, and functional features in common with innate-like lymphocytes of mammals. Despite such similarities, information on possible links between conventional fish lymphocytes and mammalian innate-like lymphocytes is missing. The aim of this review is to summarize and describe available findings about the similarities between fish lymphocytes and mammalian innate-like lymphocytes, supporting the hypothesis that mammalian γδT cells and B1-B cells could be evolutionarily related to fish lymphocytes.

Lymphocyte-platelet crosstalk in Graves' disease.

Science.gov (United States)

Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

Clinical Significance of Preoperative Neutrophil Lymphocyte Ratio versus Platelet Lymphocyte Ratio in Patients with Small Cell Carcinoma of the Esophagus

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Ji-Feng Feng

2013-01-01

Full Text Available Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various of cancers. The aim of this study was to determine the prognostic values of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR in patients with small cell carcinoma of the esophagus (SCCE. Preoperative NLR and PLR were evaluated in 43 patients with SCCE from January 2001 to December 2010. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. Receiver operating characteristic (ROC curves were also plotted to verify the accuracy of NLR and PLR for survival prediction. Patients with PLR ≥150 had significantly poorer (relapse-free survival RFS and (overall survival OS compared to patients with PLR <150. However, RFS or OS did not differ according to NLR categories (<3.5 and ≥3.5. The areas under the curve (AUC indicated that PLR was superior to NLR as a predictive factor. The results of the present study conclude that PLR is superior to NLR as a predictive factor in patients with SCCE.

Estimation of CD4+ and CD8+ T-lymphocytes in human immunodeficiency virus infection and acquired immunodeficiency syndrome patients in Manipur

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Singh H

2007-01-01

Full Text Available Purpose : To estimate and stratify CD4 + and CD8 + T-lymphocyte levels in human immunodeficiency virus (HIV infected (asymptomatic and acquired immunodeficiency syndrome (AIDS patients (symptomatic and correlate the clinical features of the patients with CD4+ and CD8+ lymphocyte level. Methods : Between April 2002 and September 2003, a total of 415 HIV seropositive adult patients (297 males and 118 females attending Regional Institute of Medical Sciences (RIMS hospitals were tested for CD4+ and CD8+ T-lymphocytes by fluorescent activated cell sorter (FACS counter (Becton Dickinson. Symptomatic patients were diagnosed as per NACO clinical case definition. Results : Ranges of 0-50, 51-100, 101-200, 201-300, 301-400, 401-500 and above 500 CD4+ T-lymphocyte per microlitre were seen in 68, 52, 101, 73, 47, 31 and 43 patients respectively whereas CD8+ T-lymphocyte ranges of 0-300, 301-600, 601-900, 901-1500, 1501-2000, 2001-3500 per microlitre were seen in 29, 84, 92, 145, 40 and 25 patients respectively. One hundred and fifty patients were asymptomatic and 265 were symptomatic. CD4/CD8 ratio in asymptomatics and symptomatics were 0.13-1.69 and 0.01-0.93 respectively. Tuberculosis and candidiasis occurred in CD4+ T-lymphocyte categories between 0-400 cells per mL in symptomatics. However, cryptosporidiosis, toxoplasmosis, herpes zoster, cryptococcal meningitis, Pneumocystis carinii pneumonia, penicilliosis and cytomegalovirus retinitis were seen in patients having CD4+ T-lymphocyte less than 200 per mL. Conclusions : CD4+ T-lymphocyte was decreased in both asymptomatic and symptomatic HIV patients, The decrease was greater in symptomatics while CD8+ T-lymphocyte was increased in both except advanced stage symptomatics. CD4:CD8 ratio was reversed in both groups. Opportunistic infections correlated with different CD4+ T-lymphocyte categories.

Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis.

Science.gov (United States)

Wang, Yuchen; Fuentes, Harry E; Attar, Bashar M; Jaiswal, Palash; Demetria, Melchor

Recent studies attribute promising prognostic values to various inflammatory biomarkers in acute pancreatitis, including the following: the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW). We aimed to determine the performance of these biomarkers for detecting disease severity in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). We retrospectively reviewed 110 patients with HTG-AP and compared the NLR, PLR, and RDW in different severity groups. We performed receiver-operating characteristic (ROC) analysis to identify the optimal cut-off value for NLR to predict severe AP. NLR was significantly higher in patients with severe AP than mild and moderately severe AP (14.6 vs. 6.9, p analysis (Odds ratio 6.71, p = 0.019). NLR represents an inexpensive, readily available test with a promising value to predict disease severity in HTG-AP. Among the three inflammatory biomarkers, NLR has the highest discriminatory capacity for severe HTG-AP, with an optimal cut-off value of 10. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients

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Lardon Filip

2010-04-01

Full Text Available Abstract Background There is growing evidence that both local and systemic inflammatory responses play an important role in the progression of a variety of solid tumors. Colorectal cancer results from the cumulative effect of sequential genetic alterations, leading to the expression of tumor associated antigens possibly inducing a cellular anti-tumor immune response. It is well recognized that cytotoxic lymphocytes constitute one of the most important effector mechanisms of anti-tumor-immunity. However, their potential prognostic influence in colorectal cancer remains controversial. Aim of the study was to examine infiltration of CD3+ and CD8+ lymphocytes in colorectal cancer and their prognostic potential. Two-hundred-fifteen colorectal cancer cases, previously analyzed for microsatellite instability (MSI, were selected for immunohistochemical detection of CD3+, CD8+ infiltration and the expression of granzyme B. Prognostic relevance was assessed by survival analysis. Results Strong correlations were found between the infiltration of lymphocytes and several clinicopathological variables. Survival analysis revealed that intra-epithelial infiltration of CD3+ and CD8+ T lymphocytes and stromal infiltration of CD3+ lymphocytes had a major impact on the patients' overall survival in the univariate analysis, however independent of their association with MSI-status. In addition, it was also demonstrated that there was an important disease specific survival advantage for patients with microsatellite stable (MSS tumors containing intraepithelial CD8+ tumor infiltrating lymphocytes. When samples were analyzed for colon cancer and rectal cancer separately, the results of the overall population were confirmed in colon cancer only. When entered into a multiple Cox regression analysis adjusting for other possible important confounding factors, the strong impact of lymphocyte infiltration on overall survival was not maintained. Only early stage and young age

Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients.

Science.gov (United States)

Manson, Joanna; Cole, Elaine; De'Ath, Henry D; Vulliamy, Paul; Meier, Ute; Pennington, Dan; Brohi, Karim

2016-06-07

Early survival following severe injury has been improved with refined resuscitation strategies. Multiple organ dysfunction syndrome (MODS) is common among this fragile group of patients leading to prolonged hospital stay and late mortality. MODS after trauma is widely attributed to dysregulated inflammation but the precise mechanics of this response and its influence on organ injury are incompletely understood. This study was conducted to investigate the relationship between early lymphocyte responses and the development of MODS during admission. During a 24-month period, trauma patients were recruited from an urban major trauma centre to an ongoing, observational cohort study. Admission blood samples were obtained within 2 h of injury and before in-hospital intervention, including blood transfusion. The study population was predominantly male with a blunt mechanism of injury. Lymphocyte subset populations including T helper, cytotoxic T cells, NK cells and γδ T cells were identified using flow cytometry. Early cytokine release and lymphocyte count during the first 7 days of admission were also examined. This study demonstrated that trauma patients who developed MODS had an increased population of NK dim cells (MODS vs no MODS: 22 % vs 13 %, p < 0.01) and reduced γδ-low T cells (MODS vs no MODS: 0.02 (0.01-0.03) vs 0.09 (0.06-0.12) × 10^9/L, p < 0.01) at admission. Critically injured patients who developed MODS (n = 27) had higher interferon gamma (IFN-γ) concentrations at admission, compared with patients of matched injury severity and shock (n = 60) who did not develop MODS (MODS vs no MODS: 4.1 (1.8-9.0) vs 1.0 (0.6-1.8) pg/ml, p = 0.01). Lymphopenia was observed within 24 h of injury and was persistent in those who developed MODS. Patients with a lymphocyte count of 0.5 × 10(9)/L or less at 48 h, had a 45 % mortality rate. This study provides evidence of lymphocyte activation within 2 h of injury, as demonstrated by

Discrimination of human cytotoxic lymphocytes from regulatory and B-lymphocytes by orthogonal light scattering

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; de Grooth, B.G.; ten Napel, C.H.H.; van Berkel, W.; Greve, Jan

1986-01-01

Light scattering properties of human lymphocyte subpopulations selected by immunofluorescence were studied with a flow cytometer. Regulatory and B-lymphocytes showed a low orthogonal light scatter signal, whereas cytotoxic lymphocytes identified with leu-7, leu-11 and leu-15 revealed a large

CD4 T lymphocyte counts in patients undergoing splenectomy during living donor liver transplantation.

Science.gov (United States)

Natsuda, Koji; Eguchi, Susumu; Takatsuki, Mistuhisa; Soyama, Akihiko; Hidaka, Masaaki; Hara, Takanobu; Kugiyama, Tota; Baimakhanov, Zhassulan; Ono, Shinichiro; Kitasato, Amane; Fujita, Fumihiko; Kanetaka, Kengo; Kuroki, Tamotsu

2016-02-01

The role of splenectomy in increasing the CD4-positive T lymphocyte counts (hereafter: CD4 counts) and the CD4 to CD8 ratio have not yet been fully investigated, especially in the case of HIV-positive patients undergoing liver transplantation (LT). The change in the total lymphocyte counts of 32 patients who underwent one-stage splenectomy with living donor (LD) LT with (n=13) or without rituximab (RTX, n=19) therapy were examined to validate our cohort of ABO-incompatible LDLT with RTX. Subsequently, perioperative changes in CD4 counts and the CD 4 to CD8 ratio were measured in 13 patients who underwent ABO-incompatible LDLT/RTX with splenectomy. (1) The administration of RTX did not significantly affect the total lymphocyte counts of patients after LDLT/splenectomy in any of the observation periods. (2) The CD4 counts were significantly higher at 2years after LDLT in comparison to the perioperative CD4 counts but not within the 3-month period (p=0.039). The CD4/CD8 ratio gradually decreased after LDLT/splenectomy under RTX treatment. An immediate increase in the CD4 counts therefore cannot be expected after LDLT with splenectomy. The total lymphocyte and CD4 counts were rather stable in the peritransplant period even in ABO incompatible LDLT with RTX. Copyright © 2015 Elsevier B.V. All rights reserved.

[Common variable immunodeficiency: Clinical and immunological characterization of patients and homogeneous subgroup definition by means of B lymphocyte subpopulation typing].

Science.gov (United States)

Vélez, Alejandra Catalina; Castaño, Diana María; Gómez, Rubén Darío; Orrego, Julio César; Moncada, Marcela; Franco, José Luis

2015-01-01

Common variable immunodeficiency is a heterogeneous syndrome characterized by recurrent infections, hypogammaglobulinemia and defective production of specific antibodies. Abnormalities in peripheral blood lymphocyte subpopulations, in particular of B lymphocytes, allow the classification of patients into homogeneous groups. To perform a clinical and immunological characterization and to evaluate lymphocyte subpopulations of twelve Colombian patients with common variable immunodeficiency in order to define homogeneous groups. We reviewed medical records and evaluated serum immunoglobulins (Ig), lymphoproliferation, delayed hypersensitivity and used flow cytometry to quantify peripheral blood total lymphocyte and B cell populations. All patients had recurrent respiratory and/or gastrointestinal infections, while some also had infections affecting other systems. All patients had abnormally low serum IgG levels, while IgA and IgM levels were reduced in nine and ten patients, respectively. Lymphoproliferation to mitogen was lower in patients than in healthy controls but lymphoproliferation to specific antigen was normal in all. Flow cytometry revealed high numbers of T cells in three patients, while seven had a low CD4+/CD8+ ratio and four had reduced NK cells . Eleven patients had normal B cell counts, and eight of them also showed decreased memory B lymphocytes, and four had increased transitional or CD21 low B lymphocytes. Lymphocyte typing allowed assigning all but one patient to homogeneous groups according to international classification schemes, indicating the necessity of including more criteria until an ideal classification is achieved. This study will lead to a better medical monitoring of common variable immunodeficiency patients in groups at high risk of developing clinical complications.

Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia.

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Cubillos-Zapata, Carolina; Avendaño-Ortiz, Jose; Córdoba, Raúl; Hernández-Jiménez, Enrique; Toledano, Victor; Pérez de Diego, Rebeca; López-Collazo, Eduardo

2016-01-01

Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimulus in CD14 + cells, improving levels of phospho-Erk1/2 and antigen presentation. Meanwhile, ibrutinib drove Th1-selective pressure in T lymphocytes, thus, reducing the PD-1 and PDL-1 expression. Our data suggest the impact of BTK inhibition along with immunomodulation on the innate immune response and a switch to the specific adaptive immune response, which might help to decrease infectious complications. The potential effect of ibrutinib on CLL patient outcomes is worthy of further study, because infections could be reduced with the use of ibrutinib.

Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Science.gov (United States)

2018-01-26

Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

Apoptosis in peripheral blood lymphocytes of healthy donors and patients with laryngeal cancer after γ-irradiation in vitro

International Nuclear Information System (INIS)

Orlova, N.V.; Smirnova, S.G.; Zamulaeva, I.A.; Andreev, V.G.; Ryabchenko, N.I.; Saenko, A.S.

2001-01-01

Apoptosis in peripheral blood lymphocytes of healthy donors and cancer patients after γ-radiation with different doses is studied by the flow cytometry method. Wide intra- and interindividual variabilities of the lymphocyte radiosensitivity by different donors are observed. The radiosensitivity does not depend on the subpopulation composition of the lymphocyte pool. The persons with very low and high lymphocyte radiosensitivities are found significantly more often among the cancer patients than among the healthy donors. One can suggest that this method is useful to define risk groups with regard to radiogenic neoplasms and prognosis of radiotherapy efficiency [ru

Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer.

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Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

2015-09-14

To evaluate the prognostic significance of the lymphocyte to monocyte ratio (LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy. A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pre-treatment LMR values were measured within one week before the initiation of chemotherapy, while post-treatment LMR values were measured eight weeks after the initiation of chemotherapy. The median pre-treatment LMR was 4.16 (range: 0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38, 66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pre-treatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate (P = 0.0011). Moreover, patients who demonstrated low pre-treatment LMR and normalization after treatment exhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values. The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.

ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

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Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

2017-03-09

Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

Radiobiological heterogeneity of leukemic lymphocyte precursors from acute lymphoblastic leukemia patients

International Nuclear Information System (INIS)

Uckun, F.M.; Kim, T.H.; Ramsay, N.C.; Min, W.S.; Song, C.W.

1989-01-01

The report outlines the authors' findings on the radiobiological features of leukemic lymphocyte precursors from acute lymphoblastic leukemia (ALL) patients. A marked heterogeneity existed between different cell lines, with a remarkable radioresistance and repair capacity in some ALL patients and an acute radiosensitivity in the absence of a detectable repair capacity in others. (U.K.)

AID protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma is associated with poor prognosis and complex genetic alterations.

Science.gov (United States)

Leuenberger, Mona; Frigerio, Simona; Wild, Peter J; Noetzli, Franziska; Korol, Dimitri; Zimmermann, Dieter R; Gengler, Carole; Probst-Hensch, Nicole M; Moch, Holger; Tinguely, Marianne

2010-02-01

The biological behavior of chronic lymphocytic leukemia and small lymphocytic lymphoma is unpredictable. Nonetheless, non-mutated IgV(H) gene rearrangement, ATM (11q22-23) and p53 (17p13) deletion are recognized as unfavorable prognosticators in chronic lymphocytic leukemia. The mRNA expression of activation-induced cytidine deaminase (AID), an enzyme indispensable for somatic hypermutation processes, was claimed to be predictive of non-mutated chronic lymphocytic leukemia cells in blood. Here, we evaluated AID protein expression compared with known molecular and immunohistochemical prognostic indicators in 71 chronic lymphocytic leukemia/small lymphocytic lymphoma patients using a tissue microarray approach. We found AID heterogeneously expressed in tumor cells as shown by colocalization analysis for CD5 and CD23. Ki-67 positive paraimmunoblasts of the proliferation centers displayed the highest expression. This observation is reflected by a significant association of AID positivity with a high proliferation rate (P=0.012). ATM deletion was detected in 10% (6/63) of patients and p53 deletion in 19% (13/67) of patients. Moreover, both ATM (P=0.002) and p53 deletion (P=0.004) were significantly associated with AID. IgV(H) gene mutation was seen in 45% (27/60) of patients. Twenty-five percent (17/69) of patients with AID-positive chronic lymphocytic leukemia/small lymphocytic lymphoma displayed a shorter survival than AID-negative chronic lymphocytic leukemia/small lymphocytic lymphoma patients (61 vs 130 months, P=0.001). Although there was a trend, we could not show an association with the IgV(H) gene mutation status. Taken together, our study shows that AID expression is an indicator of an unfavorable prognosis in chronic lymphocytic leukemia/small lymphocytic lymphoma patients, although it is not a surrogate marker for the IgV(H) status. Furthermore, the microenvironment of proliferation centers seems to influence AID regulation and might be an initiating factor

Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

DEFF Research Database (Denmark)

Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

2011-01-01

Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

[Significance of the alteration of Th17 cells in patients with chronic lymphocytic thyroiditis].

Science.gov (United States)

Song, Jin-Zhan; Wu, Han-Ni; Qian, Wei

2009-10-01

To investigate the alteration and its significance of T help 17 cells (Th17) in patients with chronic lymphocytic thyroiditis (CLT). Patients were divided into 3 groups: CLT patients with euthyroidism (n=15), CLT patients with hypothyroidism (n=30) and healthy control group (n=20). The ratio of Th17 lymphocytes subpopulations in the peripheral blood were evaluated by technique of flow cytometry. Production of thyroid autoantibody (TPO-Ab, TG-Ab) were measured by electro-chemiluminescence immunoassay (ECLIA). Compared with the healthy control group, in CLT group: The frequencies of Th17 in peripheral blood were found to be significantly higher in patients with CLT than healthy control group (PCLT patients than healthy control group (PCLT which may suggest a potential role for Th17 in the progression and happen of CLT.

FEATURES OF METABOLIC INDEXES OF BLOOD LYMPHOCYTES IN THE PATIENTS WITH EPIDURAL FIBROSIS FOLLOWING LUMBAR MICRODISCECTOMY

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N. V. Isaeva

2008-01-01

Full Text Available Abstract. A complex immunologic examination of fifty patients with clinically significant postoperative fibrosis has been performed. Immunogram indexes were determined, and activities of basic oxidation-reduction enzymes were investigated in blood lymphocytes. What concerned immune status of the patients under study, some peculiar features have been revealed, with respect to cellular and humoral compartments, i.e., relative increase in CD3+ population, a shift to CD4+ cells in the ratio of lymphocyte subpopulations, higher indexes of immune regulation and phagocytosis, increased IgG level, and lower content of IgA, as compared to appropriate controls. Metabolic parameters of lymphocytes reflect their functional activation, being expressed as an enhanced ability for intracellular synthetic processes, elevated functional activity of lymphocytes, and increased immune response. The general pattern of changes in immune status and metabolic indexes of lymphocytes allow us to assume participation of autoimmune component in progression of epidural fibrosis. The data obtained may be used in combined diagnostics and correction of this disorder. (Med. Immunol., vol. 10, N 6, pp 589-592.

Intestinal intraepithelial lymphocyte cytometric pattern is more accurate than subepithelial deposits of anti-tissue transglutaminase IgA for the diagnosis of celiac disease in lymphocytic enteritis.

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Fernando Fernández-Bañares

Full Text Available BACKGROUND & AIMS: An increase in CD3+TCRγδ+ and a decrease in CD3- intraepithelial lymphocytes (IEL is a characteristic flow cytometric pattern of celiac disease (CD with atrophy. The aim was to evaluate the usefulness of both CD IEL cytometric pattern and anti-TG2 IgA subepithelial deposit analysis (CD IF pattern for diagnosing lymphocytic enteritis due to CD. METHODS: Two-hundred and five patients (144 females who underwent duodenal biopsy for clinical suspicion of CD and positive celiac genetics were prospectively included. Fifty had villous atrophy, 70 lymphocytic enteritis, and 85 normal histology. Eight patients with non-celiac atrophy and 15 with lymphocytic enteritis secondary to Helicobacter pylori acted as control group. Duodenal biopsies were obtained to assess both CD IEL flow cytometric (complete or incomplete and IF patterns. RESULTS: Sensitivity of IF, and complete and incomplete cytometric patterns for CD diagnosis in patients with positive serology (Marsh 1+3 was 92%, 85 and 97% respectively, but only the complete cytometric pattern had 100% specificity. Twelve seropositive and 8 seronegative Marsh 1 patients had a CD diagnosis at inclusion or after gluten free-diet, respectively. CD cytometric pattern showed a better diagnostic performance than both IF pattern and serology for CD diagnosis in lymphocytic enteritis at baseline (95% vs 60% vs 60%, p = 0.039. CONCLUSIONS: Analysis of the IEL flow cytometric pattern is a fast, accurate method for identifying CD in the initial diagnostic biopsy of patients presenting with lymphocytic enteritis, even in seronegative patients, and seems to be better than anti-TG2 intestinal deposits.

Change of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion

Institute of Scientific and Technical Information of China (English)

Shi-Hua Zhou

2016-01-01

Objective:To analyze and investigate the change state of T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion. Methods: A total of 92 patients with recurrent spontaneous abortion in our hospital from June 2013 to July 2015 were selected as the observation group and 92 women with health delivery history at the same time were selected as the control group,then the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of two groups were detected and compared and the peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of patients with different gestational age at abortion and abortion times were compared too. Results:The peripheral blood T, B lymphocyte subsets and Th1/Th2 indexes of observation group and control group all had obvious differences,and those blood indexes levels' differences of patients with different gestational age at abortion and abortion times were obvious too, all P<0.05 and the differences were significant. Conclusions: The T, B lymphocyte subsets and Th1/Th2 indexes of patients with recurrent spontaneous abortion show abnormal state and the differences of detection results of patients with different gestational age at abortion and abortion times are relatively obvious,so those indexes should be monitored and improved intentinonally.

Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

International Nuclear Information System (INIS)

Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

1987-01-01

Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects

Studies of lymphocyte growth and differentiation. Progress report, September 1, 1975--July 31, 1976

Energy Technology Data Exchange (ETDEWEB)

Rubin, A.D.

1976-01-01

Studies were continued on ribonuclear protein synthesis and the assembly of ribosomes in resting and stimulated lymphocytes. We demonstrated the interdependency of protein synthesis and RNA synthesis in the formation and processing of nascent ribonuclear protein particles. We further explored lymphocyte nuclei in a cell-free system. By isolating lymphocyte chromatin we showed a direct effect of PHA on the ability of this nuclear structure to incorporate radioactivity into acid precipitable RNA. We returned to our previous studies on the delayed response of chronic lymphocytic leukemia (CLL) lymphocytes to PHA. We traced this alternate response identifying it as a characteristic of the CLL cell. The evidence questioned the generally accepted conclusion that CLL represents a B cell malignancy. We went on further to describe delayed reacting lymphocytes in the circulation of patients with nodular lymphoma and acute lymphoblastic leukemia (ALL). The ALL, unlike the lymphoma and CLL cells, showed a normal magnitude of response, even though it was delayed. We described the technique which might be employed as a diagnostic test for detecting abnormal lymphocytes in patients with lymphocytic lymphoma and leukemia and could help distinguish these diseases from benign lymphoid hyperplasia and other forms of non-lymphocytic leukemia.

Chromosomal sensitivity to X-rays in lymphocytes from patients with Turner syndrome

International Nuclear Information System (INIS)

Heras, J.G.; Coco, R.

1986-01-01

Lymphocytes from patients with Turner syndrome were irradiated with X-rays to determine the chromosomal aberration frequency in first-division metaphases. Five patients with 45,X karyotype; three 45,X/46,Xi(X)q mosaics; one 45,X/47,XXX mosaic and 9 female controls were studied. Patients with a 45,X karyotype exhibited a radioinduced chromosomal aberration frequency similar to controls. In the mosaics, 45,X cells has a mean frequency of 38.75 +- 2.16; 46,Xi(X)q cells a mean of 38 +- 2.16 and the control group a rate of 36.25 +- 4.32. No differences were observed between 45,X and 46,Xi(X)q cells, 45,X and normal cells or 46,Xi(X)q and normal cells. Apparently neither the X monosomy nor the Xq isochromosome influences the 'in vitro' X-ray-induced chromosomal damage in Turner syndrome lymphocytes. (Auth.)

CRUSTED SCABIES IN A PATIENT WITH ACUTE LYMPHOCYTIC LEUKEMIA

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Mamatha

2015-06-01

Full Text Available A 17 year s old male patient presented with diffuse, ill defined, hyperpigmented, scaly plaques on the body, for the past 15 days. Lesions were more over the groin and also on both elbows and wrists. Patient is a known case of acute lymphocytic leukaemia, diagnosed a t the age of 13 years and has been on treatment ever since. A KOH ( 10% mount of the scales showed the presence of sarcoptes scabiei and skin biopsy with haematoxylin and eosin showed fragments of mite in the excised skin.

Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes.

Science.gov (United States)

Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O'Connor, Timothy R

2017-01-01

Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much higher

Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes.

Directory of Open Access Journals (Sweden)

Sandrine Lacoste

Full Text Available Patients who undergo autologous hematopoietic stem cell transplantation (aHCT for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML. Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC, which is thought to influence the effect chemotherapeutic treatments have on the patient's stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA] are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER or nucleotide excision repair (NER. We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year. To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average, aHCT patients (both cases and controls showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was

Treatment strategy based on targeting P-glycoprotein on peripheral lymphocytes in patients with systemic autoimmune disease.

Science.gov (United States)

Tsujimura, Shizuyo; Tanaka, Yoshiya

2012-02-01

Although corticosteroids, immunosuppressants and disease-modifying antirheumatic drugs (DMARDs) are widely used in the treatment of various systemic autoimmune diseases such as systemic lupus erythematosus (SLE), we often experience patients with systemic autoimmune diseases who are resistant to these treatments. P-glycoprotein (P-gp) of membrane transporters, a product of the multiple drug resistance (MDR)-1 gene, is known to play a pivotal role in the acquisition of drug resistance to chemotherapy in malignancy. However, the relevance of MDR-1 and P-gp to resting and activated lymphocytes, which are the major target in the treatment of systemic autoimmune diseases, remains unclear. Studies from our laboratories found surface expression of P-gp on peripheral lymphocytes in patients with SLE and a significant correlation between the expression level and disease activity. Such expression is induced not only by genotoxic stresses but also by various stimuli including cytokines, resulting in active efflux of drugs from the cytoplasm of lymphocytes, resulting in drug-resistance and high disease activity. However, the use of both P-gp antagonists (e.g., cyclosporine) and inhibition of P-gp synthesis with intensive immunosuppressive therapy successfully reduces the efflux of corticosteroids from lymphocytes in vitro, suggesting that P-gp antagonists and P-gp synthesis inhibitors could be used to overcome drug-resistance in vivo and improve outcome. In conclusion, lymphocytes activated by various stimuli in patients with highly active disease apparently acquire MDR-1-mediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. The expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable target to combat drug resistance in patients with active systemic autoimmune diseases.

A comparative immunohistochemical and immunophenotypical study on lymphocytes expression in patients affected by oral lichen planus.

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Lorenzini, Guido; Viviano, Massimo; Chisci, Elettra; Chisci, Glauco; Picciotti, Maria

2013-09-01

Oral lichen planus (OLP) is an immune-mediated mucocutaneous disease of uncertain aetiology. OLP has many manifestations: reticular, erosive, atrophic, plaque like, papular, bullous, with unique etiopathogenetic working. The purpose of this study is to find a link between different clinical types of lichen and the alterations of lymphocytes on peripheral blood and oral mucosa. A total of 21 patients were enrolled in this study. The mean age of patients was 53.82 years, between 31 and 78 years. OLP Diagnosis was afterwards confirmed by histopathology. Selected patients underwent to clinical evaluation, lesion characterization, incisional biopsy, samples histological analysis, peripheral blood collection. Blood specimens were submitted to cell count determination with differential, characterization of populations and circulating lymphocyte subpopulations using monoclonal antibodies in flow cytometry. Referring to the clinical presentation of lesions, patients were divided in two groups: red lesions (RL) and white lesions (WL) and compared with an age-matched control group. The results of the immunophenotypic study showed correlation between WL and the expression of CD19 lymphocytes (r = 0.693, P = 0.0005). The results of immunohistochemical study performed on histological specimens showed a significant correlation between RL group and expression of all lymphocyte tested (CD3 r = 0.722 P = 0.0002, CD4 r = 0.579 P = 0.0060, CD56 r = 0.513 P = 0.0173, CD8 r = 0.548 P = 0.0102). We assume there is the responsibility of the expression of lymphocytes, not only type but also as quantity, in determining RL or WL manifestation of OLP. Circulating lymphocytes may have a role, too. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Occurrence of associated tumours in chronic lymphocytic leukemia].

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Szerafin, László; Jakó, János; Varju, Lóránt

2016-10-01

Chronic lymphocytic leukemia is one of the most common hematologic malignancy. The aim of the authors was to investigate the characteristics of malignancies associated with chronic lymphocytic leukemia in patients diagnozed between 2000 and 2015. Data of patients with chronic lymphocytic leukemia who had other associated tumours were analysed using the Leukemia/Lymphoma Registry of the Szabolcs-Szatmár-Bereg County, Hungary and patient records. Between January 1, 2000 and December 31, 2015, 526 patients with chronic lymphocytic leukemia were diagnosed. 95 patients of the 526 patients (18.06%) were diagnosed as having associated other tumours. In 48/95 patients (50.5%) the first diagnosed tumour was chronic lymphocytic leukemia, in 23/95 patients (24.2%) the first recognized malignancy was the associated tumour, whereas in 24/95 patients (25.3%) synchron tumours were diagnosed. The number of patients with more than one associated tumour was 10/95 (10.5%). The total number of tumours was 107. The incidence of chronic lymphoid leukemia increased in the period between 2000 and 2015 as compared to the period between 1983 and 1999 (3.19 vs 5.65/100 000 person/year). The occurrence of associated malignancies increased as well (8.06% vs 18.06%). In addition to the most common tumours (colorectal, breast, lung, prostate), skin squamous cell carcinoma (17/95 patients; 17.9%) and melanoma (6/95 patients; 6.3%) also frequently occurred. The second malignancies were most frequently discovered after the diagnosis of chronic lymphocytic leukemia and synchron tumours accounting for 78.5% (84/107) of all associated tumours. The incidence of second malignancies decreased 10 years after the diagnosis of chronic lymphocytic leukemia. The possible reasons for the high frequency of other tumours associated with chronic lymphocytic leukemia are elderly age of patients, immunsuppressed state and, presumably, chemotherapy of patients with chronic lymphocytic leukemia. During the follow up

Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

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Leonardo Rodrigues de Oliveira

2013-09-01

Full Text Available Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

Evaluation of platelet lymphocyte ratio and 90-day mortality in patients with acute exacerbation of chronic obstructive pulmonary disease.

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Kumar, Praneel; Law, Stephanie; Sriram, Krishna B

2017-06-01

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have high mortality and health care costs. The platelet to lymphocyte ratio (PLR) is a marker of inflammation and has been reported to be elevated in patients with AECOPD compared to stable state. In this study, we sought to evaluate the association of the PLR in patients with AECOPD with 90-day mortality. We conducted a retrospective cohort study of patients admitted to our institution with a primary diagnosis of AECOPD between January 2014 and July 2014. Blood test results on admission were recorded. The primary outcomes were 90-day mortality. One hundred and eighty-one AECOPD patients were considered for the study. Death had occurred in 16 (9%) patients within 90 days of hospital discharge. Univariable analysis identified age, haemoglobin, neutrophil count, and urea level, neutrophil lymphocyte ratio (NLR) and PLR as being associated with increased 90-day mortality. Multivariable logistic regression analysis variables demonstrated that only PLR (P=0.03) was significantly associated with death at 90 days. Receiver operator characteristic analysis identified PLR ≥235 had a sensitivity of 63% and specificity of 74% in predicting 90-day mortality. PLR was ≥235 was also associated with worse survival (days) [mean ± standard deviation (SD): PLR ≥235 vs. PLR <235: 512±358 vs. 626±346, P=0.004]. A PLR ≥235 was significantly associated with 90-day mortality, which may provide prognostic guidance to clinicians.

Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma

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Chen, Xue; Zhang, Yang; Wang, Fang; Wang, Mangju; Teng, Wen; Lin, Yuehui; Han, Xiangping; Jin, Fangyuan; Xu, Yuanli; Cao, Panxiang; Fang, Jiancheng; Zhu, Ping; Tong, Chunrong; Liu, Hongxing

2017-01-01

Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc-13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X-linked ...

The effects of radioiodine therapy on peripheral blood lymphocyte subpopulations in patients with Graves' disease. Preliminary report

International Nuclear Information System (INIS)

Turowska, M.D.; Rogowski, F.; Turowski, D.; Wysocka, J.

2002-01-01

Treatment of Graves' disease patients with radioactive iodide ( 131 I) is becoming the standard therapy in an increasing group of cases but can induce alterations in immune response, like increasing levels of thyroid autoantibodies, and, in part, exacerbation of ophthalmopathy. The aim of this study was to assess the changes in peripheral blood (PB) lymphocyte subpopulations after 131 I treatment of patients with Graves' disease. The study was carried out in a group of 30 patients with Graves' disease (23 f; 7 m) 49.5±10.0 years of age, 26 with different subjective ocular signs like gritty sensation, increased lacrimation, orbital pain, and exophthalmos. PB lymphocyte subsets were analysed by cytofluorometry, serum concentration of TSH and fT4 were evaluated before and 6 weeks after radioiodine treatment. After 131 I treatment a significant increase in CD3+, CD4+, CD3+HLA-DR+ and a decrease in CD19+ percentages of lymphocyte subsets were found in comparison with the initial evaluation. No significant changes in percentage of CD8+ and NK (CD3-CD16+ CD56+) cells were observed during this study. A significant increase in TSH and a slight decrease in fT4 concentration concentration took place in the 6th week after 131 I application. The patients without subjective improvement of ocular signs during the therapy initially had a percentage of CD3+, CD8+ lymphocytes which was significantly lower compared with those with regression of ocular signs observed after 131 I treatment. The changes in PB lymphocyte subsets caused by 131 I treatment of Graves' disease confirm the involvement of acquired cellular immunity after radiation damage of the thyroid gland. The decreased initial percentage of CD8+ and CD3+ lymphocytes could help make a prediction of ocular symptoms persisting after radioiodine treatment in some patients with ophthalmopathy. (author)

Effect of radiation on cell-mediated cytotoxicity and lymphocyte subpopulations in patients with ovarian carcinoma

International Nuclear Information System (INIS)

Kohorn, E.I.; Mitchell, M.S.; Dwyer, J.M.; Knowlton, A.H.; Klein-Angerer, S.

1978-01-01

Lymphocyte subpopulations and cell-mediated cytotoxicity (CMI) were studied during radiation therapy in 16 patients with ovarian carcinoma. The total lymphocyte count became depressed in all patients. The depression was more marked among T cells, while the proportion of B cells remained unaffected. In patients with Stage I and II ovarian cancer, CMI was depressed significantly by radiotherapy after 7 days of treatment, remained low at 14 days but recovered despite continuation of radiation. This depression of CMI occurred at a delivered dose of 1,000 rads with subsequent recovery. Patients with Stage III ovarian cancer given pelvic and abdominal radiation were found to have no consistent depression of CMI, a finding similar to that in Stage III ovarian carcinoma patients given chemotherapy

Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

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Toge, T; Hamamoto, S; Itagaki, E; Yajima, K; Tanada, M; Nakane, H; Kohno, H; Nakanishi, K; Hattori, T

1983-11-01

In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

Effect of Smoking on Peripheral Blood Lymphocyte Subsets of Patients With Chronic Renal Failure.

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Düvenci Birben, Özlem; Akçay, Şule; Sezer, Siren; Şirvan, Şale; Haberal, Mehmet

2016-11-01

Smoking is known to suppress the immune system. It is also known that chronic renal failure affects the immune system. However, the number of studies investigating the effects of chronic renal failure and smoking together is limited. In our study, we examined whether smoking affects the diminished response of the immune system in patients with chronic renal failure. We compared peripheral blood lymphocyte subsets in smoking and nonsmoking patients with chronic renal failure. We also used the Fagerström Test for Nicotine Dependence to evaluate its correlation with the lymphocyte subset count in patients who are current smokers. Our study included 126 patients with chronic renal failure. According to their smoking habits, patients were divided into 2 groups: smokers and nonsmokers. The average age of patients who were smokers was 53.2 ± 1.5 years, with average age of nonsmokers being 59.2 ± 2.2 years. The average duration of smoking in smokers was 30.7 ± 2.7 packyears. We found that the percentage of cluster of differentiation 16-56 cells (natural killer cells) and lymphocyte percentage were significantly lower among smokers in our study (P chronic renal failure, similar to that shown in healthy smokers. According to our findings, patients with chronic renal failure, where infection is the primary reason for mortality and morbidity, must be questioned for smoking and referred to smoking cessation clinics. Because of its immunosuppressive effects, smoking behaviors must be solved preoperatively in transplant candidates.

Effect of radiotherapy on lymphocyte subpopulations in patients with carcinoma of the breast and uterine cervix

International Nuclear Information System (INIS)

Guha Thakurta, S.; De, M.; Roy Chowdhury, J.

1983-01-01

Immune competence was evaluated in 43 patients of carcinoma breast, 77 patients of cancer cervix, as compared to 30 normal healthy women. The study also included 25 women from the two carcinoma groups, who had undergone radiotherapy. A reduction in the white blood cell count, absolute lymphocyte count, active T-cell count and absolute T-cell count were observed in patients with carcinoma of the breast and cervix prior to irradiation. Radiation therapy resulted in a striking reduction of all the three parameters in both the carcinoma groups. Substantial recovery was observed within a year after cessation of therapy. Increased number of peripheral B lymphocytes was observed in carcinoma of the breast as well as the cervix prior to irradiation. At completion of radiation, the number decreased markedly in both groups of patients. Gradual recovery took place within a year. The reduction in lymphocyte numbers and its subpopulations could not be attributed to thymic irradiation, since patients receiving pelvic and mediastinal (including thymic) radiotherapy showed similar changes. (author)

Detection of radioiodine-induced cytogenetic alterations in circulating lymphocytes of thyroid patients

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Kasuba, V [Inst. for Medical Recearch and Occupational Health, Zagreb (Croatia). Laboratory for Mutagenesis; Konrady, A; Koeteles, G J [Frederic Joliot-Curie National Research Institute for Radiobiology and Radiohygiene, Budapest (Hungary); Kusic, Z [Clinical Hospital Sestre Milosrdnice, Zagreb (Croatia). Dept. of Oncology and Nuclear Medicine

1994-10-01

Radioiodines are often used for experimental purposes and for diagnosis and therapy in clinical practice. Human population might also be exposed to radioiodines in nuclear accidents. The ionizing energy of radioiodine affects not only the thyroid where it concentrates but also other tissues, especially the lymphocytes during their circulation through and around the gland containing the radioisotopes. Therefore, it seemed to be of interest to carry out investigations concerning the cytogenetic alterations in blood lymphocytes of patients treated with iodine-131. The method of choice was the relatively easily performable micronucleus assay in cytokinesis-blocked cultures of human peripheral lymphocytes. The test was performed on blood samples of 30 patients before the radioisotope treatment and one, two and four days after, one as well as 6 and - in a few cases - 12 weeks later. The amounts of iodine-131 injected were dependent on the clinical practices to reach the therapeutic radiation doses for hyperthyroidism and adenomas and were in the range of 220 and 5180 MBq. it was observed that the micronucleus frequency increased in the treated hyperthyroid patients while in patients with toxic adenomas the radioiodine did not result in an increase or even as compared to the pretreatment values in a few cases decreased values were seen. The results suggest individual differences in radiosensitivity as well as that the frequency of cytogenetic alterations depend on the physiological or pathological conditions of the thyroid. The significance of this observation will be discussed for dose assessments by cytogenetic techniques due to internal radioiodine. (author).

Chromosomal sensitivity to X-rays in lymphocytes from patients with Turner syndrome

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Heras, J G; Coco, R

1986-03-01

Lymphocytes from patients with Turner syndrome were irradiated with X-rays to determine the chromosomal aberration frequency in first-division metaphases. Five patients with 45,X karyotype; three 45,X/46,Xi(X)q mosaics; one 45,X/47,XXX mosaic and 9 female controls were studied. Patients with a 45,X karyotype exhibited a radioinduced chromosomal aberration frequency similar to controls. In the mosaics, 45,X cells has a mean frequency of 38.75 +- 2.16; 46,Xi(X)q cells a mean of 38 +- 2.16 and the control group a rate of 36.25 +- 4.32. No differences were observed between 45,X and 46,Xi(X)q cells, 45,X and normal cells or 46,Xi(X)q and normal cells. Apparently neither the X monosomy nor the Xq isochromosome influences the in vitro X-ray-induced chromosomal damage in Turner syndrome lymphocytes. (Auth.). 29 references, 4 tables.

Basal and T₃-induced ROS production in lymphocyte mitochondria is increased in type 2 diabetic patients

DEFF Research Database (Denmark)

Anthonsen, S; Larsen, J; Pedersen, P L

2013-01-01

in human lymphocytes in patients with diabetes mellitus type 2 (T2DM). Lymphocytes from 10 controls and 10 persons with T2DM were examined. Mitochondrial membrane potential (MMP) was examined by flow cytometry after staining with MitoTracker Green (MTG). Similarly ROS was measured following staining...

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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Mark Bustoros

2018-04-01

Full Text Available BackgroundPrimary extranodal marginal zone lymphoma (MZL of the dura is a rare neoplastic entity in the central nervous system (CNS.MethodsWe used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma (SLL.ResultsWe identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes.ConclusionPrimary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.

[Chromosome banding analysis of peripheral blood lymphocytes stimulated with IL2 and CpG oligonucleotide DSP30 in patients with chronic lymphocytic leukemia].

Science.gov (United States)

Stěpanovská, K; Vaňková, G; Némethová, V; Tomášiková, L; Smuhařová, P; Divíšková, E; Vallová, V; Kuglík, P; Plevová, K; Oltová, A; Doubek, M; Pospíšilová, S; Mayer, J

2013-01-01

Chromosomal aberrations play an important role as prognostic factors in chronic lymphocytic leukemia (CLL). These aberrations are mostly detected by fluorescent in situ hybridization (FISH), as chromosomal banding analysis has been scarce due to low proliferative activity of malignant B-lymphocytes in vitro. In 2006, a new method using stimulation with IL-2 and CpG oligonucleotide DSP30 for metaphase generation in CLL was published [1]. The objective of our study was to verify the efficacy of stimulation and to evaluate if the method is suitable for routine diagnostics. In total, peripheral blood samples of 369 CLL patients were analyzed in parallel by chromosomal banding analysis and by FISH probes for 13q14, 11q22-23, CEP12 and 17p13. Out of 369 patients, 307 (83%) were successfully stimulated for metaphase generation. Chromosomal aberrations were detected in 243 (79%) out of 307 patients evaluated by chromosomal banding analysis. Other aberrations that are not included into standard FISH panel were detected in patients karyotypes, e.g. del(6q), del(14q), t(14;18)(q32;q21), t(11;14)(q13;q32) and t(18;22)(q21;q11). One hundred and three (42%) patients showed complex aberrant karyotype not detected by FISH analysis. Stimulation with IL-2 and oligonucleotide DSP30 is an efficient method how to induce proliferation of malignant B-lymphocytes and allows detection of a substantial number of chromosomal aberrations in addition to those detected by standard FISH panel. Using this method in routine diagnostics is helpful particularly in identification of patients with complex aberrant karyotype.

Sensitivity of T lymphocytes to gamma rays in patients with cervix tumor

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Oueslati, R; Kdous, CH; Chouikha, M [Lab. Immunology, Hopital de Tunis, (Tunisia); Maalej, M; Kochbati, N [Service Radiotherapy, Institut Salah Azeiz, (Tunisia)

1995-10-01

In this work we studied the effect of radiotherapy on normal cells in patients with cervix tumors treated only by gamma rays. In our laboratory, after lymphocytes separation, we tested the proliferation system of these cells against the phytohemagglutinin and the concanavalin a antigens; at the same time we tested their sensitivity to lys the erythroid tumor cells line K 562. According to the clinical stage of disease the 25 patients studied were divided in two groups; group I composed of 14 patients at stage I and II proximal, received 50 Gy from a cesium 137 source, in intrauterine and in continuous treatment during 4 days. The second group composed of 11 patients at stage II distal and III, received 50 Gy from a cobalt-60 source in extra uterine, the treatment is fractioned in 3 to 5 times per week, at each time the patient received 1,5 - 3 Gy. To compare with their immunological status before treatment, until 1 month after total dose received, all of our patients lost transitory their capacity to prolifere in vitro. Although the capacity to lys the tumor cells is diminished in cancer patients, the drop of this activity is principally. The selective recuperation of T lymphocytes stimulated by concanavalin A is also observed. 3 figs., 2 tabs.

Sensitivity of T lymphocytes to gamma rays in patients with cervix tumor

International Nuclear Information System (INIS)

Oueslati, R.; Kdous, CH.; Chouikha, M.; Maalej, M.; Kochbati, N.

1995-01-01

In this work we studied the effect of radiotherapy on normal cells in patients with cervix tumors treated only by gamma rays. In our laboratory, after lymphocytes separation, we tested the proliferation system of these cells against the phytohemagglutinin and the concanavalin a antigens; at the same time we tested their sensitivity to lys the erythroid tumor cells line K 562. According to the clinical stage of disease the 25 patients studied were divided in two groups; group I composed of 14 patients at stage I and II proximal, received 50 Gy from a cesium 137 source, in intrauterine and in continuous treatment during 4 days. The second group composed of 11 patients at stage II distal and III, received 50 Gy from a cobalt-60 source in extra uterine, the treatment is fractioned in 3 to 5 times per week, at each time the patient received 1,5 - 3 Gy. To compare with their immunological status before treatment, until 1 month after total dose received, all of our patients lost transitory their capacity to prolifere in vitro. Although the capacity to lys the tumor cells is diminished in cancer patients, the drop of this activity is principally. The selective recuperation of T lymphocytes stimulated by concanavalin A is also observed. 3 figs., 2 tabs

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

OpenAIRE

Mélanie Saint-Jean; Anne-Chantal Knol; Christelle Volteau; Gaëlle Quéreux; Lucie Peuvrel; Anabelle Brocard; Marie-Christine Pandolfino; Soraya Saiagh; Jean-Michel Nguyen; Christophe Bedane; Nicole Basset-Seguin; Amir Khammari; Brigitte Dréno

2018-01-01

Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs). This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2) regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous ...

Lymphocytic Pleural Effusion in Acute Melioidosis

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Kuo-Mou Chung

2007-10-01

Full Text Available An endemic outbreak of melioidosis developed in southern Taiwan following a flood caused by a typhoon in July 2005. A total of 27 patients were diagnosed with the acute and indigenous form of pulmonary melioidosis. Parapneumonic pleural effusions were noted on chest X-rays in six patients. Thoracentesis was done in three patients and all revealed lymphocyte predominance in differential cell count. Burkholderia pseudomallei was isolated in the pleural effusion in one of them. All three patients survived after antibiotic treatment. Lymphocytic pleural effusion is generally seen in tuberculosis or malignancy. However, our findings suggest that melioidosis should be considered in the differential diagnosis of lymphocytic pleural effusion.

An improved method on stimulated T-lymphocytes to functionally characterize novel and known LDLR mutations[S

Science.gov (United States)

Romano, Maria; Di Taranto, Maria Donata; Mirabelli, Peppino; D'Agostino, Maria Nicoletta; Iannuzzi, Arcangelo; Marotta, Gennaro; Gentile, Marco; Raia, Maddalena; Di Noto, Rosa; Del Vecchio, Luigi; Rubba, Paolo; Fortunato, Giuliana

2011-01-01

The main causes of familial hypercholesterolemia (FH) are mutations in LDL receptor (LDLR) gene. Functional studies are necessary to demonstrate the LDLR function impairment caused by mutations and would be useful as a diagnostic tool if they allow discrimination between FH patients and controls. In order to identify the best method to detect LDLR activity, we compared continuous Epstein-Barr virus (EBV)-transformed B-lymphocytes and mitogen stimulated T-lymphocytes. In addition, we characterized both novel and known mutations in the LDLR gene. T-lymphocytes and EBV-transformed B-lymphocytes were obtained from peripheral blood of 24 FH patients and 24 control subjects. Functional assays were performed by incubation with fluorescent LDL followed by flow cytometry analysis. Residual LDLR activity was calculated normalizing fluorescence for the mean fluorescence of controls. With stimulated T-lymphocytes we obtained a better discrimination capacity between controls and FH patients compared with EBV-transformed B-lymphocytes as demonstrated by receiver operating characteristic (ROC) curve analysis (the areas under the curve are 1.000 and 0.984 respectively; P < 0.0001 both). The characterization of LDLR activity through T-lymphocytes is more simple and faster than the use of EBV-transformed B-lymphocytes and allows a complete discrimination between controls and FH patients. Therefore the evaluation of residual LDLR activity could be helpful not only for mutation characterization but also for diagnostic purposes. PMID:21865347

[Increased expressions of peripheral PD-1+ lymphocytes and CD4+CD25+FOXP3+ T cells in gastric adenocarcinoma patients].

Science.gov (United States)

Li, Hao; Li, Songyan; Hu, Shidong; Zou, Guijun; Hu, Zilong; Wei, Huahua; Wang, Yufeng; Du, Xiaohui

2017-01-01

Objective To detect the frequencies of peripheral programmed death-1 + (PD-1 + ) lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in patients with gastric adenocarcinoma. Methods The study enrolled 29 patients with gastric adenocarcinoma and 29 age- and sex-matched healthy controls. Frequencies of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells were detected using flow cytometry. Results The number of PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood was higher in patients with gastric adenocarcinoma than that in the control group. Moreover, linear correlation analysis indicated a positive correlation between PD-1 expression and frequency of CD4 + CD25 + FOXP3 + regulatory T cells in peripheral blood of the patients. Conclusion Gastric adenocarcinoma patients present with increased PD-1 + lymphocytes and CD4 + CD25 + FOXP3 + regulatory T cells in the peripheral blood.

Laboratorial diagnosis of lymphocytic meningitis

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Sérgio Monteiro de Almeida

Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

The relationship between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with obstructive sleep apnea syndrome

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Hülya Günbatar

2015-09-01

Full Text Available Objective: There is a strong relationship between obstructive sleep apnea syndrome (OSAS and cardiovascular disease (CVD. Chronic intermittent hypoxia, inflammation, oxidative stress, and endothelial dysfunction may create etiologic mechanisms, connection between OSAS to CVD. Inflammation play an important role in the development of CVD. Platelet- Lymphocyte Ratio (PLR and Neutrophil-lymphocyte Ratio (NLR are new biomarkers showing inflammation. This study was designed to investigate the association between PLR, NLR and relationship between severity of OSAS, polysomnographic parameters and PLR. Methods: This was a cohort study in which patients who had undergone a full night polysomnography for diagnosis of OSA were recruited. Patients were divided according to their apnea hypopnea index (AHI scores into OSAS negative simple snoring (Group 1; AHI 30 groups. Results: A total of 111 patients were included in this study. There were 26, 22 and 63 patients in Groups 1, 2 and 3, respectively. PLR were significantly different between groups (Group 1: 87.12, Group 2: 103.6, Group 3: 112.5, p < 0.05. PLR were significantly correlated with NLR, AHI, oxygen desaturation index, average and minimum O2 saturation values (p < 0.05. Multiple regression analysis demonstrated that PLR is an independent predictor of CVD. PLR cut-off value for demonstrating the presence of CVD is higher than 86.03. Conclusion: In the light of these findings, PLR is strongly associated with the severity of OSAS. PLR might be used as a biomarker to predict CVD in OSAS patients.

The ratio Neutrophil/Lymphocyte and Platelet/Lymphocyte in patient with Rheumatoid Arthritis that are Treating with Anti-TNF

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İsmail Boyraz

2014-06-01

Full Text Available OBJECTIVES: Rheumatoid arthritis (RA is a chronic inflammatory disorder with unknown etiology. RA is characterized by a variable course of remissions and relapses, and subclinical inflammation persists between the disease exacerbations. Anti-TNF therapies have become more often preferred in recent years in the treatment of RA. The aim of the present study was to determine the relationship between N/L and P/L ratios and subclinical inflammation in patients with RA who achieved remission with anti-TNF therapy. METHODS: The present study was a retrospective, controlled and multicenter study. The present study reviewed the medical records of the patients who were on follow-up in the outpatient clinics of the Department of Physical Therapy in Abant İzzet Baysal University and Harran University due to rheumatoid arthritis (RA and who achieved remission with anti-TNF therapy.A total of 80 patients in the inactive phase of RA and 45 healthy subjects in the control group were included in the study. Hemogram results of the people were examined retrospectively. RESULTS: There was significant difference between the patient and the control group in terms of platelet ratio and lymphocyte and neutrophil ratio. There was no significant difference between the group in terms of N/L and P/L ratios.CONCLUSIONS:  In the current study, we found significant differences between the patient and the control group in terms of neutrophil, lymphocyte, and platelet counts; however, there was no significant difference between the two groups in terms of N/L and P/L ratios. These findings suggest that therapies with anti-TNF agents in patients with RA achieved complete control of inflammation. 

Ibrutinib as an antitumor immunomodulator in patients with refractory chronic lymphocytic leukemia

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Cubillos-Zapata, Carolina; Avendaño-Ortiz, Jose; Córdoba, Raúl; Hernández-Jiménez, Enrique; Toledano, Victor; Pérez de Diego, Rebeca; López-Collazo, Eduardo

2016-01-01

Ibrutinib has emerged as a promising therapy for patients with chronic lymphocytic leukemia (CLL) who are nonresponsive to standard therapies. The refractory state of monocytes and T-cell exhaustion in patients with CLL could explain the morbidity and mortality reported in these patients. We studied the effect of ibrutinib on the immune response of four relapsed patients with CLL during the first treatment cycle. We observed the ability to recover the standard response against bacterial stimu...

Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

Science.gov (United States)

Liu, X; Liu, H; Guo, Z; Luan, W

2006-01-01

To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

Elevated neutrophil-lymphocyte ratio in patients with euthyroid chronic autoimmune thyreotidis

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Keskin Havva

2016-07-01

Full Text Available Objective. The neutrophil-lymphocyte ratio (NLR, determined from peripheral blood, is accepted as an available and practical indicator of the systemic inflammation. In this study, we aimed to determine whether the NLR was higher in euthyroid chronic autoimmune thyreotidis (CAT patients compared to a healthy control group.

Enhancing effects of thymopoietin and T cell growth factor on mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia

International Nuclear Information System (INIS)

Knox, S.J.; Greenberg, B.R.; Anderson, R.W.; Shifrine, M.

1983-01-01

Cloning efficiencies and mitogenic responsiveness of lymphocytes from patients with preleukemic disorders are significantly depressed compared to normal values. TP-5 and IL-2 markedly increased the cloning efficiency and mitogenic responsiveness of lymphocytes from many of the preleukemic patients studied, while there was little or no effect in control cultures. Enhancement of lymphocyte responsiveness with TP-5 and IL-2 suggests the presence of maturational/-functional defects in these patients which may be compensated for in part by addition of TP-5 and IL-2

Preoperative lymphocyte-to-monocyte ratio represents a superior predictor compared with neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios for colorectal liver-only metastases survival

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Peng JH

2017-07-01

Full Text Available Jianhong Peng,1,* Hui Li,2,* Qingjian Ou,1,* Junzhong Lin,1 Xiaojun Wu,1 Zhenhai Lu,1 Yunfei Yuan,1 Desen Wan,1 Yujing Fang,1 Zhizhong Pan1 1Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Systemic inflammation was recognized as an essential factor contributing to the development of malignancies. This study aimed to investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR, neutrophil-to-lymphocyte ratio (NLR, and platelet-to-lymphocyte ratio (PLR in patients with colorectal liver-only metastases (CLOM undergoing hepatectomy. We retrospectively enrolled 150 consecutive patients with CLOM between 2000 and 2012. The optimal cutoff values of continuous LMR, NLR, and PLR were determined using the receiver operating characteristic curve analysis. Recurrence-free survival (RFS and overall survival (OS related to the LMR, NLR, and PLR were analyzed using both Kaplan–Meier and multivariate Cox regression methods. Elevated LMR (≥2.82 and lower NLR (<4.63 were significantly associated with better RFS and OS in patients with CLOM after hepatectomy, instead of lower PLR (<150.17. Multivariate Cox analysis identified elevated LMR as the only independent inflammatory factor for better RFS (hazard ratio, 0.591; 95% CI, 0.32–0.844; P=0.008 and OS (hazard ratio, 0.426; 95% CI, 0.254–0.716; P=0.001. In the subgroup analysis, elevated LMR was a significant favorable factor in both 5-year RFS and OS of patients with male gender, lymph node metastases, colon cancer, liver tumor with the largest diameter <5 cm, preoperative carcinoembryonic antigen level <200 ng/mL, negative hepatitis B virus infection, non

Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma

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Feng JF

2013-11-01

Full Text Available Ji-Feng Feng,1 Ying Huang,2 Jin-Shi Liu1 1Department of Thoracic Surgery, 2Department of Operating Theatre, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China Background: Recent studies have shown that the presence of systemic inflammation correlates with poor survival in various types of cancers. This study investigated the usefulness of a novel inflammation-based prognostic system, using the combination of neutrophil lymphocyte ratio (NLR and platelet lymphocyte ratio (PLR, collectively named the CNP, for predicting survival in patients with esophageal squamous cell carcinoma (ESCC. Materials and methods: The CNP was calculated on the basis of data obtained on the day of admission: patients with both elevated NLR (>3.45 and PLR (>166.5 were allocated a score of 2, and patients showing one or neither were allocated a score of 1 or 0, respectively. Results: The CNP was associated with tumor length (P<0.001, differentiation (P=0.021, depth of invasion (P<0.001, and nodal metastasis (P<0.001. No significant differences were found between the CNP and morbidity. However, significant differences were found between the CNP and mortality (P<0.001. The overall survival in the CNP 0, CNP 1, and CNP 2 groups were 63.4%, 50.0%, and 20.2%, respectively (CNP 0 versus CNP 1, P=0.014; CNP 1 versus CNP 2, P<0.001. Multivariate analyses showed that CNP was a significant predictor of overall survival. CNP 1–2 had a hazard ratio (HR of 1.964 (95% confidence interval [CI]: 1.371–2.814, P<0.001 for overall survival. CNP (HR =1.964, P<0.001 is superior to NLR (HR =1.310, P=0.053 or PLR (HR =1.751, P<0.001 as a predictive factor. Conclusion: The CNP is considered a useful predictor of postoperative survival in patients with ESCC. The CNP is superior to NLR or PLR as a predictive factor in patients with ESCC. Keywords: esophageal squamous cell carcinoma (ESCC, neutrophil lymphocyte ratio (NLR, platelet lymphocyte ratio (PLR, overall survival

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

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Ellebaek Eva

2012-08-01

Full Text Available Abstract Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL, in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625 including patients with metastatic melanoma, PS ≤1, age Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months, 2 patients had stable disease (4 and 5 months and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.

Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia.

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Aslan, Mehmet; Horoz, Mehmet; Kocyigit, Abdurrahim; Ozgonül, Saadet; Celik, Hakim; Celik, Metin; Erel, Ozcan

2006-10-10

Oxidant stress has been shown to play an important role in the pathogenesis of iron deficiency anemia. The aim of this study was to investigate the association between lymphocyte DNA damage, total antioxidant capacity and the degree of anemia in patients with iron deficiency anemia. Twenty-two female with iron deficiency anemia and 22 healthy females were enrolled in the study. Peripheral DNA damage was assessed using alkaline comet assay and plasma total antioxidant capacity was determined using an automated measurement method. Lymphocyte DNA damage of patients with iron deficiency anemia was significantly higher than controls (ptotal antioxidant capacity was significantly lower (ptotal antioxidant capacity and hemoglobin levels (r=0.706, ptotal antioxidant capacity and hemoglobin levels were negatively correlated with DNA damage (r=-0.330, p<0.05 and r=-0.323, p<0.05, respectively). In conclusion, both oxidative stress and DNA damage are increased in IDA patients. Increased oxidative stress seems as an important factor that inducing DNA damage in those IDA patients. The relationships of oxidative stress and DNA damage with the severity of anemia suggest that both oxidative stress and DNA damage may, in part, have a role in the pathogenesis of IDA.

Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

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Famenini, Shannon; Martires, Kathryn J; Zhou, Hui; Xavier, Marin F; Wu, Jashin J

2015-01-01

The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern California patients. The mortality of patients with melanoma was examined using Cox proportional hazards modeling. The age-adjusted incidence rate per 100,000 person-years for melanoma among patients with either CLL or NHL was 107 (95% confidence interval 84.4-129.6) versus 25.9 among the general population (95% confidence interval 84.4-129.6, P < .001). Patients with melanoma and a history of CLL or NHL had 2.46 greater odds of death compared with those without CLL or NHL (95% confidence interval 1.77-3.41). This study was retrospective in nature; the International Classification of Diseases, Ninth Revision codes used may contain diagnostic errors; and only overall survival was used in our analysis. Patients with a history of CLL or NHL have a higher incidence of melanoma. Patients with CLL or NHL who are subsequently given the diagnosis of melanoma have a higher mortality than patients with melanoma without a preceding diagnosis of CLL. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Higher plasma CD4 lymphocyte count correlates with better cognitive function in human immunodeficiency virus-acquired immunodeficiency syndrome (HIV-AIDS) patients

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Fitri, F. I.; Rambe, A. S.; Fitri, A.

2018-03-01

Neurocognitive disorders in HIV-AIDS are still prevalent despite the use of antiretroviral therapy and seem to be under-recognized. Plasma lymphocyte CD4 count is a marker for general immunology status, but its association with cognitive function remains unclear. The aim of this study was to determine the correlation between plasma CD4 lymphocyte and cognitive function in HIV-AIDS patients.This was a cross-sectional study involving 48 HIV-AIDS patients. All subjects underwent physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts.This study included 48 subjects consisted of 29 males (60.4%) and 19 females (39.6%). The mean age was 39.17±11.21 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r=0.347, p=0.016).Higher plasma CD4 lymphocyte count is correlated with better cognitive function in HIV-AIDS patients.

Increased Incidence of T-Cell Malignancies in Patients with Chronic Lymphocytic Leukemia

OpenAIRE

Choi, Goda; van den Broek, Esther C; Stam, Olga CG; van Noesel, C.J.M.; Tonino, Sanne H.; Kater, Armon P.

2015-01-01

We present a patient with chemotherapy-refractory Chronic Lymphocytic Leukemia (CLL) in whom postmortem examination showed hepatosplenomegaly, with both multiple small-cellular CLL lesions and large-cellular, monoclonal T-cell infiltrates. Following this case, the co-incidence of T-cell malignancies and CLL was studied using Dutch and American cancer registry databases. Analysis showed an excess risk for T-cell malignancies in CLL patients, with increased standardized incidence ratios compare...

Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

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Márcia Antoniazi Michelin

2015-03-01

Full Text Available Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+ lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN. We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

Circulating Lymphocyte Subsets 
in Patients with Lung Cancer and Their Prognostic Value

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Jun LUO

2011-08-01

Full Text Available Background and objective Lung cancer is one of the most common malignancies. The aim of this study is to investigate the relationship between the change of lymphocyte subsets in the peripheral blood of lung cancer patients and the survival rate. Methods Flow cytometry was used to measure the percentages of lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells in peripheral blood obtained from 221 patients with primary lung cancer without any treatment and from 96 healthy blood donors as the control group. The result was combined with clinical and follow-up data and statistical analysis was conducted. Results The levels of CD3+ and CD8+ in the patient group are significantly lower compared with the control group, whereas the levels of CD4+/CD8+, CD19+, CD25+, CD44+, and NK cells are significantly higher (P<0.05. CD8+ is significantly higher in the small cell lung cancer (SCLC group compared with the non-small cell lung cancer (NSCLC group. However, CD4+ and CD4+/CD8+ are lower in SCLC (P<0.05. There were no significant differences in different stages and differentiation (P>0.05 in the NSCLC group. The level of CD3+ was significantly higher compared with the pre-chemotherapy group, but NK cell, CD19+, and CD44+ were distinctly lower in the post-chemotherapy group (P<0.05. More survival opportunities will be obtained for patients with no increase in CD44+ after chemotherapy (P=0.021, but the other three indices have no obvious influence on survival. Conclusion Widespread changes of lymphocyte occur in the peripheral blood of patients with lung cancer. There is a significant correlation between the change of CD44+ and the prognosis after chemotherapy.

Growth of human T lymphocyte colonies from whole blood: culture requirements and applications

International Nuclear Information System (INIS)

Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.

1982-01-01

Growth of human lymphocyte colonies from whole blood following stimulation with PHA, Con A, or PPD is described. Individual colony cells were identified as T lymphocytes on the basis of surface marker and enzyme cytochemical characterizations. Colony formation increased as a power function over a wide range of cell concentrations above a critical minimal concentration. The whole blood culture system eliminates possible selective effects of lymphocyte colony techniques utilizing gradient-enriched lymphocyte fractions and more closely approximates the in vivo milieu. The whole blood colony method is more sensitive for the detection of low-level radiation effects on lymphocytes than widely used tests that measure 3 H-thymidine incorporation. In preliminary studies, researchers used the whole blood method to determine the relative radiosensitivity of lymphocytes from humans with various hematopoietic disorders, and observed abnormalities in mitogen responsiveness and colony formation in some of the patient groups. This method has wide application for studies in cellular and clinical immunology

Characterizing T Cells in SCID Patients Presenting with Reactive or Residual T Lymphocytes

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Atar Lev

2012-01-01

Full Text Available Introduction. Patients with severe combined immunodeficiency (SCID may present with residual circulating T cells. While all cells are functionally deficient, resulting in high susceptibility to infections, only some of these cells are causing autoimmune symptoms. Methods. Here we compared T-cell functions including the number of circulating CD3+ T cells, in vitro responses to mitogens, T-cell receptor (TCR repertoire, TCR excision circles (TREC levels, and regulatory T cells (Tregs enumeration in several immunodeficinecy subtypes, clinically presenting with nonreactive residual cells (MHC-II deficiency or reactive cells. The latter includes patients with autoreactive clonal expanded T cell and patients with alloreactive transplacentally maternal T cells. Results. MHC-II deficient patients had slightly reduced T-cell function, normal TRECs, TCR repertoires, and normal Tregs enumeration. In contrast, patients with reactive T cells exhibited poor T-cell differentiation and activity. While the autoreactive cells displayed significantly reduced Tregs numbers, the alloreactive transplacentally acquired maternal lymphocytes had high functional Tregs. Conclusion. SCID patients presenting with circulating T cells show different patterns of T-cell activity and regulatory T cells enumeration that dictates the immunodeficient and autoimmune manifestations. We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency.

Neutrophil-to-lymphocyte ratio as an independent predictor for survival in patients with localized clear cell renal cell carcinoma after radiofrequency ablation: a propensity score matching analysis.

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Chang, Xiaofeng; Zhang, Fan; Liu, Tieshi; Wang, Wei; Guo, Hongqian

2017-06-01

To investigate the role of neutrophil-to-lymphocyte ratio as a prognostic indicator in patients with localized clear cell renal cell carcinoma treated with radiofrequency ablation. We retrospectively analyzed data from patients with renal cell carcinoma who underwent radiofrequency ablation from 2006 to 2013. The Kaplan-Meier method was used to generate the survival curves according to different categories of neutrophil-to-lymphocyte ratio. Relationships between preoperative neutrophil-to-lymphocyte ratio or the change of neutrophil-to-lymphocyte ratio and survival were evaluated with multivariable Cox proportional hazards regression analysis. A propensity score matching analysis was carried out to avoid confounding bias. A total of 185 patients were included in present study. When stratified by preoperative neutrophil-to-lymphocyte ratio cutoff value of 2.79, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio analysis, 5-year recurrence-free survival, 5-year disease-free survival, and 5-year overall survival rates of neutrophil-to-lymphocyte ratio ratio with the change of neutrophil-to-lymphocyte ratio, patients with both preoperative neutrophil-to-lymphocyte ratio ≥2.79 and the change of neutrophil-to-lymphocyte ratio ≥0.40 had the worst disease-free survival. Results of multivariable analysis showed that preoperative neutrophil-to-lymphocyte ratio and the change of neutrophil-to-lymphocyte ratio correlated with cancer relapse remarkably. High preoperative neutrophil-to-lymphocyte ratio and elevated postoperative neutrophil-to-lymphocyte ratio are associated with significant increase in risk of local recurrence as well as distant metastasis. The combination of neutrophil-to-lymphocyte ratio with the other prognostic indicators can be applied in the evaluation of relapse risk in patients with clear cell renal cell carcinoma after radiofrequency ablation.

Real world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States.

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Mato, Anthony R; Thompson, Meghan; Allan, John N; Brander, Danielle M; Pagel, John M; Ujjani, Chaitra S; Hill, Brian T; Lamanna, Nicole; Lansigan, Frederick; Jacobs, Ryan; Shadman, Mazyar; Skarbnik, Alan P; Pu, Jeffrey J; Barr, Paul M; Sehgal, Alison R; Cheson, Bruce D; Zent, Clive S; Tuncer, Hande H; Schuster, Stephen J; Pickens, Peter V; Shah, Nirav N; Goy, Andre; Winter, Allison M; Garcia, Christine; Kennard, Kaitlin; Isaac, Krista; Dorsey, Colleen; Gashonia, Lisa M; Singavi, Arun K; Roeker, Lindsey E; Zelenetz, Andrew; Williams, Annalynn; Howlett, Christina; Weissbrot, Hanna; Ali, Naveed; Khajavian, Sirin; Sitlinger, Andrea; Tranchito, Eve; Rhodes, Joanna; Felsenfeld, Joshua; Bailey, Neil; Patel, Bhavisha; Burns, Timothy F; Yacur, Melissa; Malhotra, Mansi; Svoboda, Jakub; Furman, Richard R; Nabhan, Chadi

2018-06-07

Venetoclax is a BCL2 inhibitor approved for 17p-deleted relapsed/refractory chronic lymphocytic leukemia with activity following kinase inhibitors. We conducted a multicenter retrospective cohort analysis of patients with CLL treated with venetoclax to describe outcomes, toxicities, and treatment selection following venetoclax discontinuation. A total of 141 chronic lymphocytic leukemia patients were included (98% relapsed/refractory). Median age at venetoclax initiation was 67 years (range 37-91), median prior therapies was 3 (0-11), 81% unmutated IGHV, 45% del(17p), and 26.8% complex karyotype (≥ 3 abnormalities). Prior to venetoclax initiation, 89% received a B-cell receptor antagonist. For tumor lysis syndrome prophylaxis, 93% received allopurinol, 92% normal saline, and 45% rasburicase. Dose escalation to the maximum recommended dose of 400 mg daily was achieved in 85% of patients. Adverse events of interest included neutropenia in 47.4%, thrombocytopenia in 36%, tumor lysis syndrome in 13.4%, neutropenic fever in 11.6%, and diarrhea in 7.3%. The overall response rate to venetoclax was 72% (19.4% complete remission). With a median follow up of 7 months, median progression free survival and overall survival for the entire cohort have not been reached. To date, 41 venetoclax treated patients have discontinued therapy and 24 have received a subsequent therapy, most commonly ibrutinib. In the largest clinical experience of venetoclax-treated chronic lymphocytic leukemia patients , the majority successfully completed and maintained a maximum recommended dose. Response rates and duration of response appear comparable to clinical trial data. Venetoclax was active in patients with mutations known to confer ibrutinib resistance. Optimal sequencing of newer chronic lymphocytic leukemia therapies requires further study. Copyright © 2018, Ferrata Storti Foundation.

Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients

NARCIS (Netherlands)

Hoekstra, PJ; Bijzet, J; Limburg, PC; Steenhuis, MP; Troost, PW; Oosterhoff, MD; Korf, J; Kallenberg, CGM; Minderaa, RB

Objective: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/ 17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of

Morphologic identification of atypical chronic lymphocytic leukemia by digital microscopy.

Science.gov (United States)

Marionneaux, S; Maslak, P; Keohane, E M

2014-08-01

Atypical chronic lymphocytic leukemia (aCLL) is a morphologic variant found in approximately 25% of patients with chronic lymphocytic leukemia (CLL). Although aCLL has a more aggressive course compared to typical CLL (tCLL), it is not usually reported. This retrospective study used digital microscopy to morphologically classify CLL patients as aCLL or tCLL, and determined the prevalence of prognostic markers in each group. CellaVision AB (Lund, Sweden) was used to evaluate lymphocyte morphology on archived blood films of 97 CLL patients, and results of their prognostic marker analysis at diagnosis were obtained. The unpaired t-test, Chi-square, or Fisher's Exact test were used for statistical analysis. 27% of CLL cases were morphologically classified as aCLL. The aCLL group had a higher prevalence of trisomy 12, unmutated IgVH, and CD38 expression (markers associated with poor prognosis), and a lower prevalence of 13q14 deletions compared to tCLL; this was statistically significant. Using digital imaging to identify aCLL is feasible, economical, and may provide clinically relevant prognostic information at diagnosis and during periodic monitoring. Further study of a larger number of patients is needed to assess the clinical utility of reporting aCLL morphology. © 2013 John Wiley & Sons Ltd.

B and T lymphocytes in man. I. Effect of infant thymic irradiation on the circulating B and T lymphocytes

International Nuclear Information System (INIS)

Reddy, M.M.; Goh, K.; Hempelmann, L.H.

1976-01-01

B and T lymphocytes were studied in a group of adults whose thymic glands were irradiated in infancy for alleged thymic enlargement. Two independent methods were used to determine the B and T lymphocytes from each peripheral blood specimen: (1) the relative proportion of cells with surface immunoglobulins (B lymphocytes) and cells forming rosettes with sheep erythrocytes (T lymphocytes); and (2) the relative mitogenic response to phytohemagglutinin (T lymphocytes) and to pokeweed mitogen (B lymphocytes). All specimens were coded. The results obtained indicate: (1) a reduction of B and T lymphocytes; and (2) a decreased mitogenic response of lymphocytes to phytohemagglutinin and pokeweed mitogen in this group of patients as compared with the controls. These observations suggest that (1) the effect of irradiation to the thymus gland on lymphocytes is long lasting and (2) both B and T lymphocytes are affected by irradiation to the thymus gland

Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung cancer patients

International Nuclear Information System (INIS)

Nakayama, Yasuhiro; Makino, Shigeki; Fukuda, Yasuki; Min, Kyong-Yob; Ikemoto, Toshiyuki; Shimizu, Akira; Ohsawa, Nakaaki

1995-01-01

To investigate the influence of thoracic irradiation on immunological competence in patients with lung cancer, we examined the changes in peripheral blood lymphocyte subsets in 15 patients before and after radiation therapy by two-color flow cytometry techniques. After radiation therapy, the percentage and the absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+and/orCD16+ cells (NK cells) decreased. The percentage of CD4+ human leukocyte antigen-DR(HLA-DR)+ cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells) increased, although the absolute number did not change significantly. Naive T cells may be more selectively damaged than memory T cells by thoracic irradiation, through their recirculation behavior. The reduction of natural killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of HLA-DR positive T lymphocytes was significantly increased, and thus the possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore, thoracic irradiation has numerous varied effects on the immunological system of lung cancer patients. (author)

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

Energy Technology Data Exchange (ETDEWEB)

Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Partner Site Munich, Munich (Germany); Geinitz, Hans [Johannes Kepler University, Department of Radiation Oncology, Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern and Medical Faculty, Linz (Austria); Duma, Marciana N. [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany)

2017-08-15

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3{sup +} T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [German] Die Strahlentherapie (RT) ist eine bewaehrte Behandlung beim primaeren und rezidivierten Prostatakarzinoms. In dieser Studie wurde der Einfluss einer definitiven und Salvage RT auf die Zusammensetzung der Lymphozytensubpopulationen verglichen, um potenzielle Immuneffekte einer RT zu analysieren. In die Studie wurden 33 Prostatakarzinompatienten eingeschlossen

Can Serum Neutrophil-to-Lymphocyte Ratio Be a Predictive Biomarker to Help Differentiate Active Chronic Otitis Media From Inactive Chronic Otitis Media?

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Tansuker, Hasan Deniz; Eroğlu, Sinan; Yenigün, Alper; Taşkin, Ümit; Oktay, Mehmet Faruk

2017-05-01

The authors' aim was to investigate whether serum neutrophil to lymphocyte ratio might be used as a predictive biomarker to help differentiate active from inactive chronic otitis media (COM). Two hundred fifty-nine patients having inactive COM received tympanoplasty without mastoidectomy and were identified as Group 1. On the other hand, 254 patients having active COM received tympanoplasty with mastoidectomy and were identified as Group 2. Routine hemogram tests were performed preoperatively for both the groups. By performing a chart review, white blood cell count, red blood cell count, hemoglobin, hematocrit, platelet, and mean platelet volume values were compared between the groups in an age-matched and sex-matched manner. A total of 513 COM patients with age range of 7 to 65 years were included in the study. Two hundred seventy-five patients (53.6%) were male, 238 were (46.4%) female. Preoperatively both serum neutrophil and lymphocyte counts were significantly higher in Group 2 (P = 0.015 and P = 0.004, respectively). However, the neutrophil-to-lymphocyte ratios between the groups were not significantly different (P = 0.511). No statistically significant differences were identified from preoperative neutrophil-to-lymphocyte ratios between patients having active COM and inactive COM. Level NA.

Correlation between the neutrophil-lymphocyte count ratio and bacterial infection in patient with human immunodeficiency virus

Science.gov (United States)

Kusnadi, D.; Liwang, M. N. I.; Katu, S.; Mubin, A. H.; Halim, R.

2018-03-01

Parameters for starting antibiotic therapy such as CRP andleukocytosis are considered non-specific. Previous studies have shown the Neutrophil-Lymphocyte Count Ratio (NLCR) can serve as the basis of bacterial infection, the level of infection, and the basis of antibiotic therapy. Compared with the Procalcitonin parameter, this NLCR is rapid, an inexpensive and requires no additional sampling. To determine the correlation between The Neutrophil-LymphocyteCount Ratio to bacterial infection in HIV patients. This study was a cross-sectional observational approach to HIV subject at Wahidin Sudirohusodo and Hasanuddin University Hospital. The subjects performed routine blood, microbiology test,and blood Procalcitonin levels tests. Then performed NLCR calculations based on routine blood results. The subjects then grouped the presence or absence of bacterial infection.In 146 study subjects, there were 78 (53.4%) with bacterial infections and 68 (46.6%) without bacterial infection as controls. Subjects with bacterial infections had higher total neutrophils (84.83) compared with non-bacterial infections. Subjects with bacterial infections had total lymphocytes with an average of 8.51 lower than non-bacterial infections. Subjects with bacterial infections had higher NLCR values with an average of 12.80. The Neutrophil-Lymphocyte Count Ratio can become a marker of bacterial infection in HIV patients.

Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells.

Science.gov (United States)

Kanakry, Christopher G; Hess, Allan D; Gocke, Christopher D; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B Douglas; Levitsky, Hyam; Karp, Judith E

2011-01-13

Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4(+) and included a greatly expanded population of CD3(+)CD4(+)CD25(+)Foxp3(+) T cells. Recovering CD3(+)CD4(+)CD25(+)Foxp3(+) T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML.

Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study.

Science.gov (United States)

O'Brien, Susan; Jones, Jeffrey A; Coutre, Steven E; Mato, Anthony R; Hillmen, Peter; Tam, Constantine; Österborg, Anders; Siddiqi, Tanya; Thirman, Michael J; Furman, Richard R; Ilhan, Osman; Keating, Michael J; Call, Timothy G; Brown, Jennifer R; Stevens-Brogan, Michelle; Li, Yunfeng; Clow, Fong; James, Danelle F; Chu, Alvina D; Hallek, Michael; Stilgenbauer, Stephan

2016-10-01

The TP53 gene, encoding tumour suppressor protein p53, is located on the short arm of chromosome 17 (17p). Patients with 17p deletion (del17p) chronic lymphocytic leukaemia have poor responses and survival after chemoimmunotherapy. We assessed the activity and safety of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, in relapsed or refractory patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma. We did a multicentre, international, open-label, single-arm study at 40 sites in the USA, Canada, Europe, Australia, and New Zealand. Patients (age ≥18 years) with previously treated del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was overall response in the all-treated population per International Workshop on Chronic Lymphocytic Leukaemia 2008 response criteria modified for treatment-related lymphocytosis. Preplanned exploratory analyses were progression-free survival, overall survival, sustained haematological improvement, and immunological improvement. Patient enrolment is complete, but follow-up is ongoing. Treatment discontinuation owing to adverse events, unacceptable toxicity, or death were collected as a single combined category. This study is registered with ClinicalTrials.gov, number NCT01744691. Between Jan 29, 2013, and June 19, 2013, 145 patients were enrolled. The all-treated population consisted of 144 patients with del17p chronic lymphocytic leukaemia or small lymphocytic lymphoma who received at least one dose of study drug, with a median age of 64 years (IQR 57-72) and a median of two previous treatments (IQR 1-3). At the prespecified primary analysis after a median follow-up of 11·5 months (IQR 11·1-13·8), 92 (64%, 95% CI 56-71) of 144 patients had an overall response according to independent review committee assessment; 119 patients (83%, 95% CI 76-88) had an overall

[Lymphocyte transformation test following stimulation with a protein factor from neutrophilic granulocytes (PMNL) in psoriasis patients].

Science.gov (United States)

Ruszczak, Z; Ciborska, L; Kaszuba, A

1988-12-01

The lymphocyte transformation test (LTT) was given to 20 healthy subjects and 43 patients with generalized psoriasis vulgaris: it was given right after stimulation with PHA (spontaneous) and after stimulation with allogenic and autogenic protein factor (NPF). NPF was isolated from secondary lysosome granules of peripheral blood neutrophils. The results were analyzed using computer statistic tests. No distinct differences were noticed between the spontaneous transformation test in psoriatic patients compared to the controls. After stimulation with PHA, the percentage of blast cells was significantly lower in patients with psoriasis. When allogenic and autogenic NPF was used for stimulation, the LTT values were significantly higher in the psoriasis group than in the control subjects. This fact points out the increase in sensitivity of lymphocytes to NPF in active psoriasis and the possibility of abnormal neutrophil-lymphocyte interactions in vivo. This phenomenon may be intensified when under the influence of bacterial or viral agents, or medicaments; the degranulation of secondary lysosome granules of neutrophils occurs, causing the release of NPF. These investigations support our opinion that psoriasis is a systemic disease and that NPF plays a considerable role in the psoriatic reaction.

Cytogenetic damage in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients undergoing radiotherapy

International Nuclear Information System (INIS)

Minicucci, E.M.; Ribeiro, L.R.; Camargo, J.L.V. de; Salvadori, D.M.F.

2005-01-01

This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells (MNC) in peripheral blood and buccal mucosa of head-and-neck cancer patients undergoing radiotherapy. MNC frequencies were assessed in 31 patients before, during, and after radiotherapy, and in 17 healthy controls matched for gender, age, and smoking habits. Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells. During treatment, increased MNC frequencies were observed in both cell types. Micronucleated lymphocyte levels remained high in samples collected 30 to 140 days after the end of treatment, while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values. There is controversy over the effects of age, smoking habit, tumor stage, and/or metastasis on MNC frequency. However, increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors >4 cm. In conclusion, the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head-and-neck cancer patients, and that the baseline MNC frequency in these two tissues is not a sensitive marker for head-and neck neoplasm. (author)

Sister chromatid exchanges in X-ray irradiated blood lymphocytes from patients with hereditary diseases with radioresistant DNA synthesis

International Nuclear Information System (INIS)

Pleskach, N.M.; Andriadze, M.I.; Mikhel'son, V.M.; Zhestyanikov, V.D.

1988-01-01

X-ray irradiation induced sister chromatid exchanges (SCE) in blood lymphocytes from patient with Down's syndrome and adult progeria (in both the cases radioresistant DNA synthesis takes place). In normal lymphocytes (in which ionizing radiation inhibits the replicative synthesis of DNA) the rate of SCE rises with the rise of radiation dose. Thus, the rate of SCE in X-ray irradiated lymphocytes is in reverse dependence with radioresistance of replicative synthesis of DNA. The data obtained are explained in accordance with the replicative hypothesis of the SCE nature (Painter, 1980a): in cells of patients with Down's syndrome, xeroderma pigmentosum from 2 and progeria of adults the time of existence of partly replicated clusters of replicons is decreased due to radioresistant replicative synthesis of DNA, but the presence of partly replicated clusters of replicons in necessary for SCE formation. Therefore the rate of SCF in X-irradiated cells of these patients decreases

Peripheral Blood Lymphocyte Depletion After Hepatic Arterial {sup 90}Yttrium Microsphere Therapy for Hepatocellular Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Carr, Brian I., E-mail: brianicarr@hotmail.com [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy); Metes, Diana M. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy)

2012-03-01

Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in addition to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.

Molecular Characterization of Chronic Lymphocytic Leukemia Patients with a High Number of Losses in 13q14

Science.gov (United States)

Rodríguez, Ana Eugenia; Hernández, Jose Ángel; Benito, Rocío; Gutiérrez, Norma C.; García, Juan Luis; Hernández-Sánchez, María; Risueño, Alberto; Sarasquete, M. Eugenia; Fermiñán, Encarna; Fisac, Rosa; de Coca, Alfonso García; Martín-Núñez, Guillermo; de las Heras, Natalia; Recio, Isabel; Gutiérrez, Oliver; De Las Rivas, Javier; González, Marcos; Hernández-Rivas, Jesús M.

2012-01-01

Background Patients with chronic lymphocytic leukemia and 13q deletion as their only FISH abnormality could have a different outcome depending on the number of cells displaying this aberration. Thus, cases with a high number of 13q- cells (13q-H) had both shorter overall survival and time to first therapy. The goal of the study was to analyze the genetic profile of 13q-H patients. Design and Methods: A total of 102 samples were studied, 32 of which served as a validation cohort and five were healthy donors. Results Chronic lymphocytic leukemia patients with higher percentages of 13q- cells (>80%) showed a different level of gene expression as compared to patients with lower percentages (<80%, 13q-L). This deregulation affected genes involved in apoptosis and proliferation (BCR and NFkB signaling), leading to increased proliferation and decreased apoptosis in 13q-H patients. Deregulation of several microRNAs, such as miR-15a, miR-155, miR-29a and miR-223, was also observed in these patients. In addition, our study also suggests that the gene expression pattern of 13q-H cases could be similar to the patients with 11q- or 17p-. Conclusions This study provides new evidence regarding the heterogeneity of 13q deletion in chronic lymphocytic leukemia patients, showing that apoptosis, proliferation as well as miRNA regulation are involved in cases with higher percentages of 13q- cells. PMID:23152777

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Sørensen, Allan Klitgaard; Holmgaard, Dennis Back; Mygind, Lone Hagens

2015-01-01

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive decline in pulmonary function. Neutrophil-to-lymphocyte ratio (NLR), YKL-40 and calprotectin are biomarkers of inflammation and predict mortality in patients with different inflammatory...... diseases. We aimed to investigate the correlation between levels of these three biomarkers and neutrophil granulocyte and lymphocyte count in patients with moderate to very severe COPD stratified by use of systemic glucocorticoids. Furthermore, we studied the ability of these biomarkers to predict all......- and multivariate Cox regression analyses with hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Plasma calprotectin was positively correlated with neutrophil granulocyte count and NLR. No significant association was found between plasma YKL-40 and the cellular biomarkers, irrespective...

Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

Science.gov (United States)

Silveira-Lemos, Denise; Fernandes Costa-Silva, Matheus; Cardoso de Oliveira Silveira, Amanda; Azevedo Batista, Mauricio; Alves Oliveira-Fraga, Lúcia; Soares Silveira, Alda Maria; Barbosa Alvarez, Maria Carolina; Martins-Filho, Olindo Assis; Gazzinelli, Giovanni; Corrêa-Oliveira, Rodrigo; Teixeira-Carvalho, Andréa

2013-01-01

Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group) before and after praziquantel treatment (ACT-TR group). Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI) or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA), increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis. PMID:23401741

Cytokine Pattern of T Lymphocytes in Acute Schistosomiasis mansoni Patients following Treated Praziquantel Therapy

Directory of Open Access Journals (Sweden)

Denise Silveira-Lemos

2013-01-01

Full Text Available Acute schistosomiasis is associated with a primary exposure and is more commonly seen in nonimmune individuals traveling through endemic regions. In this study, we have focused on the cytokine profile of T lymphocytes evaluated in circulating leukocytes of acute Schistosomiasis mansoni-infected patients (ACT group before and after praziquantel treatment (ACT-TR group. Our data demonstrated increased values of total leukocytes, eosinophils, and monocytes in both groups. Interestingly, we have observed that patients treated with praziquantel showed increased values of lymphocytes as compared with noninfected group (NI or ACT groups. Furthermore, a decrease of neutrophils in ACT-TR was observed when compared to ACT group. Analyses of short-term in vitro whole blood stimulation demonstrated that, regardless of the presence of soluble Schistosoma mansoni eggs antigen (SEA, increased synthesis of IFN-γ and IL-4 by T-cells was observed in the ACT group. Analyses of cytokine profile in CD8 T cells demonstrated higher percentage of IFN-γ and IL-4 cells in both ACT and ACT-TR groups apart from increased percentage of IL-10 cells only in the ACT group. This study is the first one to point out the relevance of CD8 T lymphocytes in the immune response induced during the acute phase of schistosomiasis.

Persistence of unstable and stable chromosome aberrations in lymphocytes of cancer patients treated with radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Di Giorgio, M.; Vallerga, M.B.; Taja, M.R. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina); Sardi, M. [Hospital Italiano - Mevaterapia, Buenos Aires (Argentina)

2006-07-01

Background: Radiation-induced DNA damage in human lymphocytes has equal probability of producing both stable or unstable chromosome aberrations (C.A.). Reports of its in vivo persistence show considerable variations. The quantification of unstable C.A. (dicentrics) in peripheral blood lymphocytes (P.B.L.) is the most reliable biological method for estimating whole-body doses of recent overexposures to ionizing radiation. Given that during the division of T cell precursors, proliferative death of cells containing dicentrics reduces the number of such lymphocytes in peripheral blood, dicentric methodology should be modified to account for past exposures. Micronuclei (M.N.) in cytokinesis-blocked human P.B.L. are well established bio markers for assessing radiation damage in vivo. However, persistence of radiation induced M.N. is limited. Unlike dicentrics and M.N., stable C.A. (translocations) identified at present by the FISH technique, seem to be an adequate indicator for the dosimetric evaluation of past exposures, since translocations are not selected against during mitotic division in the haematopoietic stem cells compartment. Nevertheless, for partial -body exposures with high dose there is some evidence that the decline with time of dicentrics causes some reduction in the yield of translocations. Purpose: To assess the persistence along time of dicentrics, M.N. and translocations in lymphocytes of cancer patients after radiotherapy in order to model changes in C.A. frequencies with partial-body exposures. Materials and methods: 22 cancer patients with different tumor sites, treated with radiotherapy, were evaluated through dicentric chromosome, M.N. and FISH techniques with a follow-up time of up to 90 months after the end of radiotherapy. Regression analysis were performed: 1) for dicentric and for M.N. frequencies in relation to time after the end of radiotherapy and total tumor dose; 2) for the percentage of uns table cells in relation to time after the end

Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes

International Nuclear Information System (INIS)

Prusek, W.; Astaldi, G.

1979-01-01

The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than the viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so-called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity. (author)

Effect of in vitro x-irradiation on human peripheral blood T and B lymphocytes

Energy Technology Data Exchange (ETDEWEB)

Prusek, W. (Szpital Wojewodzki, Wroclaw (Poland)); Astaldi, G. (The Blood Research Foundation Centre, Tortona (Italy))

1979-01-01

The effect of in vitro irradiation with increasing in logarythmic progress X-ray doses on lymphocyte viability and on T and B lymphocyte populations was studied in normal adults, patients with myasthenia gravis and in patients undergoing long-term steroid therapy. Decrease in numbers of lymphocytes carrying T or B lymphocyte surface markers was higher than the viable cell loss. The decrease showed no linear correlation with X-ray doses applied, which might reflect the existence of radioresistant T and B lymphocytes. A higher so-called early radiosensitivity of B lymphocytes was demonstrated. In patients with myasthenia gravis early radioresistance of T lymphocytes was detected. In patients undergoing long-term steroid therapy, an increase in numbers of cells lacking markers of any of lymphocyte populations was found in parallel with a decrease in T lymphocyte number which, in these patients, showed a higher radiosensitivity.

Chronic lymphocytic leukemia/small lymphocytic lymphoma presenting as septic arthritis of the shoulder

Energy Technology Data Exchange (ETDEWEB)

Donovan, Andrea; Schweitzer, Mark E.; Nomikos, George [NYU Hospital for Joint Diseases, New York, NY (United States); Garcia, Roberto A. [Bellevue Hospital Center, New York, NY (United States)

2008-11-15

We report a case of a 53-year-old man presenting with shoulder pain mimicking septic arthritis. Laboratory findings were atypical. Biopsy performed to assess for possible osteomyelitis demonstrated chronic lymphocytic leukemia/small lymphocytic lymphoma. Intra-articular lymphoma is a rare but important consideration in patients with atypical clinical presentation. Imaging alone may be insufficient to render diagnosis as lymphoma can mimic infection, synovial hypertrophic processes, and depositional arthropathy. (orig.)

Relationship between Neutrophil-to-Lymphocyte Ratio and Prognosis in Patients with Deep Neck Space Infection

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Engin Şengül

2016-03-01

Full Text Available Objective: The aim of this study was to demonstrate if there is any relation between the neutrophil-to-lym­phocyte ratio and prognosis in patients with deep neck space infections Methods: One hundred eight patients who were interned and treated due to deep neck infection in department of otolaryngology between January 2010 and January 2015 were analyzed. Demographics, clini­cal data, complications and treatment results of patients were evaluated. Pediatric patients between the age of 0 and 14, the patients who had only peritonsillary abscess, infection secondary to trauma were excluded from study. During follow-up and treatment duration the patients with deep neck infections were divided into two groups ac­cording to whether they had any complication (group 1 or not (group 2. Results: Fourteen (13% patients with deep neck in­fections had life-threatening complications whereas 94 (87% did not have any complication during follow-up and treatment duration. The mean neutrophil-to-lymphocyte ratio in patients with complications was significantly high­er than the patients without any complications (p0.05. Conclusion: This study showed that the neutrophil-to-lymphocyte ratio can be used as a cheap, easily obtained and predictive prognostic factor in patients with deep neck infections.

Diffuse large B-cell lymphoma (Richter syndrome) in patients with chronic lymphocytic leukaemia (CLL): a cohort study of newly diagnosed patients.

Science.gov (United States)

Parikh, Sameer A; Rabe, Kari G; Call, Timothy G; Zent, Clive S; Habermann, Thomas M; Ding, Wei; Leis, Jose F; Schwager, Susan M; Hanson, Curtis A; Macon, William R; Kay, Neil E; Slager, Susan L; Shanafelt, Tait D

2013-09-01

Nearly all information about patients with chronic lymphocytic leukaemia (CLL) who develop diffuse large B-cell lymphoma [Richter syndrome (RS)] is derived from retrospective case series or patients treated on clinical trials. We used the Mayo Clinic CLL Database to identify patients with newly diagnosed CLL between January 2000 and July 2011. Individuals who developed biopsy-proven RS during follow-up were identified. After a median follow-up of 4 years, 37/1641 (2·3%) CLL patients developed RS. The rate of RS was approximately 0·5%/year. Risk of RS was associated with advanced Rai stage at diagnosis (P CLL (1%/year). Stereotyped B-cell receptors (odds-ratio = 4·2; P = 0·01) but not IGHV4-39 family usage was associated with increased risk of RS. Treatment with combination of purine analogues and alkylating agents increased the risk of RS three-fold (odds-ratio = 3·26, P = 0·0003). Median survival after RS diagnosis was 2·1 years. The RS prognosis score stratified patients into three risk groups with median survivals of 0·5 years, 2·1 years and not reached. Both underlying characteristics of the CLL clone and subsequent CLL therapy influence the risk of RS. Survival after RS remains poor and new therapies are needed. © 2013 John Wiley & Sons Ltd.

Chronic lymphocytic leukemia: concepts and observations

Energy Technology Data Exchange (ETDEWEB)

Chandra, P.; Chanana, A.D.; Chikkappa, G.; Cronkite, E.P.

1977-01-01

Thirty-five patients with chronic lymphocytic leukemia (CLL) were studied for assessment of total body leukemic mass and abnormality in T-lymphocyte function associated with clinical stages of CLL. Total body potassium (TBK), an indicator of lean body mass, was found to correlate well with increase in the clinical stage of the disease. Use of TBK for monitoring the regression and relapse of leukemic load is suggested. No correlation was found between whole cell and nuclear volumes of lymphocytes in CLL patients and clinical stages of the disease. Blast transformation and proliferation under phytohemagglutinin (PHA) stimulation appeared to be normal in purified T cells of early stages and abnormal in the late stages of disease.

B Lymphocytes in Rheumatoid Arthritis and the Effects of Anti-TNF-α Agents on B Lymphocytes: A Review of the Literature.

Science.gov (United States)

Pala, Ozlem; Diaz, Alain; Blomberg, Bonnie B; Frasca, Daniela

2018-05-22

The aim of this article was to review published research related to B lymphocytes in rheumatoid arthritis, their role in the pathogenesis of the disease, the effects of tumor necrosis factor (TNF)-α inhibitors on B lymphocytes, the risk for infection, and responses to vaccines. A PubMed search was conducted to review recent advances related to B lymphocytes and the effects of anti-TNF-α on B lymphocytes in rheumatoid arthritis. B lymphocytes play an important role in the pathogenesis of rheumatoid arthritis. In this review, we summarize the major mechanisms by which B lymphocytes play a pathologic role in the development and propagation of the disease, as B lymphocytes are recruited to the synovial fluid, where they contribute to local inflammation through the secretion of pro-inflammatory mediators (cytokines, chemokines, micro-RNAs) and present antigens to T cells. We discuss the effects of TNF-α, either direct or indirect, on B lymphocytes expressing receptors for this cytokine. We also show that total B-cell numbers have been reported to be reduced in the blood of patients with rheumatoid arthritis versus healthy controls, but are significantly increased up to normal levels in patients undergoing anti-TNF-α therapy. As for B-cell subsets, controversial results have been reported, with studies showing decreased frequencies of total memory B cells (and memory subsets) and others showing no differences in patients versus healthy controls. Studies investigating the effects of anti-TNF-α therapy have also given controversial results, with therapy found to increase (or not) the frequency of memory B lymphocytes, in patients with rheumatoid arthritis versus healthy controls. Those highly variable results could have been due to differences in patient characteristics and limited numbers of subjects. Finally, we summarize the effects of blocking TNF-α with anti-TNF-α agents on possible infections that patients with rheumatoid arthritis may contract, as well as on

Predictors of change in CD4 lymphocyte count and weight among HIV infected patients on anti-retroviral treatment in Ethiopia: a retrospective longitudinal study.

Directory of Open Access Journals (Sweden)

Ayalu A Reda

Full Text Available Antiretroviral treatment (ART has been introduced in Ethiopia a decade ago and continues to be scaled up. However, there is dearth of literature on the impact of ART on changes in CD4 lymphocyte count and weight among patients on treatment.To determine the predictors of change in CD4 lymphocyte count and weight among HIV/AIDS infected patients taking antiretroviral treatment in eastern Ethiopia.A retrospective cohort study was conducted among HIV/AIDS patients taking ART from 2005 to 2010. A sample of 1540 HIV infected adult patients who started antiretroviral therapy in hospitals located in eastern Ethiopia were included in the study. The primary outcomes of interest were changes in CD4 count and weight. Descriptive statistics and multivariable regression analyses were performed to examine the outcomes among the cohort.Both the median CD4 lymphocyte counts and weight showed improvements in the follow up periods. The multivariate analysis shows that the duration of ART was an important predictor of improvements in CD4 lymphocyte count (beta 7.91; 95% CI 7.48-8.34; p 0.000 and weight (beta 0.15; 95% CI 0.13-0.18; p 0.000. Advanced WHO clinical stage, lower baseline CD4 cell count, and baseline hemoglobin levels were factors associated with decline in weight. Actively working patients had higher CD4 lymphocyte count and weight compared to those that were ambulatory (p<0.05.We detected a substantial increment in weight and CD4 lymphocyte count among the patients who were taking ART in eastern Ethiopia. Patients who are of older age, with low initial CD4 lymphocyte count, late stage of the WHO clinical stages and lower hemoglobin level may need special attention. The reasons for the improved findings on CD4 count and weight throughout the five years of follow up merit further investigation.

Economic evaluation of therapeutic sequences in the treatment of patients with chronic lymphocytic leukemia and coexisting conditions

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Antonio Cuneo

2017-10-01

Full Text Available Economic evaluation of therapeutic sequences in the treatment of patients with chronic lymphocytic leukemia and coexisting conditionsIntroductionChronic lymphocytic leukemia (CLL is a chronic lymphoproliferative syndrome and it is the most common hematological malignancy in Western countries. It has a tendency to develop subsequent relapses, so affected patients are likely to undergo more than one line of treatment.MethodsRather than evaluating the cost-effectiveness of individual therapeutic agents, it becomes therefore recommendable for decision-makers to identify an optimal sequencing of such agents. A four-year cost-consequence analysis was conducted, comparing three alternative strategies for the first-line treatment of patients with previously untreated CLL and coexisting conditions: i obinutuzumab with chlorambucil (Obi-Clb, ii rituximab with chlorambucil (Rtx-Clb, and iii ofatumumab with chlorambucil (Ofa-Clb. Only drug costs were considered in the analysis.ResultsIn two trials, median time to next treatment (TTNT was longer in Obi-Clb (51.1 months as compared to Rtx-Clb (38.2 months or to Ofa-Clb (39.8 months. Therefore, during a 48-month time horizon, patients treated with Obi-Clb would maintain on average the first line treatment; on the contrary, patients treated with Rtx-Clb or with Ofa-Clb would receive on average a second line treatment consisting in the majority of cases of ibrutinib monotherapy, or rituximab with idelalisib or rituximab with bendamustine. The sequence using Obi-Clb regimen in first line showed the lower mean cost of treatment: €22,958 over the 48-month time horizon. Sensitivity analyses on a couple of scenarios provided similar conclusions in terms of overall costs.ConclusionObi-Clb as first-line treatment appears a recommendable strategy in terms of drug costs in the treatment of patients with previously untreated CLL and coexisting conditions.

Benfotiamine reduces genomic damage in peripheral lymphocytes of hemodialysis patients.

Science.gov (United States)

Schupp, Nicole; Dette, Eva Maria; Schmid, Ursula; Bahner, Udo; Winkler, Michaela; Heidland, August; Stopper, Helga

2008-09-01

Hemodialysis patients have an elevated genomic damage in peripheral blood lymphocytes (PBLs) and an increased cancer incidence, possibly due to accumulation of uremic toxins like advanced glycation end products (AGEs). Because the vitamin B1 prodrug benfotiamine reduces AGE levels in experimental diabetes, and dialysis patients often suffer from vitamin B1 deficiency, we conducted two consecutive studies supplementing hemodialysis patients with benfotiamine. In both studies, genomic damage was measured as micronucleus frequency of PBLs before and at three time-points after initiation of benfotiamine supplementation. AGE-associated fluorescence in plasma, and in the second study additionally, the antioxidative capacity of plasma was analyzed. Benfotiamine significantly lowered the genomic damage of PBLs in hemodialysis patients of both studies independent of changes in plasma AGE levels. The second study gave a hint to the mechanism, as the antioxidative capacity of the plasma of the treated patients clearly increased, which might ameliorate the DNA damage.

Decrease of CD4+ T lymphocytes in patients with H1N1 in early stage and its clinical significances

International Nuclear Information System (INIS)

Zuo Lingyun; Zhao Wei; Zhao Hong; Yu Haiying; Sun Weiwei

2010-01-01

Objective: To observe the change of CD4 + T Lymphocytes in patients with H1N1 at early stage and figure out its clinical significances on the progress and therapeutic selection of H1N1. Methods: The absolute counts of T lymphocyte subset from the peripheral blood samples of 48 H1N1 patients in first ten days' duration were detected by flow cytometry, and the serial chest CT examinations were performed. Results: In all 48 clinical cases, 28 cases were in normal range of CD4 + lymphocyte absolute count, whose pulmonary lesions were limited and illness condition stayed in the stability, they didn't need steroid. In the other 20 cases with low level of CD4 + , 4 cases' illness presented the progressive development and needed to be treated with steroid and 16 cases with lightly decreased CD4 + level which had a stable condition without treatment with steroid. The result of Pearson correlation analysis showed that there were negative correlations between absolute count of CD4 + cells and pulmonary lesions (r=-0.299, P + cell absolute count of H1N1 patients at early stage indicates the worse condition of pulmonary lesions. The patients with remarkable decrease of CD4 + lymphocytes are in need of treatment with steroid. (authors)

Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease.

Science.gov (United States)

Vitales-Noyola, Marlen; Martínez-Martínez, Rita; Loyola-Rodríguez, Juan P; Baranda, Lourdes; Niño-Moreno, Perla; González-Amaro, Roberto

2017-08-01

Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69 + Treg lymphocytes in patients with chronic periodontal disease. Peripheral blood samples (n = 33) and gingival tissue (n = 9) were obtained from patients with chronic periodontal disease. Blood samples from 25 healthy individuals were also studied. Levels of CD69 + Treg lymphocytes in peripheral blood and gingival tissue were determined by six-color multiparametric flow cytometry, immunofluorescence, and immunohistochemistry. The immune regulatory function of CD69 + Treg cells was tested by an in vitro assay of inhibition of lymphocyte activation. Percentages of CD69 + Treg cells were significantly higher in the peripheral blood from patients with active periodontal disease compared to healthy controls, and these percentages inversely correlated with the periodontal attachment loss. Increased numbers of these Treg cells were detected in the gingival tissue from active PD patients compared to their peripheral blood. However, the suppressive function of CD69 + Treg cells was significantly diminished in patients with periodontal disease compared to healthy controls. Our data suggest that CD69 + Treg cells seem to be another important piece in the complex immunopathogenesis of periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bestatin treatment enhances the recovery of radiation induced impairments of the immunological reactivity of the blood lymphocyte population in bladder cancer patients

International Nuclear Information System (INIS)

Blomgren, H.; Edsmyr, F.; Stedingk, L.V. von; Wasserman, J.

1986-01-01

Bestatin, an immunostimulating substance of microbial origin, was examined for its capacity to augment immune responses of blood lymphocytes in bladder cancer patients having received a full course of local irradiation (64 Gy). Following irradiation the patients became lymphopenic and the lymphocytes exhibited impaired mitogenic responses to phytohemagglutinin (PHA) and purified protein derivative of tuberculin (PPD) and reduced poke weed mitogen induced secretion of immunoglobulins in vitro. Patients who were randomized to receive daily oral Bestatin treatment exhibited enhanced recoveries of PHA- and PPD- responses and enhanced recovery of the IgM secreting capacity compared to irradiated patients who did not receive Bestatin. Repopulation of the blood lymphocyte population, however, was not enhanced by Bestatin treatment. It is concluded that Bestatin treatment may enhance the recovery of radiation induced functional defects of the immune system in cancer patients

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

Science.gov (United States)

Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

2018-03-27

The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Monitoring of DNA and cytogenetic damage in lymphocytes in patients with skin cancer disease

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Dyga, W.; Krasnowolski, S.; Wierzewska, A.; Budzanowska, E.

1999-01-01

One major oncogenesis process is activation of proto-oncogenes by point mutations or chromosomal translocations. There is substantial evidence that indicates that human carcinogenesis involves loss of heterozygosity of certain chromosomes. Our study aimed at searching the possible association between cancer and DNA and cytogenetic abnormalities induced in lymphocytes of people with various categories of skin cancer cells. Fresh blood was collected by venepuncture from 25 individuals (including nine prior to cancer treatment). All patients were nonsmoking males, however 42.3% of them were former smokers. Blood samples were divided into two parts; in the first part of samples cytogenetic studies were performed immediately, while lymphocytes from the other part were isolated and stored at -70 0C for further studies in vitro. A single cell gel electrophoresis assay (SCGE), known as a Comet assay, was performed on them to study individual susceptibility to the induction of DNA damage by UV or radiation and to estimate variability in cellular repair capabilities. On average 220 good metaphase spreads per sample in the first mitotic division, and 100 spreads per sample in the second division were accepted for analysis of the cytogenetic damage. Chromosome and chromatid type aberrations were scored in the cells in the first mitosis, and expressed as total aberration frequency including and excluding gaps. Sister chromatid exchanges , high frequency cells and proliferating rate index were screened and evaluated in the second mitosis. Each patient showed a level exceeding (in at least one of the cytogenetic biomarker) the biomarker level in a reference group. In order to estimate susceptibility of people to environmentally induced damage, the isolated lymphocytes were irradiated with 2 Gy dose of X-rays or 6 J/m 2 of UV radiation, and the single cell gel electrophoresis (SCGE assay) was performed. To compare various individual capabilities to repair the induced damage

Chronic lymphocytic thyroiditis does not influence the risk of recurrence in patients with papillary thyroid carcinoma and excellent response to initial therapy.

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Carvalho, Marina S; Rosario, Pedro W; Mourão, Gabriela F; Calsolari, Maria R

2017-03-01

This study evaluated the recurrence in patients with papillary thyroid cancer and an excellent response to initial therapy, comparing those with and without chronic lymphocytic thyroiditis. This was a prospective study. Patients who met the following criteria were selected: diagnosis of papillary thyroid cancer; submitted to total thyroidectomy followed or not by ablation with 131 I; and neck ultrasonography without abnormalities, nonstimulated thyroglobulina (Tg) ≤0.2 ng/ml, and undetectable antithyroglobulin antibodies (TgAb) 12-18 months after initial therapy. The patients were divided into two groups: group A, with chronic lymphocytic thyroiditis on histology; group B, without chronic lymphocytic thyroiditis on histology. Groups A and B were similar in terms of sex and age of the patients, characteristics of the tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients with chronic lymphocytic thyroiditis were more likely to progress to persistently borderline TgAb. No patient had positive TgAb (above the reference value) during follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but that returned to undetectable spontaneously, and in 1/13 (7.7 %) with persistently borderline TgAb. These rates did not differ significantly (p = 0.25). The results of the present study showed the absence of an association between chronic lymphocytic thyroiditis and recurrence risk at least in patients with an excellent response to initial therapy.

Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging in newly diagnosed MM patients treated upfront with novel agents.

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Romano, A; Parrinello, N L; Consoli, M L; Marchionni, L; Forte, S; Conticello, C; Pompa, A; Corso, A; Milone, G; Di Raimondo, F; Borrello, I

2015-11-01

Recent reports identify the ratio between absolute neutrophil count (ANC) and absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. We retrospectively examined the NLR in a cohort of 309 newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents. NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9 (range 0.4-15.9). Higher NLR was independent of international staging system (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS estimates were, respectively, 18.2 and 36.4 % for patients with NLR ≥ 2 versus 25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years, N = 179), NLR ≥ 2 had a negative prognostic impact on both PFS and OS, in all ISS stages. By combining ISS stage and NLR in a model limited to young patients, we found that 19 % of the patients were classified as very low risk, 70 % standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and 10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and very high-risk groups. We found NLR to be a predictor of PFS and OS in MM patients treated upfront with novel agents. NLR can be combined with ISS staging system to identify patients with dismal outcome. However, larger cohorts and prospective studies are needed to use NLR as additional parameter to personalise MM therapy in the era of novel agents.

Analysis of the numbers of B, T and subpopulation lymphocytes in patients with breast cancer submitted to a different radiotherapy schedules

International Nuclear Information System (INIS)

Andrade, J.M. de.

1989-01-01

The behaviour of T and B lymphocytes subpopulations was evaluated in patients with breast cancer submitted to 3 different schedules of radiotherapy. The assays were carried out before and immediately after the end of treatment. T lymphocytes and the helper/inducer (CD 4 ) and suppressor/cytotoxic (CD 8 ) subpopulations were counted by indirect immunofluorescence with monoclonal antibodies of the OKT series. The number of B lymphocytes was obtained by direct immunofluorescence with fluorescein-conjugated anti-human Ig antibodies. The patients were divided into 3 groups: irradiation of the breast only; irradiation of the lymph-draining areas; irradiation of the breast, of the lymph-draining area and of the sternal area. (author)

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

DEFF Research Database (Denmark)

Langhoff, E; Ladefoged, J; Ødum, Niels

1986-01-01

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD......). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte...... responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte...

Monocyte and lymphocyte surface molecules in severe sepsis and non-septic critically ill Patients.

Science.gov (United States)

Jämsä, Joel; Syrjälä, Hannu; Huotari, Virva; Savolainen, Eeva-Riitta; Ala-Kokko, Tero

2017-06-01

The aim of the present study was to investigate whether expression of monocyte and lymphocyte surface molecules differs between patients with severe sepsis and non-septic patients treated in the intensive care unit (ICU). The expression of monocyte CD14, CD40, CD80 and HLA-DR, and lymphocyte CD69 were analyzed using quantitative flow cytometry on three consecutive days in 27 patients with severe sepsis and in 15 non-septic patients. Receiver operating characteristic analyses were performed and each corresponding area under the curve (AUC) was determined. The results showed that the expression levels of CD40 on monocytes and CD69 on CD4+ T cells and on natural killer (NK) cells were highest in patients with severe sepsis (p sepsis and positive blood culture compared with those with negative blood culture (p sepsis detection were 0.836 for CD40, 0.872 for CD69 on NK cells, and 0.795 for CD69 on CD4+ T cells. These findings suggest that monocyte CD40 and CD69 on NK cells and CD4+ T cells could prove useful for new approaches in the identification of severe sepsis in the ICU. © 2017 APMIS. Published by John Wiley & Sons Ltd.

p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

NARCIS (Netherlands)

Blume, C. J.; Hotz-Wagenblatt, A.; Hüllein, J.; Sellner, L.; Jethwa, A.; Stolz, T.; Slabicki, M.; Lee, K.; Sharathchandra, A.; Benner, A.; Dietrich, S.; Oakes, C. C.; Dreger, P.; te Raa, D.; Kater, A. P.; Jauch, A.; Merkel, O.; Oren, M.; Hielscher, T.; Zenz, T.

2015-01-01

Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We

Lymphocytes From Patients With Type 1 Diabetes Display a Distinct Profile of Chromatin Histone H3 Lysine 9 Dimethylation

Science.gov (United States)

Miao, Feng; Smith, David D.; Zhang, Lingxiao; Min, Andrew; Feng, Wei; Natarajan, Rama

2008-01-01

OBJECTIVE—The complexity of interactions between genes and the environment is a major challenge for type 1 diabetes studies. Nuclear chromatin is the interface between genetics and environment and the principal carrier of epigenetic information. Because histone tail modifications in chromatin are linked to gene transcription, we hypothesized that histone methylation patterns in cells from type 1 diabetic patients can provide novel epigenetic insights into type 1 diabetes and its complications. RESEARCH DESIGN AND METHODS—We used chromatin immunoprecipitation (ChIP) linked to microarray (ChIP-chip) approach to compare genome-wide histone H3 lysine 9 dimethylation (H3K9me2) patterns in blood lymphocytes and monocytes from type 1 diabetic patients versus healthy control subjects. Bioinformatics evaluation of methylated candidates was performed by Ingenuity Pathway Analysis (IPA) tools. RESULTS—A subset of genes in the type 1 diabetic cohort showed significant increase in H3K9me2 in lymphocytes but not in monocytes. CLTA4, a type 1 diabetes susceptibility gene, was one of the candidates displaying increased promoter H3K9me2 in type 1 diabetes. IPA identified two high-scoring networks that encompassed genes showing altered H3K9me2. Many of them were associated with autoimmune and inflammation-related pathways, such as transforming growth factor-β, nuclear factor-κB, p38 mitogen-activated protein kinase, toll-like receptor, and interleukin-6. IPA also revealed biological relationships between these networks and known type 1 diabetes candidate genes. CONCLUSIONS—The concerted and synergistic alteration of histone methylation within the identified network in lymphocytes might have an effect on the etiology of type 1 diabetes and its complications. These studies provide evidence of a novel association between type 1 diabetes and altered histone methylation of key genes that are components of type 1 diabetes–related biological pathways and also a new

Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

International Nuclear Information System (INIS)

Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

1987-01-01

We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases

The clinical investigation of OX40/OX40L from lymphocytes of patients with Graves' disease after 131I therapy

International Nuclear Information System (INIS)

Shi Bimin; Du Xuan; Wang Qin

2013-01-01

Objective To investigate the clinical value and the expression of OX40/OX40L from lymphocytes of patients with Graves' disease (GD) before and after 131 I therapy.Methods The expression of OX40/OX40L on T,B lymphocytes and the percentage of lymphocyte subsets were analyzed using immunofluorescence staining and flow cytometry in 32 patients with GD before and after 131 I therapy.Twenty-five healthy subjects were considered as the control group.The data between GD patients and controls were compared with two-sample t test.The correlation between the expression of OX40/OX40L and the function of thyroid (FT3,FT4 and TRAb level) was performed with linear correlation analysis.Results Compared with the healthy subjects,the percentage of CD4+ T cells and ratio of CD4+/CD8+ were decreased ((34.36 ±6.73)% vs (45.60-±5.72)%,t=2.634; 1.24±0.26 vs 1.84±0.37,t=2.125,both P<0.05).Whereas the percentage of CD19+ B cells in patients with GD were significantly higher than that in healthy subjects ((21.42 ±3.92)% vs (15.35 ± 3.15)%,t =2.653,P<0.05).The expression of OX40 increased in CD4+ T lymphocytes ((12.92 ± 2.26) %) and OX40L expression was up-regulated in CD19+ B lymphocytes ((15.33 ± 3.75)%) of patients with GD,compared with the healthy subjects ((4.19 ±1.45) % and (8.64 ± 1.73) %,respectively,t =2.112 and 2.467,both P<0.05).The expression of OX40 in CD4+ T lymphocytes ((7.65 ± 1.64) %) and OX40L in CD19+ B lymphocytes ((11.50 ±2.72)%) were increased after 131 I therapy(t =2.795,2.393,both P<0.05).The thyroid functions of 32 GD patients were improved.The levels of FT3,FT4 and TRAb decreased significantly after 131 I treatment (from 20.79 ±6.05 to 4.53 ± 2.54,from 49.65 ± 10.12 to 13.69 ± 4.35,and from 24.78 ± 8.46 to 11.74 ±6.19,respectively; t =2.219,2.441 and 2.293,all P<0.05).The levels of FT3 and FT4 were positively correlated with the percentage of OX40 expression in CD4+ T lymphocytes (r =0.65 and 0.73,both P<0.05).TRAb was positively correlated

Expression of the chemokine receptor CXCR4 on lymphocytes of leprosy patients

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V.A. Mendonça

2011-12-01

Full Text Available Leprosy is caused by Mycobacterium leprae, which induces chronic granulomatous infection of the skin and peripheral nerves. The disease ranges from the tuberculoid to the lepromatous forms, depending on the cellular immune response of the host. Chemokines are thought to be involved in the immunopathogenesis of leprosy, but few studies have investigated the expression of chemokine receptors on leukocytes of leprosy patients. In the present study, we evaluated 21 leprosy patients (M/F: 16/5 with a new diagnosis from the Dermatology Outpatient Clinic of the University Hospital, Federal University of Minas Gerais. The control group was composed of 20 healthy members (M/F: 15/5 of the community recruited by means of announcements. The expression of CCR2, CCR3, CCR5, and CXCR4 was investigated by flow cytometry on the surface of peripheral blood lymphocytes. There was a decrease in percentage of CD3+CXCR4+ and CD4+CXCR4+ lymphocytes in the peripheral blood of leprosy patients (median [range], 17.6 [2.7-41.9] and 65.3 [3.9-91.9], respectively compared to the control group (median [range], 43.0 [3.7-61.3] and 77.2 [43.6-93.5], respectively. The percentage of CD4+CXCR4+ was significantly lower in patients with the tuberculoid form (median [range], 45.7 [0.0-83.1] of the disease, but not in lepromatous patients (median [range], 81.5 [44.9-91.9]. The CXCR4 chemokine receptor may play a role in leprosy immunopathogenesis, probably directing cell migration to tissue lesions in tuberculoid leprosy patients.

Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

NARCIS (Netherlands)

Velden, A.M.T. van der

2007-01-01

This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem

Mortality prediction to hospitalized patients with influenza pneumonia: PO2 /FiO2 combined lymphocyte count is the answer.

Science.gov (United States)

Shi, Shu Jing; Li, Hui; Liu, Meng; Liu, Ying Mei; Zhou, Fei; Liu, Bo; Qu, Jiu Xin; Cao, Bin

2017-05-01

Community-acquired pneumonia (CAP) severity scores perform well in predicting mortality of CAP patients, but their applicability in influenza pneumonia is powerless. The aim of our research was to test the efficiency of PO 2 /FiO 2 and CAP severity scores in predicting mortality and intensive care unit (ICU) admission with influenza pneumonia patients. We reviewed all patients with positive influenza virus RNA detection in Beijing Chao-Yang Hospital during the 2009-2014 influenza seasons. Outpatients, inpatients with no pneumonia and incomplete data were excluded. We used receiver operating characteristic curves (ROCs) to verify the accuracy of severity scores or indices as mortality predictors in the study patients. Among 170 hospitalized patients with influenza pneumonia, 30 (17.6%) died. Among those who were classified as low-risk (predicted mortality 0.1%-2.1%) by pneumonia severity index (PSI) or confusion, urea, respiratory rate, blood pressure, age ≥65 year (CURB-65), the actual mortality ranged from 5.9 to 22.1%. Multivariate logistic regression indicated that hypoxia (PO 2 /FiO 2  ≤ 250) and lymphopenia (peripheral blood lymphocyte count pneumonia confirmed a similar pattern and PO 2 /FiO 2 combined lymphocyte count was also the best predictor for predicting ICU admission. In conclusion, we found that PO 2 /FiO 2 combined lymphocyte count is simple and reliable predictor of hospitalized patients with influenza pneumonia in predicting mortality and ICU admission. When PO 2 /FiO 2  ≤ 250 or peripheral blood lymphocyte count pneumonia. © 2015 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.

Studies on the DNA-excision repair in lymphocytes of patients with recurrent Herpes simplex

International Nuclear Information System (INIS)

Fanta, D.; Topaloglou, A.; Altmann, H.

1978-01-01

Investigations of the semiconservatrive DNA replication and the excision repair in lymphocytes of patients with recurrent herpes simplex showed defects that could lead to mutations in the DNA with following lower immuncompetence and possibility for activation of already present oncogenic virus formations within the cellular DNA

Lymphocyte subsets and response to PHA among atomic bomb survivors

International Nuclear Information System (INIS)

Nakao, Susumu; Noguchi, Kyouichi; Eida, Kazuyuki; Tashiro, Kazunori; Hayashida, Ken

1986-01-01

In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

Nebivolol Attenuates Neutrophil Lymphocyte Ratio: A Marker of Subclinical Inflammation in Hypertensive Patients

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Mazhar Hussain

2017-01-01

Full Text Available Background. High value of neutrophil lymphocyte ratio (NLR is a strong independent predictor and biomarker of ongoing vascular inflammation in various cardiovascular disorders. Objective. The main focus of the study is to investigate the effect of nebivolol on NLR in mild to moderate hypertensive patients in comparison with metoprolol. In addition, BMI, blood pressure, TLC count, blood sugar, and lipid profile were also assayed before and after treatment. Materials and Methods. In this 12-week prospective double-blinded randomized study, 120 patients with mild to moderate hypertension were randomly divided into two groups to prescribed daily dose of tab nebivolol 5–10 mg and metoprolol 50–100 mg, respectively, for 12 weeks. The data were analyzed using SPSS 16 software. Results. A total of 100 patients completed the study. Both drugs lowered blood pressure significantly, nebivolol 20.5/10.5 and metoprolol 22.5/11.2 (p<0.001 from baseline. Regarding inflammation, nebivolol reduced total leukocyte count (p=0.005 and neutrophil count (p=0.003 and increased lymphocyte count (p=0.004 as compared to metoprolol. Similarly, nebivolol but not metoprolol significantly reduced NLR ratio (p=0.07. Nebivolol improved lipid profile and blood sugar compared to metoprolol, but values were nonsignificant. Conclusion. Nebivolol has a strong impact on reducing NLR, a marker of subclinical inflammation in hypertensive patients. Moreover NLR can be used as a disease and drug monitoring tool in these patients.

GENOMIC PROFILING BY MULTIPLEX LIGATION - DEPENDENT PROBE AMPLIFICATION IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

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Georgiana-Emilia Grigore

2013-11-01

Full Text Available The clinical management of severe pathological conditions, such as B-cell chronic lymphocytic leukemia (B-CLL, is subject to continuous optimization and re-evaluation. Patients may fully benefit from rapid, standardized laboratory tools designed to facilitate their early stratification according to disease risk, stage and prognosis. Such technologies may also aid the clinician in selecting the therapeutic option with the greatest chances of success. The presence of specific genetic abnormalities are frequently associated with the clinical outcome of oncologic patients in general, and B-CLL patients in particular. In the current study, a group of 58 B-CLL patients were evaluated for the detection of gene copy number alterations (deletions or duplication/ amplifications within 45 distinct genetic targets, by means of a novel molecular methodology, Multiplex Ligation - Dependent Probe Amplification (MLPA. Simple or complex genetic defects were identified in 67% of cases, and the most common aberrations observed were: deletion of the short arm of chromosome 13 in 33% of cases, deletion of the long arm of chromosome 11 in 16% of cases, trisomy 12 in 16% of cases, and deletion of the short arm of chromosome 17 in 7% of cases. The main conclusion of the study presented here points towards MLPA as a potential key step of clinical management protocols in B-CLL, providing that it will be fully standardised for routine diagnosis.

Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation

International Nuclear Information System (INIS)

Ferraro, P.; Celotti, L.; Furlan, D.; Pattarello, I.; Peserico, A.

1990-01-01

DNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H-TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6-48 J/m2). DNA replication was measured in PHA-stimulated lymphocytes, UV-irradiated or mock-irradiated, by incubation with 3H-TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H-TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes

Spontaneous Apoptosis, Oxidative Status and Immunophenotype Markers in Blood Lymphocytes of AIDS Patients

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Gabriele A. Losa

2000-01-01

Full Text Available Peripheral blood mononuclear cells (PBMC from 251 HIV‐positive drug abusers of known clinical stage and from 40 healthy donors were tested for conventional immunologic markers (CD3, CD4, CD8, CD19, CD14, CD16/CD56, CD45 and HLA‐DR. Additional cell parameters and the occurrence of spontaneous apoptosis (programmed cell death were investigated on freshly isolated PBMC by flow cytometric measurement of either annexin‐V bound to plasma membrane phosphatidylserine or propidium iodide uptake. The activity of γ‐glutamyltransferase (γ‐GT, an ectoenzyme contributing to the synthesis of the intracellular antioxidant glutathione (GSH and involved in early apoptosis, was also determined in these cells. Immunocompetent T‐cell counts were lower in HIV+ patients, with the exception of CD8+ and HLA‐DR+ lymphocytes. The external binding of annexin‐V was significantly higher in HIV+ PBMC and occurred in both CD8+ and CD4+ T‐lymphocyte subsets. The activity of γ‐GT, was significantly lower in the PBMC from HIV+ patients, indicating that the redox status of PBMC may be affected in HIV+ individuals. Finally, the most dominant features characterising patients receiving antiretroviral therapy were greater long‐term stability in the distribution of various cell parameters excepted the level of apoptosis.

Quantification of cell-free DNA in blood plasma and DNA damage degree in lymphocytes to evaluate dysregulation of apoptosis in schizophrenia patients.

Science.gov (United States)

Ershova, E S; Jestkova, E M; Chestkov, I V; Porokhovnik, L N; Izevskaya, V L; Kutsev, S I; Veiko, N N; Shmarina, G; Dolgikh, O; Kostyuk, S V

2017-04-01

Oxidative DNA damage has been proposed as one of the causes of schizophrenia (SZ), and post mortem data indicate a dysregulation of apoptosis in SZ patients. To evaluate apoptosis in vivo we quantified the concentration of plasma cell-free DNA (cfDNA index, determined using fluorescence), the levels of 8-oxodG in cfDNA (immunoassay) and lymphocytes (FL1-8-oxodG index, flow cytometry) of male patients with acute psychotic disorders: paranoid SZ (total N = 58), schizophreniform (N = 11) and alcohol-induced (N = 14) psychotic disorder, and 30 healthy males. CfDNA in SZ (N = 58) does not change compared with controls. In SZ patients. Elevated levels of 8-oxodG were found in cfDNA (N = 58) and lymphocytes (n = 45). The main sources of cfDNA are dying cells with oxidized DNA. Thus, the cfDNA/FL1-8-oxodG ratio shows the level of apoptosis in damaged cells. Two subgroups were identified among the SZ patients (n = 45). For SZ-1 (31%) and SZ-2 (69%) median values of cfDNA/FL1-8-oxodG index are related as 1:6 (p DNA in the patient's body tissues and may be a contributing cause of acute psychotic disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

DNA damages induced in human lymphocytes by UV or X-rays and repair capacities of healthy donors and skin cancer patients

International Nuclear Information System (INIS)

Cebulska-Wasilewska, A.; Dyga, W.; Budzanowska, E.

1999-01-01

The aim of this study was to compare variation in the individual susceptibility of various donors to the induction of the DNA damage by genotoxic agents and their cellular capabilities to repair induced damage. DNA damages induced by UV or X-rays in lymphocytes and cellular repair capability of healthy donors and persons bearing various categories of skin cancer cells were investigated. Fresh blood was collected by venipuncture from 35 individuals (including nine prior to skin cancer treatment). All cancer patients were nonsmoking males, however 42.3 % of them were former smokers. All healthy donors were also males, an average age was 38.6 y and among them 68% were recent or former smokers. Immediately after collecting samples, lymphocytes were isolated and stored at -70 o C for further studies in vitro. Previously cryopreserved lymphocytes were defrosted and viability of the cells was investigated. The single cell gel electrophoresis assay (SCGE), known as a Comet assay, was performed in defrozen lymphocytes to evaluate individual DNA damage levels presented in lymphocytes at the time of sample's collection. To compare individual susceptibility to the induction of DNA damage by UV and ionizing radiation, lymphocytes were exposed to dose of 6 J/m 2 of UV or 2 Gy of X-rays and DNA damages were detected again with an application of the Comet assay. Additionally, to study variation in the individuals cellular capability to repair damages induced, prior to the DNA damage analysis an incubation of cells exposed was also done in presence or absence of phytohemagglutinin (cell divisions processes starting agent). Results showed in untreated lymphocytes of skin cancer patients significantly higher than in the reference group levels of the DNA damages. Significantly different responses to UV and significantly lower capabilities to repair UV induced damage in skin cancer patients were observed. On the average, no differences between reference group and skin cancer patients

Diagnostic Accuracy of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Detecting Occult Papillary Thyroid Microcarcinomas in Benign Multinodular Goitres

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Dimitrios K. Manatakis

2018-01-01

Full Text Available Objective. To investigate the diagnostic accuracy of neutrophil-to-lymphocyte (NLR and platelet-to-lymphocyte (PLR ratios in detecting occult papillary thyroid microcarcinomas in benign, multinodular goitres. Methods. 397 total thyroidectomy patients were identified from the institutional thyroid surgery database between 2007 and 2016 (94 males, 303 females, mean age 53 ± 14.5 years. NLR and PLR were calculated as the absolute neutrophil and absolute platelet counts divided by the absolute lymphocyte count, respectively, based on the preoperative complete blood cell count. Results. NLR was significantly higher in carcinomas and microcarcinomas compared to benign pathology (p=0.026, whereas a direct association could not be established for PLR. Both NLR and PLR scored low in all parameters of diagnostic accuracy, with overall accuracy ranging between 45 and 50%. Conclusions. As surrogate indices of the systemic inflammatory response, NLR and PLR are inexpensive and universally available from routine blood tests. Although we found higher NLR values in cases of malignancy, NLR and PLR cannot effectively predict the presence of occult papillary microcarcinomas in otherwise benign, multinodular goitres.

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

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Zhou, Xin; Wang, Jing; Xia, Jun; Cheng, Feng; Mao, Jingjue; Zhu, Jianwei; Guo, Hongfeng

2018-01-01

The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

The Danish National Chronic Lymphocytic Leukemia Registry

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da Cunha-Bang, Caspar; Geisler, Christian Hartmann; Enggaard, Lisbeth

2016-01-01

AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate...

Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease.

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Mercè Rosinach

Full Text Available The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned.To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS, which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology.Double-blind randomized clinical trial of gluten vs placebo rechallenge.>18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day and 7 placebo. Clinical symptoms, quality of life (GIQLI, and presence of gamma/delta+ cells and transglutaminase deposits were evaluated.91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01. Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01. The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50% patients as having probable 'coeliac lite' disease.This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet.ClinicalTrials.gov NCT02472704.

Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoieticstem cell transplantation

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Juliane Morando

2012-01-01

Full Text Available BACKGROUND: Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients. OBJECTIVE: To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival. METHODS: A descriptive, retrospective study was performed of 137 under 21-year-old patients who were submitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count 0.3 x 10(9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10(9/Land < 0.75 x 10(9/L being considered inadequate and adequate lymphocyte recovery, respectively. RESULTS: There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse. CONCLUSION: The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

Lymphocyte counts and responses to PHA and PPD following radiation therapy for breast cancer in patients who develop recurrent disease and those who remain clinically disease-free

International Nuclear Information System (INIS)

Blomgren, H.; Wasserman, J.; Wallgren, A.; Baral, E.; Petrini, B.; Idestroem, K.

1980-01-01

Peripheral blood lymphocyte counts and stimulations by PHA and PPD in vitro were examined before and up to four years after local pre- or post-operative radiation therapy of 99 patients with breast cancer. The patient material was divided into those who remained clinically disease-free during a follow up period of 4.5-7 years and those who relapsed. Radiation therapy reduced the lymphocyte counts and PPD response to the same levels in both groups of patients; there were no essential differences in their recoveries, with the exception of a somewhat delayed recovery of the PPD-response in the patients who relapsed. PHA responses of the lymphocytes were not decreased following radiation therapy. The data indicate that these radiation induced changes of the peripheral lymphocyte population were similar both in patients who relapsed and those who remained symptom free. A group of 47 women with breast cancer that was treated by surgery only was examined similarly as a comparison. Patients from this group who developed local recurrences had higher lymphocyte counts than those who remained disease-free; patients who developed distant metastases had somewhat decreased PHA responses

Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in ovarian cancer: a meta-analysis of retrospective studies.

Science.gov (United States)

Zhao, Zhe; Zhao, Xinrui; Lu, Jingjing; Xue, Jing; Liu, Peishu; Mao, Hongluan

2018-04-01

The systemic inflammatory response markers have been reported to be associated with the prognosis of various cancers. We conducted this meta-analysis of retrospective studies to evaluate and identify the prognostic impact of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on ovarian cancer. PubMed, EMBASE, and China National Knowledge Infrastructure databases were included to search for eligible studies. The following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma", "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and "ovary tumor". The random-effects model was chosen to estimate the pooled HR with 95% CI. Heterogeneity between studies was assessed by Higgins I 2 value. The stability and heterogeneity of studies were analyzed by sensitivity analysis. Publication bias was examined by Egger's test and Begg's test with the funnel plots. 13 studies consisting of 3467 patients were considered for meta-analysis. We found that the high NLR had a poor prognostic impact on OS and PFS in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI 1.48-2.12, respectively. Similarly, the results showed the high PLR adversely affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48 and HR 1.85, 95% CI 1.53-2.25, respectively. In conclusion, we found that both NLR and PLR had an unfavorable impact on PFS and OS of patients with ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective prognostic predictors of ovarian cancer.

Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

International Nuclear Information System (INIS)

Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

1982-01-01

When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

Effect of radiotherapy on lymphocyte cytotoxicity in vitro

Energy Technology Data Exchange (ETDEWEB)

Wasserman, J; Melen, B [Central Microbiological Laboratory, Stockholm County Council (Sweden); Blomgren, H; Glas, U; Perlmann, P

1975-11-01

The cytotoxic functions of highly purified blood lymphocytes from patients with breast cancer were studied before and after radiotherapy. Addition of PHA or of rabbit antibodies to target cells (chicken erythrocytes) were chosen as two means of inducing lymphocyte cytotoxicity in vitro. The proportion of T and non-T lymphocytes was determined by means of E and EAC rosette tests. The antibody-induced cytotoxicity of lymphocytes decreased following radiotherapy while that mediated by PHA remained unchanged. There was some reduction in the percentage of EAC rosette-forming cells. These results, as well as earlier observations, suggest that the decrease in the peripheral blood of the proportion of lymphocytes with receptors for activated complement is responsible for changes in the antibody-mediated lymphocyte cytotoxicity.

Investigations on DNA repair in peripheric lymphocytes of arthritic patients treated at Badgastein

International Nuclear Information System (INIS)

Egg, D.; Guenther, R.; Klein, W.; Kocsis, F.; Altmann, H.

1976-01-01

The DNA repair capacity in peripheric lymphocytes was studied in 18 arthritic patients after completion of a therapy at Badgastein. It was found that excision repair determined by the ''student test'' was significantly increased for 11 patients as compared to the level before treatment. In 4 patients no significant change was found. A clear decrease of DNA excision repair was encountered in 2 patients. One patient showed a complete inhibition of DNA excision repair before as well as after the treatment. The role of different parameters such as environmental radiaton exposure, altitude, ambient temperature for the observed changes cannot be deduced from the results obtained as yet and shall be clarified in subsequent investigation. (G.G.)

Cutaneous Mucormycosis Following a Bullous Pemphigoid Flare in a Chronic Lymphocytic Leukemia Patient on Ibrutinib.

Science.gov (United States)

Stein, Matthew K; Karri, Saradasri; Reynolds, Jackson; Owsley, Jeff; Wise, Austin; Martin, Mike G; Zare, Fereshteh

2018-04-01

While the recent development of novel therapeutics in oncology, such as small molecule kinase inhibitors (SMKIs), has enabled our ability to target disease-specific molecular pathways, the prolonged impact of these agents on the immune system and infectious risk remains to be seen. We present a 68-year-old male with refractory chronic lymphocytic leukemia (CLL) on ibrutinib monotherapy for 3 years who developed extensive cutaneous mucormycosis following a severe bullous pemphigoid (BP) flare. He received amphotericin B for 4 weeks and was continued on posaconazole with resolution of his mucormycosis infection. Consistent with a growing evidence of literature identifying opportunistic fungal infections in patients on ibrutinib therapy, providers should be cognizant of medical comorbidities that may predispose to such infections and explore methods of prevention before starting ibrutinib and other SMKIs.

Micronuclear and sister chromatid exchange analyses in peripheral lymphocytes of patients with oral lichen planus--a pilot study.

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Ergun, S; Warnakulasuriya, S; Duman, N; Saruhanoğlu, A; Sevinç, B; Oztürk, S; Ozel, S; Cefle, K; Palanduz, S; Tanyeri, H

2009-10-01

The purpose of this study was to determine the genetic instability of peripheral blood lymphocytes from patients diagnosed with oral lichen planus (OLP) by investigation of frequencies of micronuclei (MN) and sister chromatid exchange (SCE). A total of 22 newly diagnosed and untreated patients with OLP of same severity scores and twenty healthy controls participated in this study. They were all non-smokers with no previous history or family history of cancer. The periodontal status, flow rate and buffering capacity of whole mouth saliva were recorded. SCE and MN analyses were performed on peripheral blood lymphocytes of OLP patients and healthy controls. The frequencies of MN (50.00 +/- 22.36) and SCE (6.89 +/- 1.48) in OLP patients were found to be significantly elevated compared with that in normal individuals (25.20 +/- 9.52 and 5.93 +/- 1.31; z = 3.946, P = 0.0001; z = 2.346, P = 0.019). There were no significant differences in the MN frequency and SCE between the two subgroups with reticular or erosive types of OLP. These pilot data indicate an increased genomic instability in peripheral blood lymphocytes of a cohort of Turkish patients diagnosed with oral lichen planus as compared with that of healthy individuals. As patients with OLP may have an increased or potential risk for oral malignancy, these assays could be used in translational research to monitor beneficial effects of interventions and long-term prognosis.

Differences in oral habit and lymphocyte subpopulation affect malignant transformation of patients with oral precancer

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Chien-Yang Yeh

2016-04-01

Conclusion: These results suggest that age, alcohol consumption, and early activation of T cells, B cells, and natural killer cells are crucial in the malignant transformation of oral precancer. Analysis of patient's lymphocyte populations may help predict the malignant transformation of oral precancer.

T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

International Nuclear Information System (INIS)

Han, T.; Dadey, B.

1978-01-01

Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3 H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia.

Science.gov (United States)

Strati, Paolo; Uhm, Joon H; Kaufmann, Timothy J; Nabhan, Chadi; Parikh, Sameer A; Hanson, Curtis A; Chaffee, Kari G; Call, Timothy G; Shanafelt, Tait D

2016-04-01

Abroad array of conditions can lead to neurological symptoms in chronic lymphocytic leukemia patients and distinguishing between clinically significant involvement of the central nervous system by chronic lymphocytic leukemia and symptoms due to other etiologies can be challenging. Between January 1999 and November 2014, 172 (4%) of the 4174 patients with chronic lymphocytic leukemia followed at our center had a magnetic resonance imaging of the central nervous system and/or a lumbar puncture to evaluate neurological symptoms. After comprehensive evaluation, the etiology of neurological symptoms was: central nervous system chronic lymphocytic leukemia in 18 patients (10% evaluated by imaging and/or lumbar puncture, 0.4% overall cohort); central nervous system Richter Syndrome in 15 (9% evaluated, 0.3% overall); infection in 40 (23% evaluated, 1% overall); autoimmune/inflammatory conditions in 28 (16% evaluated, 0.7% overall); other cancer in 8 (5% evaluated, 0.2% overall); and another etiology in 63 (37% evaluated, 1.5% overall). Although the sensitivity of cerebrospinal fluid analysis to detect central nervous system disease was 89%, the specificity was only 42% due to the frequent presence of leukemic cells in the cerebrospinal fluid in other conditions. No parameter on cerebrospinal fluid analysis (e.g. total nucleated cells, total lymphocyte count, chronic lymphocytic leukemia cell percentage) were able to offer a reliable discrimination between patients whose neurological symptoms were due to clinically significant central nervous system involvement by chronic lymphocytic leukemia and another etiology. Median overall survival among patients with clinically significant central nervous system chronic lymphocytic leukemia and Richter syndrome was 12 and 11 months, respectively. In conclusion, clinically significant central nervous system involvement by chronic lymphocytic leukemia is a rare condition, and neurological symptoms in patients with chronic lymphocytic

Cryptococcal infections in two patients receiving ibrutinib therapy for chronic lymphocytic leukemia.

Science.gov (United States)

Stankowicz, Matthew; Banaszynski, Megan; Crawford, Russell

2018-01-01

Cryptococcal infections are responsible for significant morbidity and mortality in immunocompromised patients. Reports of these infections in patients on small molecular kinase inhibitors have not been widely reported in clinical trials. We describe one case of cryptococcal meningoencephalitis and one case of cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic lymphocytic leukemia. Despite different sites of cryptococcal infection, both patients had similar presentations of acute illness. Patient 1 was worked up for health care-associated pneumonia, as well as acute sinusitis prior to the diagnosis of cryptococcal meningoencephalitis. He also had a more complex past medical history than patient 2. Patient 2 developed atrial fibrillation from ibrutinib prior to admission for presumed health care-associated pneumonia. Cryptococcal antigen testing was done sooner in this patient due to patient receiving high-dose steroids for the treatment of underlying hemolytic anemia. We conclude that patients who develop acute illness while receiving ibrutinib should be considered for cryptococcal antigen testing.

Analysis on the change of T lymphocyte subsets and NK cells in patients with systemic lupus erythematosus

International Nuclear Information System (INIS)

Yao Yanhua; Chen Zhiwei; Deng Yingsu; Gu Guohao; Gao Chun; Yu Yunxia

2006-01-01

Objective: To investigate the relationship between the peripheral blood lymphocyte subsets, disease activity and renal impairment in patients with systemic lupus erythematosus (SLE). Methods: T lymphocyte subsets and NK cells from the peripheral blood of 78 patients who suffered SLE were measured, and then the relationship between disease activity, renal symptoms and the states of cellular immunology were analysed. Results: CD 8 + and CD 3 + cells were significantly decreased in the peripheral blood from those patients with active stage of SLE compared to remission phase, while the CD 4 + cells and CD 4 + /CD 8 + ratio did not. And NK cells, but not CD 3 + , CD 8 + cells or CD 4 + /CD 8 + and CD 8 + cells may correlate the the disease activity of SLE patients, but CD 4 + and ratio CD 4 + CD 8 + can not reflect disease activity. While the reduction of NK cells may have relationship with renal suffering. (authors)

Tumor features and correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer with Yin deficiency

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YANG Zhiyun

2016-03-01

Full Text Available ObjectiveTo investigate the tumor features and the correlation between lymphocyte count and biochemical parameters in patients with hepatitis B virus-associated primary liver cancer (PLC with yin deficiency. MethodsA total of 148 PLC patients who were treated in Beijing Ditan Hospital, Capital Medical University, from July 2013 to February 2015 were enrolled and divided into yin-deficiency PLC group (52 patients and non-yin-deficiency PLC group (96 patients. The patients′ general information and laboratory markers were collected, including oncological parameters (alpha-fetoprotein, carcinoembryonic antigen (CEA, and carbohydrate antigen 199 (CA19-9, virological parameter (HBsAg, gross type (nodular type, massive type, bulky type, and diffuse type, radiological features (main portal vein diameter, portal vein tumor thrombus, and extrahepatic metastasis, biochemical parameters (Model for End-Stage Liver Disease (MELD score, white blood cell, red blood cell, platelet (PLT, alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBil, gamma-glutamyl transpeptidase, alkaline phosphatase, albumin, cholinesterase, prothrombin time (PT, and prothrombin time activity (PTA, and lymphocyte count. The t-test was applied for comparison of normally distributed continuous data between groups, and the Pearson correlation analysis was applied for correlation analysis. The Mann-Whitney U test was applied for comparison of non-normally distributed continuous data between groups, and the Spearman correlation analysis was applied for correlation analysis. The chi-square test was applied for comparison of categorical data between groups. ResultsHBsAg showed a significant difference between the two groups (χ2=5.658, P=0.017. Compared with the non-yin-deficiency PLC group, the yin-deficiency PLC group had significantly increased CEA and CA19-9 (U=-2.200 and -2.194, both P＜0.05, significantly increased MELD score, TBil, and PT (t=2.2, U=-2.0, U=-2

Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study.

Science.gov (United States)

Löfstedt, Alexandra; Chiang, Samuel C C; Onelöv, Erik; Bryceson, Yenan T; Meeths, Marie; Henter, Jan-Inge

2015-12-01

Mutations in genes for perforin-dependent lymphocyte cytotoxicity are associated with haemophagocytic lymphohistiocytosis, a rare disease of severe hyperinflammation that typically becomes evident in early childhood. It has been suggested that individuals with hypomorphic biallelic mutations in genes associated with haemophagocytic lymphohistiocytosis are at increased risk of developing haematological malignancies. We aimed to assess whether relatives of patients with primary haemophagocytic lymphohistiocytosis (ie, heterozygous carriers of these mutated genes) were more likely to develop cancer. In this retrospective cohort study, we used a multigeneration registry to identify relatives (parents and grandparents) of 79 Swedish children (Karolinska Institutet Research Foundation, Stockholm County Council (ALF-project). Copyright © 2015 Elsevier Ltd. All rights reserved.

Diagnosis of large granular lymphocytic leukemia in a patient previously treated for acute myeloblastic leukemia

OpenAIRE

Sinem Civriz Bozdag; Sinem Namdaroglu; Omur Kayikci; Gülsah Kaygusuz; Itir Demiriz; Murat Cinarsoy; Emre Tekgunduz; Fevzi Altuntas

2013-01-01

Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia.

Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

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Pavlica Ljiljana

2003-01-01

Cl. Bacteriology: Chlamydia trachomatis was isolated by cell culture using cycloheximide-treated McCoy cells [10], while Ureaplasma urealyticum was identified according to its biochemical properties grown on cell-free liquid medium [9]. RESULTS Proliferative response of the PB lymphocytes to stimulation by mitogen and ureaplasma antigen did not differ between RS and RA patients. Also, there was no difference in proliferative response of SF lymphocytes to mitogen stimulation between RS and RA patients (Figure 1. However, proliferation of SF lymphocytes stimulated by ureaplasma antigen was significantly elevated in RS patients compared with the control group. This difference is statistically significant (p<0.05 (Figure 2. Difference in proliferative response of the PB and SF lymphocytes stimulated by the ureaplasma antigen was not found in RS patients. DISCUSSION It was found that SF lymphocytes of RS patients showed significantly elevated proliferative response to stimulation by the ureaplasma antigen compared with SF lymphocytes of the control group. There was no difference when the lymphocytes were stimulated by the mitogen. Our findings suggest that elevated proliferative response of lymphocytes is the sign of stimulation cell-mediated immunity to antigen present in inflamed joint. Hence, the main immune response to Ureaplasma is on the cell-mediated level in the affected joint. This confirms the earlier finding reported by Ford et all. who concluded that synovial rather than peripheral blood lymphocytes indicate the microbiological cause of arthritis [11,12]. Horowitz etal. demonstrated the correlation between clinical remission after antibiotic therapy and eradication of Ureaplasma, together with a decrease in cellular immune response synovial fluid lymphocytes to ureaplasma antigen stimulation [13]. In that study Horowitz did not find statisticaly significant difference of ureaplasma proliferative response between PB and SF lymphocytes in patients with RS. We obtained the

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib

OpenAIRE

Okamoto, Koh; Proia, Laurie A.; Demarais, Patricia L.

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. It acts by inhibitin...

Platelet indices and platelet-to-lymphocyte ratio predict coronary chronic total occlusion in patients with acute ST-elevation myocardial infarction

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Hadadi Laszlo

2015-12-01

Full Text Available Coronary chronic total occlusion (CTO is caused by organized thrombi or atherosclerotic plaque progression. The presence of a CTO is an independent predictor of mortality in patients presenting with ST-segment elevation myocardial infarction (STEMI. Platelets have a crucial role in the pathophysiology of atherosclerosis. The aim of this retrospective study was to investigate platelet indices as predictors of CTO in patients with STEMI treated with primary percutaneous coronary intervention (pPCI. A total number of 334 patients admitted for STEMI between January 2011 and December 2013 were included and divided in two groups based on the presence of CTO (48 patients in CTO+ group, 286 patients in CTO-group. Platelet count, mean platelet volume (MPV, platelet distribution width (PDW, platelet-large cell ratio (P-LCR, lymphocyte and neutrophil count determined on admission were analyzed. MPV was larger in patients with CTO compared with patients without CTO (p=0.02, as were PDW (p=0.03 and P-LCR (p=0.01. Platelet-to-lymphocyte ratio (PLT/LYM was lower in patients with CTO: 105.2 (75.86-159.1 compared to 137 (97-188.1, p<0.01. Receiver-operator characteristic curve analysis identified an area under the curve of 0.61 (95%CI=0.57-0.67, p< 0.01 for PLT/LYM in predicting the presence of a CTO, with a cut-off value at 97.73. Lower values than this were independent predictors of a CTO in multivariate logistic regression analysis, with an Odds Ratio of 2.2 (95%CI=1.15-4.20, p=0.02. Our results support the use of platelet indices and PLT/LYM as predictors of CTO in patients presenting with STEMI.

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp

DEFF Research Database (Denmark)

Nielsen, Jeppe Sylvest; A, Larsson; Brix-Christensen, Vibeke

2005-01-01

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors...... hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis...... sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number...

Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis.

Science.gov (United States)

Al-Mossawi, M H; Chen, L; Fang, H; Ridley, A; de Wit, J; Yager, N; Hammitzsch, A; Pulyakhina, I; Fairfax, B P; Simone, D; Yi, Yao; Bandyopadhyay, S; Doig, K; Gundle, R; Kendrick, B; Powrie, F; Knight, J C; Bowness, P

2017-11-15

Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A + GM-CSF + double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF + CD4 + cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF + and IL-17A + GM-CSF + double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.

2,3,7,8-tetrachlorodibenzo-p-dioxin decrease expression of aryl hydrocarbon receptor in peripheral lymphocyte of β-thalassemia major patients.

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Ghatrehsamani, Mahdi; Soleimani, Masoud; Esfahani, Behjat Al-Sadat Moayedi; Hakemi, Mazdak Ganjalikhani; Shirzad, Hedayatollah; Eskandari, Nahid; Adib, Minoo

2015-01-01

β-thalassemia major is a hereditary disease with inefficient erythropoiesis. Level of inflammatory cytokine is elevated in these patients. In this study, we investigate the effect of aryl hydrocarbon receptor (AhR) ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on the expression of inflammatory mediators in β-thalassemia major patient's lymphocytes. Peripheral blood mononuclear cells of patients and healthy participants was isolated and cultured in favor of lymphocytes increment. Based on the treatment, we divided the cell into four groups. The orders of group's treatments were no treatment, tumor necrosis factor-α (TNF-α) treatment, TNF-α and TCDD treatment, TCDD treatment in Group 1-4, respectively. After cell culture, we extracted the cells RNA and converted them to cDNA. Real-time polymerase chain reaction was performed to assessment relative expression of caspase-1, NLRP3, and AhR. We compared all patient groups with equal healthy (control) groups. Results showed that expression of caspase-1 in patients (Groups 1 and 2) was significantly lower than healthy individuals (P 0.05). Expression of AhR in other groups of patients (3 and 4) was significantly lower than control groups (P < 0.05). Expression of caspase-1 in Group 4 was significantly larger than the control group (P < 0.001). We show here that chronic inflammation decrease caspase-1 expression and exposure of human lymphocytes to TCDD promote caspase-1 expression. Furthermore, activation of AhR with TCDD decreases AhR expression in lymphocytes of β-thalassemia major disease.

Ibrutinib Improves Survival in Patients with Previously Treated Chronic Lymphocytic Leukemia

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A summary of results from an international phase III trial that compared ibrutinib (Imbruvica®) and ofatumumab (Arzerra®) for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies.

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Williams, AnnaLynn M; Baran, Andrea M; Meacham, Philip J; Feldman, Megan M; Valencia, Hugo E; Newsom-Stewart, Catherine; Gupta, Nealansh; Janelsins, Michelle C; Barr, Paul M; Zent, Clive S

2018-03-01

We studied the risk of infections in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Major infections were defined as requiring hospital admission or intravenous antimicrobial treatment. Incidence rate (IR) ratios (IRR) were used to compare infection rates. Of 263 CLL patients followed for 936.9 person-years, 60% required treatment for progressive CLL (66 received ibrutinib). Infections occurred in 71.9% patients (IR 92.4/100 person-years) with 31.9% having major infections (IR 20.3/100 person-years) and infections causing 37.5% of deaths. CLL treatment was associated with significantly higher risk of major (IRR 3.31, 95% CI 2.10, 5.21) and minor (IRR 1.78, 95% CI 1.43, 2.22) infections. Compared to their previous chemoimmunotherapy patients receiving salvage ibrutinib therapy (n = 47) had a significantly increased risk of a major infection (IRR 2.35 95% CI 1.27, 4.34). The risk of infection in CLL patients remains high even with use of less immunosuppressive therapies.

Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation

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Bredberg, A.; Lambert, B.; Lindblad, A.; Swanbeck, G.; Wennersten, G.

1983-01-01

Exposure of human lymphocytes and skin fibroblasts in vitro to a single, clinically used dose of PUVA, i.e., 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 0.9-4 J/cm2 of longwave ultraviolet radiation (UVA), lead to the formation of DNA damage as determined by alkaline elution, and to chromosome aberrations and sister chromatid exchanges (SCE). When lymphocyte-enriched plasma was obtained from psoriasis patients 2 h after oral intake of 8-MOP and then UVA irradiated (1.8-3.6 J/cm2) in vitro, an increased frequency of chromosome aberrations and SCE was observed. Normal levels of chromosome aberrations and SCE were found in lymphocytes of psoriasis patients after 3-30 weeks of PUVA treatment in vivo. A small but statistically significant increase in the SCE frequency was observed in the lymphocytes of psoriasis patients treated for 1-6 years with PUVA (mean 18.0 SCE/cell) as compared with before PUVA (mean 15.8, p less than 0.05). Skin fibroblasts of psoriasis patients analyzed 5 years after the start of PUVA treatment showed a normal number of SCE but a high fraction of filter-retained DNA in the alkaline elution assay, suggesting the presence of cross-linked DNA

Therapeutic Vaccine Against HIV, Viral Variability, Cytotoxic T Lymphocyte Epitopes, and Genetics of Patients.

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Fleury, Herve; Tumiotto, Camille; Bellecave, Pantxika; Recordon-Pinson, Patricia

2018-01-01

The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles. There is a need to find a balance between the conservation of cytotoxic T lymphocyte (CTL) epitopes and presentation by HLA alleles. The pathway is a narrow one between adaptation of the virus to HLA I restriction and the definition of conserved proviral CTL epitopes presentable by HLA I alleles. It is likely that the genetics of patients will need to be considered for HIV-1 vaccine studies and that multidisciplinary collaboration will be essential in this field of infectious diseases.

Cytogenetic effect of 153 Sm-EDTMP in peripheral lymphocytes of patients with metastatic cancer

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Silva, Marcia Augusta da

2001-01-01

The 153 Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of 153 Sm-EDTMP at cellular level. The present study was conduced with the aim of evaluating the cytogenetic effects of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique, either in vivo or in vitro. For that, the blood samples were collected before and one hour after the endovenous administration of 153 Sm-EDTMP (mean activity of 42.53+/-5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before 153 Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with 153 Sm-EDTMP, did not influence these parameters. The carrier molecule, EDTMP, did not influence the induction of chromosome aberration. In relation to the in vitro assays, the obtained data of peripheral lymphocytes of healthy donors and patients with no previous treatment exposed to different radioactive concentration of 153 Sm-EDTMP (0.046 - 1.110 MBq/mL) were better adjusted by linear regression model (Y=A+BX). The chromosome damage induced by 153 Sm-EDTMP observed in vitro was about 2 fold higher than that found in vivo for the group of patients with no previous treatment. The obtained data showed that the therapy with 153 Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes on hour after its administration in

Comparison of T stage, N stage, multifocality, and bilaterality in papillary thyroid carcinoma patients according to the presence of coexisting lymphocytic thyroiditis.

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Park, Jin Young; Kim, Dong Wook; Park, Ha Kyung; Ha, Tae Kwun; Jung, Soo Jin; Kim, Do Hun; Bae, Sang Kyun

2015-01-01

This study aimed to assess the relationship between coexisting lymphocytic thyroiditis and T-N stages of papillary thyroid carcinoma (PTC) by histopathological analysis. The study included 653 patients who underwent thyroid surgery for PTC at our hospital. Each case was classified as either Hashimoto's thyroiditis (HT), non-Hashimoto type of lymphocytic thyroiditis (NHLT), or normal according to the histopathology of thyroid parenchyma. Patient age, gender, surgical modality, location, T stage, N stage, multifocality and bilaterality were compared according to the histopathology. The prevalence of coexisting lymphocytic thyroiditis was 25.8% (169/653); HT (7.5%, 49/653) and NHLT (18.3%, 120/653). There were no significant differences in T stage, N stage, multifocality and bilaterality with regard to coexisting lymphocytic thyroiditis, regardless of whether HT and NHLT were considered collectively or discretely. Primary tumor size (p thyroiditis did not differ from those with normal parenchyma in terms of T stage, N stage, multifocality and bilaterality.

Sickle cell anemia induces changes in peripheral lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in patients under treatment.

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Castilhos, Lívia G; Doleski, Pedro H; Bertoldo, Tatiana M D; Passos, Daniela F; Bertoncheli, Claudia de M; Rezer, João F P; Schlemmer, Josiane B; Leal, Daniela B R

2015-07-01

Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that results in sickle-shaped red blood cells. The vascular obstruction by sickle erythrocytes is often inflammatory, and purinergic system ecto-enzymes play an important role in modulating the inflammatory and immune response. This study aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA treated patients, as well as verify the cytokine profile in this population. Fifteen SCA treated patients and 30 health subjects (control group) were selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated from clot formation for the cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA (adenosine as substrate) activities were increased in lymphocytes from SCA patients (PADA enzymes represent an important control of purine-mediated in the SCA disease, avoiding elevated adenosine levels in the extracellular medium and consequent organ injuries in these patients. The pro-inflammatory cytokines decreased levels by use of hydroxyurea occur in attempt to reduce the pro-inflammatory response and prevent vaso-oclusive crisis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Concept Elicitation Within Patient-Powered Research Networks: A Feasibility Study in Chronic Lymphocytic Leukemia.

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McCarrier, Kelly P; Bull, Scott; Fleming, Sarah; Simacek, Kristina; Wicks, Paul; Cella, David; Pierson, Renee

2016-01-01

To explore the feasibility of using social media-based patient networks to gather qualitative data on patient-reported outcome (PRO) concepts relevant to chronic lymphocytic leukemia (CLL). Between August and November 2013, US-residing members of the PatientsLikeMe online CLL patient community completed open-ended web-based surveys designed to elicit descriptions of CLL symptoms, impacts, and treatment-related perceptions. Qualitative telephone follow-up interviews were conducted with a subsample of respondents. Survey responses and interview transcripts were coded for qualitative analysis using Atlas.ti. Fifty survey responses were included in the analyses. Participants were age 60.5 ± 6.9 years, 54% female, and 96% white. When surveyed, 20% were receiving current treatment, 16% were in remission, and 64% were treatment-naïve. Among respondents, 369 descriptions of CLL symptoms were coded. Fatigue-related symptoms were expressed most frequently, with 54% reporting "fatigue," "tiredness," or both in their responses. These concepts were followed by night sweats (38%), swollen lymph nodes (32%), and frequent infections (28%). Among impacts of CLL, worry and fear (66% of respondents), depressed feelings (52%), and work limitations (50%) were noted most frequently. Survey results identified constitutional symptoms of CLL included in existing PRO instruments and the literature. Although the findings suggest that qualitative data obtained through social media applications can be potentially useful in supporting concept identification for newly developed PRO instruments, they also indicate that online approaches alone may not be sufficient to achieve efficient and exhaustive concept elicitation. Further research is needed to identify whether the results can support content validity in the same way as established qualitative research methods. Copyright © 2016. Published by Elsevier Inc.

Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)

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Bordón, Elisa; Henríquez-Hernández, Luis Alberto; Lara, Pedro C; Ruíz, Ana; Pinar, Beatriz; Rodríguez-Gallego, Carlos; Lloret, Marta

2010-01-01

Head and neck cancer is treated mainly by surgery and radiotherapy. Normal tissue toxicity due to x-ray exposure is a limiting factor for treatment success. Many efforts have been employed to develop predictive tests applied to clinical practice. Determination of lymphocyte radio-sensitivity by radio-induced apoptosis arises as a possible method to predict tissue toxicity due to radiotherapy. The aim of the present study was to analyze radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients and to explore their role in predicting radiation induced toxicity. Seventy nine consecutive patients suffering from head and neck cancer, diagnosed and treated in our institution, were included in the study. Toxicity was evaluated using the Radiation Therapy Oncology Group scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis increased in order to radiation dose and fitted to a semi logarithmic model defined by two constants: α and β. α, as the origin of the curve in the Y axis determining the percentage of spontaneous cell death, and β, as the slope of the curve determining the percentage of cell death induced at a determined radiation dose, were obtained. β value was statistically associated to normal tissue toxicity in terms of severe xerostomia, as higher levels of apoptosis were observed in patients with low toxicity (p = 0.035; Exp(B) 0.224, I.C.95% (0.060-0.904)). These data agree with our previous results and suggest that it is possible to estimate the radiosensitivity of peripheral blood lymphocytes from patients determining the radiation induced apoptosis with annexin V/propidium iodide staining. β values observed define an individual radiosensitivity profile that could predict late toxicity due to radiotherapy

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

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Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

Tularemia live vaccine effect of contrasuppression of blood lymphocytes in patients with cancer of corpus uteri during combined treatment and later

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Movsesyan, M.A.; Adamyan, R.T.; Markosyan, K.M.

1999-01-01

A significant decrease in the percentage of women showing contrasuppression of blood lymphocytes, as compared with control, was identified (p ≤ 0.1); it was particularly low at terminal stage (III - IV). Surgery and subsequent radiotherapy were followed by further inhibition, particularly in terminally-ill patients. Two or three years after treatment the numbers of patients in all stage groups, showing contrasuppression increased reaching the initial, i.e. lower than normal levels. However, contrasuppression induces rose to normal in patients immunized with tularemia live vaccine (p ≥ 0.05). This effect was observed in patients of all stage groups, immunized prior to treatment, on days 15 - 20 after immunization. Normal levels of contrasuppression were maintained during treatment and 2 - 3 years on. Both contrasuppression level and stage of tumor may serve as a criterion of gravity of disease and prognosis [ru

Allogeneic stem cell transplant in patients with chronic lymphocytic leukemia with 17p deletion: consult-transplant versus consult- no-transplant analysis.

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Poon, Michelle L; Fox, Patricia S; Samuels, Barry I; O'Brien, Susan; Jabbour, Elias; Hsu, Yvonne; Gulbis, Alison; Korbling, Martin; Champlin, Richard; Abruzzo, Lynne V; Bassett, Roland L; Khouri, Issa F

2015-03-01

Allogeneic stem cell transplant (alloSCT) can overcome the adverse prognosis of chronic lymphocytic leukemia with 17p deletion (17p- CLL). However, its applicability remains unclear. Since 2007, our leukemia service has referred patients with 17p- CLL for alloSCT at presentation. In this study, the outcomes of these patients were reviewed retrospectively to determine whether they underwent alloSCT and why patients did not undergo alloSCT. Fifty-two patients with 17p- CLL who were referred to the transplant service from 2007 to 2010 were identified. Of these patients, 32 (62%) did not undergo alloSCT, mainly because of treatment- or disease-related complications (n = 15). The 2-year post-referral overall survival rates of the alloSCT and non-SCT groups were 64% and 25%, respectively (p = 0.001). These findings suggest that while alloSCT is an effective therapy in patients with 17p- CLL, pre-SCT complications may preclude a significant proportion of patients from undergoing the procedure.

Imatinib treatment induces CD5+ B lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia.

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Silvia Catellani

Full Text Available Imatinib mesylate is a first line treatment of Chronic Myelogenous Leukemia and of a rare form of gastrointestinal stromal cancer, where the response to the drug is also linked to the immune system activation with production of antineoplastic cytokines. In this study, forty patients in the chronic phase of disease, treated with imatinib mesylate, were analyzed. Bone marrow aspirates were drawn at diagnosis, after 3, 6, 12, 18 months for haematological, cytofluorimetric, cytogenetic, biomolecular evaluation and cytokine measurement. Responder and non responder patients were defined according to the European LeukemiaNet recommendations. In responder patients (n = 32, the percentage of bone marrow CD20(+CD5(+sIgM(+ lymphocytes, and the plasma levels of IgM, were significantly higher, at 3 months and up to 9 months, than in non responders. These IgM reacted with O-linked sugars expressed by leukemic cells and could induce tumor cell apoptosis. In responder patients the stromal-derived factor-1 and the B-lymphocyte-activating factor of the tumor necrosis factor family significantly raised in the bone marrow after imatinib administration, together with the bone morphogenetic proteins-2 and -7. All patients with high number of CD20(+CD5(+sIgM(+ cells and high stromal-derived factor-1 and B lymphocyte activating factor levels, underwent complete cytogenetic and/or molecular remission by 12 months. We propose that CD20(+CD5(+sIgM(+ lymphocytes producing anti-carbohydrate antibodies with anti-tumor activity, might contribute to the response to imatinib treatment. As in multivariate analysis bone marrow CD20(+CD5(+sIgM(+ cells and stromal-derived factor-1 and B-lymphocyte-activating factor levels were significantly related to cytogenetical and molecular changes, they might contribute to the definition of the pharmacological response.

Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

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Ordonez, R.; Federico, M. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C. [Hospital Universitario de Gran Canaria Dr. Negrin, Radiation Oncology Department, Las Palmas de Gran Canaria (Spain); Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Valenciano, A. [Instituto Canario de Investigacion del Cancer (ICIC), Santa Cruz de Tenerife (Spain); Bordon, E. [Universidad de Las Palmas de Gran Canaria, Clinical Sciences Department, Las Palmas de Gran Canaria (Spain); Rodriguez-Gallego, C. [Hospital Universitario de Gran Canaria Dr. Negrin, Immunology Department, Las Palmas de Gran Canaria (Spain)

2014-02-15

A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients

International Nuclear Information System (INIS)

Ordonez, R.; Federico, M.; Henriquez-Hernandez, L.A.; Pinar, B.; Lloret, M.; Lara, P.C.; Valenciano, A.; Bordon, E.; Rodriguez-Gallego, C.

2014-01-01

A close relationship exists between immune response and tumor behavior. This study aimed to explore the associations between radiation-induced apoptosis (RIA) in peripheral blood lymphocytes (PBL) and clinical pathological variables. Furthermore, it assessed the role of RIA as a prognostic factor for survival in cervical carcinoma patients. Between February 1998 and October 2003, 58 consecutive patients with nonmetastatic, localized stage I-II cervical carcinoma who had been treated with radiotherapy (RT) ± chemotherapy were included in this study. Follow-up ended in January 2013. PBL subpopulations were isolated and irradiated with 0, 1, 2 and 8 Gy then incubated for 24, 48 and 72 h. Apoptosis was measured by flow cytometry and the ss value, a parameter defining RIA of lymphocytes, was calculated. Mean follow-up duration was 111.92 ± 40.31 months. Patients with lower CD8 T lymphocyte ss values were at a higher risk of local relapse: Exp(B) = 5.137, confidence interval (CI) 95 % = 1.044-25.268, p = 0.044. Similar results were observed for regional relapse: Exp(B) = 8.008, CI 95 % = 1.702-37.679, p = 0.008 and disease relapse: Exp(B) = 6.766, CI 95 % = 1.889-24.238, p = 0.003. In multivariate analysis, only the CD8 T lymphocyte ss values were found to be of prognostic significance for local disease-free survival (LDFS, p = 0.049), regional disease-free survival (RDFS, p = 0.002), metastasis-free survival (MFS, p = 0.042), disease-free survival (DFS, p = 0.001) and cause-specific survival (CSS p = 0.028). For the first time, RIA in CD8 T lymphocytes was demonstrated to be a predictive factor for survival in cervical carcinoma patients. (orig.)

Mean Platelet Volume and Neutrophil-to-Lymphocyte Ratio in Patients with Crimean–Congo Hemorrhagic Fever

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Derya Koçer

2015-01-01

Full Text Available Objectives: Crimean–Congo hemorrhagic fever (CCHF is a tick-borne zoonotic infection caused by Crimean Congo hemorrhagic fever virus (CCHFV. The aim of the present study was to investigate the association between blood neutrophil-to-lymphocyte ratio (NLR and mean platelet volume (MPV which are simple markers of subclinical inflammation and CCHF. We also investigated the relationship of these markers with coagulation parameters.Methods: Thirty-one suspected CCHF patients, who submitted to Training and Research Hospital, Kayseri, Turkey between 2009 and 2013, were evaluated retrospectively. Among thirty-one patients, nineteen were laboratory confirmed CCHF patients diagnosed by RT-PCR or CCHFV-specific IgM positivity. Alanine aminotransferase (ALT, aspartate aminotransferase (AST, lactate dehydrogenase (LDH, creatinin phosphokinase (CK, coagulation parameters, white blood cell counts (WBCs, and platelet counts of patient group were compared with twenty-five healthy individuals.Results: MPV, AST, ALT, LDH, CK and coagulation parameters were significantly higher in patients with CCHF than the controls, whereas WBCs, neutrophil, lymphocyte, hemoglobin, platelet counts and NLR were significantly lower (p<0.05. We found no significant correlation between MPV, NLR and coagulation parameters.Conclusions: Our study demonstrates that MPV and NLR may be beneficial markers in the diagnosis of CCHF. But these parameters should not be considered stand-alone tests for this use owing to nonspecificity with other diseases.

Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia.

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Aktürk, Semra; Büyükavcı, Raikan

2017-08-01

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and systemic symptoms. The aetiology and pathogenesis of fibromyalgia are not yet fully understood. Blood neutrophil/lymphocyte ratio (NLR) is a marker of systemic inflammatory response. Platelet distribution width (PDW) and mean platelet volume (MPV) are the determinants of platelet activation and studied as markers in inflammatory diseases. The aim of the present study was to evaluate levels of NLR,PDW and MPV in patients with fibromyalgia. A total of 197 FMS patients and 53 healthy controls are included in the study. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein, neutrophil, lymphocyte and platelet counts, platelet distribution width and mean platelet volume levels were recorded. In the patient group, the blood NLR and MPV were significantly higher and the PDW was significantly lower compared to the control group. In the roc curve analysis, blood PDW ≥had 90.4% sensitivity and 90% specificity in predicting fibromyalgia. The results of this study suggest NLR and PDW as promising inflammatory markers indicating fibromyalgia and may be beneficial in facilitating the diagnosis of FMS patients.

Neutrophil-to-lymphocyte ratio in predicting prognosis and course of community community-acquired pneumonia in hospitalized patients.

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T. O. Pertseva

2018-04-01

Full Text Available Currently, a marker which could be used both to assess the severity of community acquired pneumonia (CAP and determine the risk of complications is being searched. According to some authors, Neutrophil-to-Lymphocyte Ratio (NLR could be such a marker. Therefore, the aim of our research was to determine the diagnostic significance of NLR in patients with CAP and to establish the relationship of NLR with other clinical and laboratory parameters. We conducted a retrospective analysis of 171 case histories of patients with CAP of 3 and 4 clinical groups, with the calculation of NLR (according to the common blood count. In the course of the work, it was found that NLR reflects a balance between the response of neutrophils and lymphocytes and this parameter is associated with the severity of systemic inflammation in patients with CAP. NLR has good diagnostic value in determining the mortality risk in patients with CAP, specially an increase in the level of NLR (more than 10 is associated with a high risk of life-threatening complications.

The effect of chronic lymphocytic thyroiditis on patients with thyroid cancer.

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Zhang, Yi; Ma, Xiao-Peng; Deng, Fu-Sheng; Liu, Zheng-Rong; Wei, Hou-Qing; Wang, Xi-Hong; Chen, Hao

2014-09-01

The purpose of this study was to investigate the association between chronic lymphocytic thyroiditis (CLT) and malignant tumors of the thyroid. A retrospective review of 647 patients who underwent thyroid surgery at the Department of Breast and Thyroid Surgery in Anhui Provincial Hospital, China in 2012 was performed. The clinicopathological characteristics of patients with thyroid malignancies and CLT were collected. CLT was diagnosed by histopathological method. Among 647 patients, 144 patients had thyroid malignancies and 108 patients had been diagnosed with CLT. Moreover, in total, 44 patients had thyroid malignancies coexistent with CLT: forty-one (93.2%) patients had been diagnosed with the papillary thyroid cancer (PTC); two (4.5%) patients suffered from medullary carcinoma; and one (2.3%) patient suffered from lymphoma. The morbidity of thyroid malignancies in patients with CLT was significantly higher than that in patients without CLT (40.7% versus 18.6%; P CLT compared with those without CLT (P CLT and without CLT. Female predominance was observed in patients with CLT. CLT may have no effect on the progression of thyroid malignant tumor. Nevertheless, the influences of CLT on the prognosis of the thyroid carcinoma still need to be investigated with a larger sample size.

The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients

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Matteo Piciucchi

2017-03-01

Full Text Available Different inflammation-based scores such as the neutrophil/lymphocyte ratio (NLR, the Odonera Prognostic Nutritional Index (PNI, the Glasgow Prognostic Score, the platelet/lymphocyte ratio, and the C-reactive protein/albumin ratio have been found to be significantly associated with pancreatic cancer (PDAC prognosis. However, most studies have investigated patients undergoing surgery, and few of them have compared these scores. We aimed at evaluating the association between inflammatory-based scores and PDAC prognosis. In a single center cohort study, inflammatory-based scores were assessed at diagnosis and their prognostic relevance as well as that of clinic-pathological variables were evaluated through multiple logistic regression and survival probability analysis. In 206 patients, age, male sex, tumor size, presence of distant metastasis, access to chemotherapy, and an NLR > 5 but not other scores were associated with overall survival (OS at multivariate analysis. Patients with an NLR < 5 had a median survival of 12 months compared to 4 months in those with an NLR > 5. In the 81 patients with distant metastasis at diagnosis, an NLR > 5 resulted in the only variable significantly associated with survival. Among patients with metastatic disease who received chemotherapy, the median survival was 3 months in patients with an NLR > 5 and 7 months in those with an NLR < 5. The NLR might drive therapeutic options in PDAC patients, especially in the setting of metastatic disease.

In Vitro Lymphocyte Stimulation by Simonsiella in Patients with Oral Lichen Planus

OpenAIRE

Sananmuang, K.; Pankhurst, C. L.; Gilkes, J. J. H.; Hardie, J. M.; Ivanyi, L.

2011-01-01

The relationship between cell-mediated immunity to sonicated whole cell extract of Simonsiella and lichen planus was investigated in 15 patients with lichen planus, 14 control diseases subjects and 14 controls with healthy oral mucosa by in vitro lymphocyte stimulation. The mean stimulation index was highest in lichen planus group (SI=13.8 ± 2.98), followed by the control diseases group (SI=10.9 ± 2.03) and finally by healthy control group (SI=7.2 ± 1.67). However, there ...

Leukemia -- Chronic T-Cell Lymphocytic

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... social workers, and patient advocates. Cancer.Net Guide Leukemia - Chronic T-Cell Lymphocytic Introduction Statistics Risk Factors Symptoms and Signs Diagnosis Stages Treatment Options About Clinical Trials Latest Research ...

Cardiac Surgery Outcomes in Patients With Chronic Lymphocytic Leukemia.

Science.gov (United States)

Zhu, Yuanjia; Toth, Andrew J; Lowry, Ashley M; Blackstone, Eugene H; Hill, Brian T; Mick, Stephanie L

2018-04-01

Surgical outcomes of patients with chronic lymphocytic leukemia (CLL) undergoing cardiac surgery are limited. Our objectives were to investigate hospital morbidity and mortality after open cardiac surgery in CLL versus non-CLL patients. From May 1995 to May 2015, 157 patients with CLL and 55,917 without and older than 47 years underwent elective cardiac surgery at Cleveland Clinic. By Rai criteria, 79 CLL patients (56%) were low risk (class 0), 13 (9.1%) intermediate risk (classes I and II), and 38 (27%) high risk (classes III and IV); 12 (8.5%) were in remission. Mean age of CLL patients was 72 ± 9.0 years, and 18% were women. CLL patients were propensity-score matched to 3 non-CLL patients to compare surgical outcomes. High-risk CLL patients received more blood products than matched non-CLL patients (33/38 [87%] versus 74/114 [65%], p = 0.01), but were less likely to receive cryoprecipitate (0% versus 15/114 [13%], p = .02). Intermediate-risk CLL patients received more platelet units, mean 12 versus 4.6 (p = 0.008). Occurrence of deep sternal wound infection (0% versus 5/471 [1.1%]), septicemia (5/157 [3.2%] versus 14/471 [3.0%]), and hospital mortality (4/157 [2.5%] versus 14/471 [3.0%]) were similar (p > 0.3), independent of prior chemotherapy treatment for CLL. Although CLL patients did not have higher hospital mortality than non-CLL patients, high-risk CLL patients were more likely to receive blood products. Risks associated with transfusion should be considered when evaluating CLL patients for elective cardiac surgery. Appropriate preoperative management, such as blood product transfusions, and alternative treatment options that decrease blood loss, should be considered for high-risk patients. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Phenotypic characterization of lymphocytes in HCV/HIV co-infected patients.

LENUS (Irish Health Repository)

Roe, Barbara

2009-02-01

While hepatitis C virus (HCV)-specific immune responses are attenuated in HCV\\/HIV co-infected patients compared to those infected with HCV alone, the reasons for this remain unclear. In this study, the proportions of regulatory, naïve, and memory T cells, along with chemokine receptor expression, were measured in co-infected and mono-infected patients to determine if there is an alteration in the phenotypic profile of lymphocytes in these patients. HCV\\/HIV co-infected patients had increased proportions of CD4(+) naïve cells and decreased proportions of CD4(+) effector cells when compared to HCV mono-infected patients. The proportions of CD4(+) Tregs and CD4(+) CXCR3(+) T cells were also significantly lower in co-infected patients. A decrease in CD4(+) Tregs and subsequent loss of immunosuppressive function may contribute to the accelerated progression to liver disease in co-infected individuals. Dysregulation of immune responses following reduction in the proportions of CD4(+) CXCR3(+) Th-1 cells may contribute to the reduced functional capacity of HCV-specific immune responses in co-infected patients. The findings of this study provide new information on the T-cell immunophenotype in HCV\\/HIV co-infected patients when compared to those infected with HCV alone, and may provide insight into why cell-mediated immune responses are diminished during HCV infection.

Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma.

Science.gov (United States)

Chen, Xue; Zhang, Yang; Wang, Fang; Wang, Mangju; Teng, Wen; Lin, Yuehui; Han, Xiangping; Jin, Fangyuan; Xu, Yuanli; Cao, Panxiang; Fang, Jiancheng; Zhu, Ping; Tong, Chunrong; Liu, Hongxing

2017-11-01

Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc-13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X-linked inhibitor of apoptosis. Mutations were observed in 24 (26.67%) patients; 16 patients exhibited mutations in UNC13D, 7 exhibited PRF1 mutations, and 1 exhibited monoallelic mutation in STX11. UNC13D c.2588G>A/p.G863D mutation was detected in 9 patients (10.00%) and in 4/210 controls (1.90%). This mutation was predicted to be pathogenic and it predominantly existed in the Chinese population. These findings suggest that impaired cytotoxic machinery may represent a predisposing factor for the development of lymphoma. Furthermore, these data describe a distinct mutation spectrum in Chinese patients with lymphoma, whereby UNC13D is the most frequently mutated gene. In addition, these findings suggest UNC13D c.2588G>A mutation is a founder mutation in Chinese patients.

Association of inclusion body myositis with T cell large granular lymphocytic leukaemia

DEFF Research Database (Denmark)

Greenberg, Steven A; Pinkus, Jack L; Amato, Anthony A

2016-01-01

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we...... prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD......57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present...

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

Science.gov (United States)

Soldevila, Berta; Alonso, Núria; Martínez-Arconada, Maria J; Granada, Maria L; Boada, Aram; Vallejos, Virginia; Fraile, Manuel; Fernández-Sanmartín, Marco A; Pujol-Borrell, Ricardo; Puig-Domingo, Manel; Sanmartí, Anna; Martínez-Cáceres, Eva M

2013-04-01

One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT. © 2012 Blackwell Publishing Ltd.

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

Science.gov (United States)

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Influence of neutrophile granulocyte/lymphocyte ratio (NLR on poor prognosis of elderly AECOPD patients during hospital stay

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Jian-Rong Cui

2016-01-01

Full Text Available Objective: To discuss the influence of neutrophile granulocyte/lymphocyte ratio(NLR to the poor prognosis of elderly AECOPD patients during the stay in hospital. Method: A total of 133 cases elderly patients with AECOPD admitted in our hospital from March 2013 to September 2014 were selected, and divided them into death group (31 cases and survival group (102 cases according to in-hospital death occurrence; To compare the on admission general clinical data, therapy method, lung function, blood routine examination [white blood cell count (WBC, neutrophile granulocyte/lymphocyte ratio(NLR], C-reactive protein (CRP, blood gas analysis and blood biochemical indexes in both groups, and drew ROC curve for a analysis of the clinical value of NLR in the prediction of death. Results: Among 133 cases of elderly AECOPD patients: the proportion of combined pulmonary heart disease and mechanical ventilation in death group was higher than that in survival group, PaCO2, WBC count, neutrophil count, NLR, CRP level in death group was higher, but lymphocyte count, serum albumin(ALB in death group was lower; multiple logistic regression analysis showed that NLR presented independent positive correlation with the in-hospital death in elderly AECOPD patients; ROC curve analysis showed that the ROCAUC of NLR to the inhospital death in elderly AECOPD patients was 0.787, the best diagnostic node value was 7.3, sensitivity and specificity were 77.4% and 74.5% respectively; bounded by NLR(7.3, divided patients into NLR≥7.3 group and NLR<7.3 group, hospital stays, CRP level and mortality in NLR≥7.3 group were higher than that in NLR<7.3 group. Conclusion: NLR was the high risk factor of the in-hospital death in elderly AECOPD patients, early detection of NLR level had a certain difference to the evaluation for short-term prognosis of elderly AECOPD patients and guide treatment.

Is total lymphocyte count related to nutritional markers in hospitalized older adults?

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Vânia Aparecida LEANDRO-MERHI

Full Text Available ABSTRACT BACKGROUND Older patients are commonly malnourished during hospital stay, and a high prevalence of malnutrition is found in hospitalized patients aged more than 65 years. OBJECTIVE To investigate whether total lymphocyte count is related to other nutritional markers in hospitalized older adults. METHODS Hospitalized older adults (N=131 were recruited for a cross-sectional study. Their nutritional status was assessed by the Nutritional Risk Screening (NRS, anthropometry, and total lymphocyte count. The statistical analyses included the chi-square test, Fisher's exact test, and Mann-Whitney test. Spearman's linear correlation coefficient determined whether total lymphocyte count was correlated with the nutritional markers. Multiple linear regression determined the parameters associated with lymphocyte count. The significance level was set at 5%. RESULTS According to the NRS, 41.2% of the patients were at nutritional risk, and 36% had mild or moderate depletion according to total lymphocyte count. Total lymphocyte count was weakly correlated with mid-upper arm circumference (r=0.20507; triceps skinfold thickness (r=0.29036, and length of hospital stay (r= -0.21518. Total lymphocyte count in different NRS categories differed significantly: older adults who were not at nutritional risk had higher mean and median total lymphocyte count ( P =0.0245. Multiple regression analysis showed that higher lymphocyte counts were associated with higher triceps skinfold thicknesses and no nutritional risk according to the NRS. CONCLUSION Total lymphocyte count was correlated with mid-upper arm circumference, triceps skinfold thickness, and nutritional risk according to the NRS. In multiple regression the combined factors that remained associated with lymphocyte count were NRS and triceps skinfold thickness. Therefore, total lymphocyte count may be considered a nutritional marker. Other studies should confirm these findings.

Clinical significance of the changes of distribution of peripheral blood lymphocyte subsets in patients after splenectomy for acute injury

International Nuclear Information System (INIS)

Zhou Guozhong

2005-01-01

Objective: To study the short-term effect of splenectomy on immuno-function as expressed by changes of peripheral lymphocyte subsets distribution in patients with acute injury. Methods: Peripheral blood lymphocyte subsets distribution types were studied with flow-cytometry in 74 patients before and 1 week after splenectomy for acute injury. Results: The percentage of CD 3 , CD 4 T cells were significantly higher (P 16-56 (NK), CD 19 B cells were significantly lower (P 8 T cell and CD 4 /CD 8 ratio were not significantly (P>0.05). Conclusion: There were significant changes of immunofunction right after splenectomy for acute injury, with enhancement of cellular immunofunction and depression of humoral immunofunction. (authors)

Activation of human T lymphocytes by Leishmania lipophosphoglycan

DEFF Research Database (Denmark)

Kemp, M; Theander, T G; Handman, E

1991-01-01

This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......, the results suggest that human T lymphocytes can respond to glycolipid antigens....

[The role of genetic polymorphisms of interleukins in chronic lymphocytic leukemia in patients of different ages].

Science.gov (United States)

Sirotina, S S; Tikunova, T S; Proshchaev, K I; Efremova, O A; Batlutskaia, I V; Iakunchenko, T I; Sobianin, F I; Churnosov, M I; Alekseev, S M

2014-01-01

Chronic lymphocytic leukemia (CLL) is a multifactorial disease, in which development the important role played the cytokine genes, in particular interleukins. This type of leukemia is more common in the elderly. The purpose of the study was to evaluate the association of genetic polymorphisms of interleukin with the development of chronic lymphocytic leukemia among residents of the Central Chernozem region of Russia. Genotyping of the -889C/T IL-1A, -590C/T IL-4 and VNTR IL-1 Ra was conducted in 206 patients with CLL and 307 individuals of the control group. The study found that the genetic risk factor for the development of CLL is allele -590T IL-4 (OR=-1,45). The development of thrombocytopenia in patients with CLL is associated with genetic variants -889T IL-1A (OR=1,95), -889TT IL-1A (OR=6,2) and IL-1Ra*1 (OR=-2,32).

Studies on the DNA excision repair in lymphocytes of patients with recurrent herpes simplex

International Nuclear Information System (INIS)

Fanta, D.; Topaloglou, A.; Altmann, H.

1979-01-01

DNA repair was investigated in lymphocytes from patients with recurrent herpes simplex and from healthy controls. From the results - depressed UV type repair, depressed gamma type repair, reduced RF - it may be concluded that mutations can be expected due to the faults remaining in the DNA. This may not only lower cellular immunocompetence, but also activate already present oncogenic virus informations within the cellular DNA. Thus, irrespective of the possible oncogenic potential of HSV, there seems to be an increased risk of late effects in patients with recurrent herpetic manifestations. (Auth.)

The aberrant asynchronous replication — characterizing lymphocytes of cancer patients — is erased following stem cell transplantation

International Nuclear Information System (INIS)

Nagler, Arnon; Cytron, Samuel; Mashevich, Maya; Korenstein-Ilan, Avital; Avivi, Lydia

2010-01-01

Aberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy levels in cells of patients with haematological malignancies from diagnosis to full remission, as achieved by allogeneic stem cell transplantation (alloSCT). TP53 (a tumor suppressor gene assigned to chromosome 17), AML1 (a gene assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 translocation) and the pericentomeric satellite sequence of chromosome 17 (CEN17) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosomes 17 and 21. Replication timing and aneuploidy were detected cytogenetically using fluorescence in situ hybridization (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes. We show that aberrant epigenetic markers are detected in patients with hematological malignancies from the time of diagnosis through to when they are scheduled to undergo alloSCT. These aberrations are unaffected by the clinical status of the disease and are displayed both during accelerated stages as well as in remission. Yet, these markers are eradicated completely following stem cell transplantation. In contrast, the increased levels of aneuploidy (irreversible genetic alterations) displayed in blood lymphocytes at various stages of disease are not eliminated following transplantation. However, they do not elevate and remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, applied in vitro to lymphocytes of patients prior to transplantation mimics the effect of transplantation: the epigenetic aberrations disappear while aneuploidy stays unchanged. The reversible nature of the replication aberrations may serve as potential epigenetic blood markers for evaluating

Sister chromatid exchange induced by X-irradiation of retinoblastoma lymphocytes

International Nuclear Information System (INIS)

Abramovsky-Kaplan, I.; Jones, I.S.

1984-01-01

Lymphocyte cultures were employed to assess the degree of spontaneous and induced chromosomal fragility in retinoblastoma. Sister chromatid exchange (SCEs) were scored in metaphases. Three unilateral, three bilateral, eleven family members and controls were studied. Retinoblastoma (RB) lymphocytes did not exhibit increased spontaneous fragility. X-irradiation (25-200 rad) did not significantly increase SCE in unilateral retinoblastoma lymphocytes when compared with controls (P greater than 0.50). However, bilaterally affected subjects and three unaffected relatives demonstrated a statistically significant increase in SCE (P less than 0.01). In conclusion, hereditary retinoblastoma lymphocytes appear more radiosensitive than sporadic retinoblastoma, perhaps, reflecting the increased second malignancies in germinal mutation retinoblastoma. In addition, the analysis of radiation-induced SCE in peripheral blood lymphocytes of RB patients and family members may provide a valuable tool increasing the accuracy of genetic counseling for this disorder. Additional studies of RB patients and families are needed to assess the relevance of this approach to genetic counseling

Assessment of individual radiosensitivity in human lymphocytes of cancer patients and its correlation with adverse side effects to radiation therapy

International Nuclear Information System (INIS)

Di Giorgio, Marina; Vallerga, Maria B.; Taja, Maria R.; Sardi, M.; Busto, E.; Roth, B.; Menendez, P.; Bonomi, M.; Mairal, L.

2003-01-01

Background and purpose: Individual radiosensitivity is an inherent characteristic, associated with an increased reaction to ionizing radiation on the human body. Biological endpoints such as clonogenic survival, chromosome aberration formation and repair capacity of radiation-induced damage have been applied to evaluate individual radiosensitivity in vitro. 5%-7% of cancer patients develop adverse side effects to radiation therapy in normal tissues within the treatment field, which are referred as 'clinical radiation reactions' and include acute effects, late effects and cancer induction. It has been hypothesized that the occurrence and severity of these reactions are mainly influenced by genetic susceptibility to radiation. Additionally, the nature of the genetic disorders associated with hypersensitivity to radiotherapy suggests that DNA repair mechanisms are involved. Consequently, the characterization of DNA repair in lymphocytes through cytokinesis blocked micronucleus (MN) and alkaline single-cell micro gel electrophoresis (comet) assays could be suitable approaches to evaluate individual radiosensitivity in vitro. The MN assay is an established cytogenetic technique to evaluate intrinsic cell radiosensitivity in tumor cells and lymphocytes; comet assay is a sensitive and rapid method for measuring DNA damage and repair in individual cells. The aims of this study were: 1) To assess the in vitro radiosensitivity of peripheral blood lymphocytes from two groups of cancer patients (retrospectively and prospectively studied), using MN and comet assays, in comparison with the observed clinical response; and 2) To test the predictive potential of both techniques. Materials and methods: 38 cancer patients receiving radiation therapy were enrolled in this study. The tumor sites were: head and neck (n 25) and cervix (n = 13). Nineteen patients were evaluated about 6-18 month after radiotherapy (retrospective group) and 19 patients were evaluated prior, mid-way and on

Effect of radiotherapy on the activity of lysosomal enzymes in lymphocytes and immunoglobulins in the serum in patients with laryngeal carcinoma

International Nuclear Information System (INIS)

Gierek, T.; Lisiewicz, J.; Kusnierczyk, W.; Plich, J.; Sasiadek, U.; Namyslowski, G.

1980-01-01

In 30 male patients aged 40 to 70 years treated with radiotherapy for laryngeal carcinoma presence of the lysosomal apparatus of the lymphocytes was observed after 6-9 years, with diffusion of the enzymes (especially beta-glucuronidase and N-acetyl-beta-glucosaminidase, and in a lower degree of acid phosphatase) from the lysosomes into the cytoplasm, and disappearance of normal lysosomal granules. The increased immunological reactivity of the patients was manifested frequently by a rise in the level of immunoglobulins, especially IgA in the serum, and a rise in the number of enzyme-positive lymphocytes (with the above-mentioned enzymes). (author)

Hypopituitarism possibly due to lymphocytic hypophysitis in a patient with type 1 diabetes.

Science.gov (United States)

Matoba, Keiichiro; Mitsuishi, Sumie; Hayashida, Satoshi; Yamazaki, Hiroyuki

2014-01-01

Hypopituitarism often develops insidiously, and undiagnosed hypopituitarism can influence the glycemic profile of patients with type 1 diabetes. We herein report the case of a 49-year-old man with type 1 diabetes and Hashimoto's thyroiditis who experienced an unexplained improvement in his glycemic level and recurrent severe hypoglycemia, despite a reduction in the dose of insulin. Based on the patient's endocrinological findings, he was diagnosed with hypopituitarism possibly due to lymphocytic hypophysitis, as supported by positive results for human leukocyte antigen A24 and Cw3. Following the administration of hydrocortisone replacement therapy, his insulin requirement increased to a premorbid level, and the severe hypoglycemia resolved.

Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

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Jiangdong Xiang

2017-02-01

Full Text Available PURPOSE: The monocyte-to-lymphocyte ratio (MLR has been shown to be associated with the prognosis of various solid tumors. This study sought to evaluate the important value of the MLR in ovarian cancer patients. METHODS: A total of 133 ovarian cancer patients and 43 normal controls were retrospectively reviewed. The patients' demographics were analyzed along with clinical and pathologic data. The counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR. and platelet-to-lymphocyte ratio (PLR. The optimal cutoff value of the MLR was determined by using receiver operating characteristic curve analysis. We compared the MLR, NLR, and PLR between ovarian cancer and normal control patients and among patients with different stages and different grades, as well as between patients with lymph node metastasis and non–lymph node metastasis. We then investigated the value of the MLR in predicting the stage, grade, and lymph node positivity by using logistic regression. The impact of the MLR on overall survival (OS was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Statistically significant differences in the MLR were observed between ovarian cancer patients and normal controls. However, no difference was found for the NLR and PLR. Highly significant differences in the MLR were found among patients with different stages (stage I-II and stage III-IV, grades (G1 and >G1, and lymph node metastasis status. The MLR was a significant and independent risk factor for lymph node metastasis, as determined by logistic regression. The optimal cutoff value of the MLR was 0.23. We also classified the data according to tumor markers (CA125, CA199, HE4, AFP, and CEA and conventional coagulation parameters (International Normalized Ratio [INR] and fibrinogen. Highly significant differences in CA125, CA199, HE4, INR, fibrinogen levels, and lactate

Radiosensitivity of peripheral blood lymphocytes in autoimmune disease

Energy Technology Data Exchange (ETDEWEB)

Harris, G [Kennedy Inst. of Rheumatology, London (UK). Div. of Experimental Pathology; Cramp, W A; Edwards, J C; George, A M; Sabovljev, S A; Hart, L; Hughes, G R.V. [Hammersmith Hospital, London (UK); Denman, A M [Northwich Park Hospital, Harrow (UK); Yatvin, M B [Wisconsin Clinical Cancer Center, Madison (USA)

1985-06-01

The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease.

Cytogenetic radiosensitivity of G0-lymphocytes of breast and esophageal cancer patients as determined by micronucleus assay

International Nuclear Information System (INIS)

Mozdarani, H.; Mansouri, Z.; Haeri, S.A.

2005-01-01

Enhanced chromosomal radiosensitivity is a feature of many cancer predisposition conditions, indicative of the important role of chromosomal alterations in carcinogenesis. In this study the cytokinesis-blocked micronucleous assay was used to compare the radiosensitivity of blood lymphocytes obtained from Iranian breast or esophageal cancer patients (n=50, n=16; respectively) with that of control individuals (n=40). For each sample, one thousand binucleate lymphocytes were analyzed before and after in vitro exposure to 3 Gy of γ rays. The radiation-induced frequency of micronucleus was significantly higher in the breast cancer group (261/1,000 binucleated cells) than in esophageal cancer group (241/1,000 binucleated cells, P<0.01) or in the control group (240/1,000 binucleated cells, P<0.01). The results indicate that breast cancer patients are more radiosensitive compared to normal healthy individuals or esophageal cancer patients. Increased radiosensitivity could be due to defects in DNA repair genes involved in breast cancer formation. Since patients with esophageal cancer did not show elevated radiosensitivity, it is assumed that the contribution of radiosensitivity-related genes to the development of esophageal cancer may be smaller than the contribution of those genes to breast cancer. (author)

An Alteration of Lymphocytes Subpopulations and Immunoglobulins Levels in Patients with Diabetic Foot Ulcers Infected Particularly by Resistant Pathogens

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Vladimíra Fejfarová

2016-01-01

Full Text Available The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs especially those infected by resistant microorganisms. Methods. 68 patients treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n=50 and subgroup R by resistant pathogens (n=18. Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p<0.01 and total numbers of lymphocytes (p<0.001 involving B lymphocytes (p<0.01, CD4+ (p<0.01, and CD8+ T cells (p<0.01 and their naive and memory effector cells. Higher levels of IgG (p<0.05 including IgG1 (p<0.001 and IgG3 (p<0.05 were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p<0.05. A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS. Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p<0.01 in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls.

Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are associated with chronic hepatitis B virus (HBV) infection.

Science.gov (United States)

Zhao, Zhidan; Liu, Jianhua; Wang, Jiaxin; Xie, Tinyan; Zhang, Qiuhuan; Feng, Sisi; Deng, Hui; Zhong, Baiyun

2017-10-01

This retrospective study aimed to investigate the associations between the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and disease severity in patients with chronic HBV infection-related liver disease (CHB). Patients with CHB were retrospectively identified. Clinical data for 172 HBV-infected patients and 40 healthy controls were collected from the electronic patient medical record system database of our hospital. HBV-related-compensated-cirrhosis patients (HBV-CC patients) had a significantly lower mean PLR than did other patients (PHBV-related-decompensated-cirrhosis patients (HBV-DC patients) had a significantly higher mean NLR than did any other patients (PHBV DNA (r=0.264, PHBV DNA in both HBV-CC patients (r=-0.116, P=0.044) and HBV-DC patients (r=0.456, P=0.008). In HBV-Active-Carriers patients (HBV-AC patients), the PLR was positively correlated with serum HBeAg level (r=0.321, P=0.023). In HBV-DC patients, the NLR was positively correlated with serum HBeAg level (r=0.372, P=0.033). In the logistic regression prediction model, a predictive probability cutoff of 0.392 had the highest sensitivity and specificity (sensitivity, 91.2%; specificity, 84.0%) in distinguishing between HBV-CC and HBV-AC patients. A NLR cutoff value of 2.94 had the highest sensitivity and specificity (sensitivity, 81.8%; specificity, 88.2%) in distinguishing between HBV-DC and HBV-CC patients. The PLR and NLR partially reflect the amounts of serum HBV DNA and serum HBeAg levels circulating in CHB patients. The logistic regression model including the PLR and age most accurately distinguished between HBV-CC and HBV-AC patients. The NLR may be useful for follow-up in HBV-CC patients to predict disease progression. In summary, the PLR and NLR provided a supplementary means for effectively managing chronic HBV infection and disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Individual radiosensitivity does not correlate with radiation-induced apoptosis in lymphoblastoid cell lines or CD{sup 3+} lymphocytes

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Wistop, A.; Keller, U.; Grabenbauer, G.G.; Sauer, R.; Distel, L.V.R. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg, Erlangen (Germany); Sprung, C.N. [Div. of Research, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia)

2005-05-01

Background and purpose: spontaneous and radiation-induced apoptosis of lymphoblastoid cell lines (LCLs) derived from healthy donors, cancer patients and donors with radiosensitivity syndromes as well as CD{sup 3+} lymphocytes from patients with {>=} grade 3 late toxicity were investigated as a possible marker for the detection of individual radiosensitivity. These investigations are based on the hypothesis that hypersensitive patients have reduced levels of apoptosis after in vitro irradiation as a result of a defect in the signaling pathway. Material and methods: Epstein-Barr virus-(EBV-)transformed LCLs derived from five healthy donors, seven patients with heterozygous or homozygous genotype for ataxia-telangiectasia or Nijmegen breakage syndrome and five patients with {>=} grade 3 late toxicity (RTOG) were investigated. In addition, CD{sup 3+} lymphocytes from 21 healthy individuals and 18 cancer patients including five patients with a proven cellular hypersensitivity to radiation were analyzed. Cells were irradiated in vitro with a dose of 2 and 5 Gy and were incubated for 48 h. Apoptotic rates were measured by the TUNEL assay followed by customized image analysis. Results: four out of seven radiosensitivity syndrome patients were identified to have an increased cellular radiosensitivity as determined by reduced apoptotic rates after irradiation of their respective LCLs. Comparatively, only two of the five hypersensitive cancer patients were clearly identified by reduced apoptotic rates. Spontaneous apoptotic rates were very homogeneous among all 39 samples from controls and patients, while lymphocytes of all cancer patients showed significantly lower radiation-induced rates. Conclusion: only a subgroup of hypersensitive patients may be identified by reduction of radiation-induced apoptotic rate. It is concluded that the hypothesis according to which hypersensitive cells have reduced levels of apoptosis is only conditionally true. The authors suggest that this

Chlorambucil for the treatment of patients with chronic lymphocytic leukemia (CLL) - a systematic review and meta-analysis of randomized trials.

Science.gov (United States)

Vidal, Liat; Gurion, Ronit; Ram, Ron; Raanani, Pia; Bairey, Osnat; Robak, Tadeusz; Gafter-Gvili, Anat; Shpilberg, Ofer

2016-09-01

Randomized clinical trials that compared chlorambucil to different regimens, for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) do not support an overall survival (OS) benefit. To assess the efficacy and safety of chlorambucil as frontline treatment, we conducted a systematic review and meta-analysis of randomized controlled trials. OS was the primary outcome. Meta-analysis of 18 trials that compared purine analogs, alkylators, alemtuzumab and ibrutinib to chlorambucil demonstrated no OS benefit for therapy without chlorambucil over chlorambucil (pooled HR 0.99, 95% CI 0.91-1.08; 4133 patients). PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection. The risk of secondary malignancies was not increased with chlorambucil. In conclusion, our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL. Purine analogs should be preferred in fit younger patients because of longer PFS. Future trials should focus on unfit patients who are underrepresented in clinical trials.

Correlation between Lymphocyte CD4 Count, Treatment Duration, Opportunistic Infection and Cognitive Function in Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS) Patients.

Science.gov (United States)

Fitri, Fasihah Irfani; Rambe, Aldy Safruddin; Fitri, Aida

2018-04-15

Human immunodeficiency virus (HIV) infection is an epidemic worldwide, despite the marked benefits of antiretroviral therapy (ARV) in reducing severe HIV-associated dementia. A milder form of neurocognitive disorders are still prevalent and remain a challenge. This study aimed to determine the correlation between plasma cluster of differentiation 4 (CD4) lymphocyte, duration of ARV treatment, opportunistic infections, and cognitive function in HIV-AIDS patients. A cross-sectional study involving 85 HIV-AIDS patients was conducted at Adam Malik General Hospital Medan, Indonesia. All subjects were subjected to physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts. Out of the 85 subjects evaluated, the proportion concerning sexes include 52 males (61.2 %) and 33 females (38.8%). The mean age was 38.53 ± 9.77 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r = 0.271, p = 0.012), but there was no significant correlation between duration of ARV treatment and MoCA-INA score. There was also no difference in MoCA-INA score based on the presence of opportunistic infection. Lymphocyte CD4 count was independently correlated with cognitive function in HIV-AIDS patients.

Prediction of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma by Using Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio.

Science.gov (United States)

Ozgonul, Cem; Sertoglu, Erdim; Mumcuoglu, Tarkan; Ozge, Gokhan; Gokce, Gokcen

2016-12-01

To assess the levels of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with pseudoexfoliation syndrome (PEX) and to compare the NLR and PLR results of patients with PEX, PEX glaucoma (PXG), and healthy controls. In total, 34 patients with PEX, 29 patients with PXG, and 42 healthy subjects were enrolled in this retrospective study. Complete ophthalmologic examination and complete blood count measurements were performed of all subjects. Complete blood counts were performed within 2 h of blood collection. There was a significant difference in NLR between PEX and control groups (p = 0.012) and PXG and control groups (p = 0.003). Also, a significant difference was found in PLR values between control and PXG groups (p = 0.024). Our study for the first time provides evidence that PLR and NLR may be useful for predicting the prognosis of PEX patients and progression to PXG.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

Science.gov (United States)

Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulbegović, Nedžad

2014-05-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

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Maida Rakanović-Todić

2014-05-01

Full Text Available Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS. The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL. However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted. 

Investigations on the influence of radiotherapy on the extent of DNA-repair in peripheral lymphocytes and tumor cells of patients with cancer

International Nuclear Information System (INIS)

Klein, W.; Koren, H.; Alth, G.; Klein, H.

1977-02-01

The influence of radiotherapy on DNA excision repair after setting UV-lesions in peripheral lymphocytes and tumor cells of 11 patients with different forms of cancer was investigated. The effect of short term radiotherapy was compared with that after irradiation over a longer period. Radiotherapy provoked inhibition of DNA repair in tumor cells in every case, whereas changes in lymphocytes were dependent on irradiation schedule. (author)

Chronic Lymphocytic Leukemia: Current Concepts.

Science.gov (United States)

Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

2015-10-01

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Beta-adrenergic receptors of lymphocytes in children with allergic respiratory diseases

International Nuclear Information System (INIS)

Bittera, I.; Gyurkovits, K.; Falkay, G.; Eck, E.; Koltai, M.

1988-01-01

The beta-adrenergic receptor binding sites on peripheral lymphocytes in children with bronchial asthma (n = 16) and seasonal allergic rhinitis (n = 8) were examined in comparison with normal controls (n = 18) by means of 124 I-cyanopindolol. The number of beta-adrenergic receptors was significantly lower in the asthmatic group (858 +/- 460/lymphocyte) than in the controls (1564 +/- 983/lymphocyte). The value (1891 +/- 1502/lymphocyte in children with allergic rhinitis was slightly higher than that in healthy controls. Of the 24 patients suffering from allergic diseases of the lower or upper airways, the bronchial histamine provocation test was performed in 21; 16 gave positive results, while 5 were negative. No difference in beta-adrenergic receptor count was found between the histamine-positive and negative patients. Neither was there any correlation between the number of beta-adrenergic receptors and the high (16/24) and low (8/24) serum IgE concentrations found in allergic patients. The significant decrease in beta-adrenergic receptor count in asthmatic children lends support to Szentivanyi's concept. Further qualitative and quantitative analysis of lymphocyte beta-adrenergic receptors may provide an individual approach to the treatment of bronchial asthma with beta-sympathomimetic drugs

Radiation effects on lymphocytes

International Nuclear Information System (INIS)

Roser, B.

1976-01-01

This review of the ontogeny of lymphocyte populations concentrates on sites of production, rates of production, and the factors governing the differentiation and longevity of the various lymphocyte pools. The physiology of the lymphocyte pools is described with particular emphasis on recirculation from blood to lymph through lymphoid tissues. The separate routes of recirculation of both thymus-derived and nonthymus-derived lymphocytes and the possible anatomical sites and mechanisms of lymphocyte cooperation are discussed. Radiation effects on lymphocyte populations are divided into two sections. First, the effects of whole-body irradiation on the total lymphocyte pools are discussed including the differential effects of irradiation on T lymphocytes, B lymphocytes, lymphoblasts, and plasma cells. The differential sensitivity of various types of immune response is correlated, where possible, with the differential sensitivity of the lymphocyte types involved. Second, experimental attempts to selectively deplete discrete subpopulations of the total lymphocyte pools, e.g., recirculating cells, are briefly discussed with particular emphasis on studies on the effects of the localization of radionuclides in lymphoid tissue

Cellular immune therapy for chronic lymphocytic leukemia

NARCIS (Netherlands)

Kater, Arnon P.; van Oers, Marinus H. J.; Kipps, Thomas J.

2007-01-01

Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for

Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro

International Nuclear Information System (INIS)

Kawasaki, E.S.; Clark, S.S.; Coyne, M.Y.; Smith, S.D.; Champlin, R.; Witte, O.N.; McCormick, F.P.

1988-01-01

The Philadelphia chromosome is present in more than 95% of chronic myeloid leukemia patients and 13% of acute lymphocytic leukemia patients. The Philadelphia translocation, t(9;22), fuses the BCR and ABL genes resulting in the expression of leukemia-specific, chimeric BCR-ABL messenger RNAs. To facilitate diagnosis of these leukemias, the authors have developed a method of amplifying and detecting only the unique mRNA sequences, using an extension of the polymerase chain reaction technique. Diagnosis of chronic myeloid and acute lymphocytic leukemias by this procedure is rapid, much more sensitive than existing protocols, and independent of the presence or absence of an identifiable Philadelphia chromosome

The effects of low dose radiation (LDR) on lymphocytes

International Nuclear Information System (INIS)

Su Liaoyuan; Du Zeji; Tian Hailin; Zhao Yujie; Zou Huawei; Zhou Jianhua; Kong Xiangrong; Zhang Jianhua; Shen Wei

2001-01-01

LDR could stimulate lymphocyte transformation for adults, children and infants. The effect of LDR on lymphocytes in malnourished children was lower, but higher on lymphocytes in cord blood. The effect of LDR on CD 4 + cells in adult persons was higher than that on CD + cells. NK cells were radioresistant. The stimulative effect of LDR on NK activity in tumor patients was lower than that in normal individuals. For the mice with tumors, LDR could increase the ratio of L 3 T 4 cells in blood, spleen and the number of cytotoxic T cells in the tumors. Extracellular fluid of the lymphocytes operated by LDR could also stimulate the lymphocyte transformation. The preliminary LDR could decrease the injuries to macromolecules, membrane antigens and chromosomes in lymphocytes which were induced by high dose radiation. The LDR- induced protein might be found from mouse spleen cells, and this protein could increase immune function in human and animals

Unstable chromosome aberrations on peripheral blood lymphocytes from patients with cervical uterine cancer following radiotherapy

International Nuclear Information System (INIS)

Magnata, Simey de Souza Leao Pereira

2002-09-01

Absorbed dose determination is an important step for risk assessment related to an exposure to ionizing radiation. However, physical dosimetry cannot be always performed, principally in the case of retrospective estimates. In this context, the use of bioindicators (biological effects) has been proposed, which defines the so-called biological dosimetry. In particular, scoring of unstable chromosomes aberrations (dicentrics, centric rings and fragments) of peripheral blood lymphocytes, while is the most reliable biological method for estimating individual exposure to ionizing radiation. In this work, blood samples from 5 patients, with cervical uterine cancer, were evaluated after partial-body radiotherapy with a source of 69 Co. For this, conventional cytogenetic method was employed, based on Giemsa coloration and fluorescence in situ hybridization, in order to correlate the frequency of unstable chromosome aberrations of blood lymphocytes with absorbed dose, as a result of the radiotherapy. A good agreement was observed between the frequency of chromosome aberrations scored and the values of dose previously calculated by physical dosimetry during patient's radiotherapy. The results presented in this work point out the importance of concerning analyses of unstable chromosome aberrations as biological dosimeter in the investigation of partial-body exposure to ionizing radiation. (author)

The absence of radiation-induced adaptive response in lymphocytes of patients with Down's syndrome

International Nuclear Information System (INIS)

Khandogina, E.K.; Mutovin, G.R.; Zvereva, S.V.; Zverev, D.O.; Neudakhin, E.V.; Arkhipov, B.A.; Akif'ev, A.P.; AN SSSR, Moscow

1991-01-01

The adaptive syndrome and response (AR) in lymphocytes from 6 patients with Down syndrome (DS) were investigated. No AR was found to occur in all cases in DS cells pre-exposed to 3 rad of X-rays in S phase of cell cycle and then irradiated with 150 rad of gamma rays in G2 whereas the chromosome aberrations yield in cells from control donors was decreased twice under such conditions of the experiment

Increased 22Na+-influx in lymphocytes from offspring of essential hypertensive patients

DEFF Research Database (Denmark)

Nielsen, J R; Pedersen, K E; Klitgaard, N A

1989-01-01

Lymphocytes were used as a cellular model for the in vitro measurements of 22Na+-influx during sodium pump inhibition by ouabain. The measurements were made using lymphocytes from young men at increased risk of developing essential hypertension in order to assess any changes and to analyse whether...

Chemokines, lymphocytes, and HIV

Directory of Open Access Journals (Sweden)

Farber J.M.

1998-01-01

Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: A prospective study

International Nuclear Information System (INIS)

Ammenheuser, M.M.; Au, W.W.; Whorton, E.B. Jr.; Belli, J.A.; Ward, J.B. Jr.

1991-01-01

The autoradiographic 6-thioguanine-resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time-course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x-irradiation therapy. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m 2 of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post-treatment sample times. The results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times

Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

Science.gov (United States)

Pasricha, Sarina; Gupta, Amit; Reed, Craig C; Speck, Olga; Woosley, John T; Dellon, Evan S

2016-10-01

Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

Lymphocytic Esophagitis: An emerging clinicopathologic disease associated with dysphagia

Science.gov (United States)

Pasricha, Sarina; Gupta, Amit; Reed, Craig C.; Speck, Olga; Woosley, John T.; Dellon, Evan S.

2016-01-01

Background Lymphocytic Esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. Aim To characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. Methods We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000 and June 1, 2012. Archived pathology slides were re-reviewed and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Results 27 adults were diagnosed with LyE, and the majority were female (63%). The most common symptom was dysphagia (70%). 52% had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37%), erosive esophagitis (33%), rings (26%), and hiatal hernia (26%); 33% of patients required dilation. After histology re-review, 78% of LyE patients were found to have more than 20 lymphs/hpf. In comparison to the normal, reflux and EoE controls, patients with LyE tended to be non-white (pdysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. PMID:27343035

GENETIC POLYMORPHISM AND CYTOGENETIC CHANGES IN THE PERIPHERAL BLOOD T-LYMPHOCYTES OF PATIENTS WITH ARTHRITIS ASSOCIATED WITH IXODES TICK-BORNE BORRELIOSIS IN THE NORTHERN REGIONS OF SIBERIA

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N. N. Ilyinskikh

2017-01-01

Full Text Available The authors have previously conducted studies that demonstrate the increased level of cytogenetic disturbances in patients with Ixodes tick-borne borreliosis (ITB. The severity of arthritis associated with ITB (AITB is also ascertained to depend on whether the patient has certain HLA-DRB1 alleles.Objective: to assess the association between HLA-DRB1 gene polymorphism and cytogenetic changes in the peripheral blood T lymphocytes of patients with AITB.Subjects and methods. 146 patients with AITB, 100 clinically healthy convalescents with ITB (CITB, and a control group of 98 healthy blood donors (HBDs without a history of tick-borne infections were examined using cytogenetic (micronucleus analysis of cytokinesis-blocked peripheral blood T lymphocytes and molecular genetic (PCR analysis of HLA-DRB1 gene polymorphism methods.Results and discussion. The frequency of cytokinesis-blocked lymphocytes with micronuclei in the AITB group was significantly higher than that in the CITB and HBD groups (p<0.01 with the exception of the results obtained in the subgroup of patients with AITB who had the DRB1*10 allele (p>0.05. The highest levels of lymphocytes with micronuclei were observed in AITB patients with the DRB1*17(03, *01, and *04 alleles as compared to those in the CITB and HBD groups (p<0.001. The CITB group showed the most significant increase in the detection rate of lymphocytes with micronuclei in people with the DRB1*01, DRB1*04, or *17(03 alleles. At the same time, there were no significant differences in the number of lymphocytes with micronuclei in the HBD group, depending on the HLA-DRB1 gene alleles (p>0.05. Thus, the patients with AITB had the highest frequency of cytogenetic disorders with the exception of individuals with the DRB1*10 allele.

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders

International Nuclear Information System (INIS)

Reddy, E.P.; Mettus, R.V.; DeFreitas, E.; Wroblewska, Z.; Cisco, M.; Koprowski, H.

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, the authors have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. They have clones the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome

The Coexistence of an Intrasellar Adenoma, Lymphocytic Hypophysitis, and Primary Pituitary Lymphoma in a Patient with Acromegaly

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Jose Hernan Martinez

2011-01-01

Full Text Available The concomitant presence of three histopathologically different entities in the pituitary gland is a rare occurrence. Most publications identify at least two distinct pathologies, mainly, a pituitary adenoma coexisting with a second intrasellar lesion. We present a case of a 71-year-old female referred for evaluation and treatment of acromegaly. Questioning revealed she was experiencing facial palsy, visual disturbances, and syncopal spells for several weeks. When laboratory evaluation showed elevated somatomedin (IGF-I levels and an oral glucose tolerance test failed to demonstrate any suppression of her growth hormone (GH values, an MRI of the pituitary revealed a sellar mass. A presumptive diagnosis of pituitary adenoma was established. The patient underwent transsphenoidal resection of the sellar mass, which proved to be a large B-cell lymphoma (Stage I-E associated with areas of adenoma and lymphocytic hypophysitis.

The role of stem cell mobilization regimen on lymphocyte collection yield in patients with multiple myeloma.

Science.gov (United States)

Hiwase, D K; Hiwase, S; Bailey, M; Bollard, G; Schwarer, A P

2008-01-01

The lymphocyte dose (LY-DO) infused during an autograft influences absolute lymphocyte (ALC) recovery and survival following autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Factors influencing lymphocyte yield (LY-C) during leukapheresis have been poorly studied. Factors that could influence survival, LY-C and CD34(+) cell yield were analyzed in 122 MM patients. Three mobilization regimens were used, granulocyte-colony-stimulating factor (G-CSF) alone (n=13), cyclophosphamide 1-2 g/m(2) plus G-CSF (LD-CY, n=62) and cyclophosphamide 3-4 g/m(2) and G-CSF (ID-CY, n=47). Using multivariate analysis, age, LY-C, ALC on day 30 (ALC-30) and International Staging System stage significantly influenced overall (OS) and progression-free survival (PFS) following ASCT. PFS (56 versus 29 months, P=0.05) and OS (72 versus 49 months; P=0.07) were longer in the LY-C>or=0.12x10(9)/kg group than the LY-Cradiotherapy and number of leukaphereses significantly influenced LY-C. Significantly higher LY-C was obtained with G-CSF alone compared with the LD-CY and ID-CY groups. CD34(+) count on the day of leukapheresis, prior chemotherapy with prednisone, cyclophosphamide, adriamycin and BCNU or melphalan, and stem cell mobilization regimen significantly influenced CD34(+) cell yield. LY-C influenced ALC-15 and survival following ASCT. Factors that influenced CD34(+) cell yield and LY-C during leukapheresis were different. Mobilization should be tailored to maximize the LY-C and CD34(+) cell yield.

Chromosome radiosensitivity and kinetics of proliferation of peripheral lymphocytes in individuals with aneuploid karyotype

Energy Technology Data Exchange (ETDEWEB)

Konecna, H; Kalina, I; Ondrussekova, A

1988-08-01

Experimentally investigated was the radiosensitivity of chromosomes and the kinetics of the proliferation of peripheral lymphocytes in patients with aneuploid (DS and TS) and normal karyotype irradiated in vitro in the G/sub o/ stage of the cell cycle. Trisomic lymphocytes were found to proliferate more rapidly in the in vitro culture and to be more sensitive than diploid cell populations. In monosomic lymphocytes in Turner syndrome patients, the proliferation and incidence of chromosomal abberations was similar to the disomic lines in Down's syndrome patients and in Turner syndrome patients, and to that found in persons with a normal karyotype. The results of the experiment show that there is a relationship between the proliferation rate of peripheral lymphocytes cultures in vitro and the radiosensivity of chromosomes. (author). 1 tab., 3 figs., 11 refs.

Chromosome radiosensitivity and kinetics of proliferation of peripheral lymphocytes in individuals with aneuploid karyotype

International Nuclear Information System (INIS)

Konecna, H.; Kalina, I.; Ondrussekova, A.

1988-01-01

Experimentally investigated was the radiosensitivity of chromosomes and the kinetics of the proliferation of peripheral lymphocytes in patients with aneuploid (DS and TS) and normal karyotype irradiated in vitro in the G o stage of the cell cycle. Trisomic lymphocytes were found to proliferate more rapidly in the in vitro culture and to be more sensitive than diploid cell populations. In monosomic lymphocytes in Turner syndrome patients, the proliferation and incidence of chromosomal abberations was similar to the disomic lines in Down's syndrome patients and in Turner syndrome patients, and to that found in persons with a normal karyotype. The results of the experiment show that there is a relationship between the proliferation rate of peripheral lymphocytes cultures in vitro and the radiosensivity of chromosomes. (author). 1 tab., 3 figs., 11 refs

JAK2V617F mutation in a patient with B-cell chronic lymphocytic leukemia and prefibrotic primary myelofibrosis

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Ristić Slobodan

2015-01-01

Full Text Available Introduction. Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL, but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. Case Outline. We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL who developed primary myelofibrosis (PMF nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. Conclusion. Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell. [Projekat Ministarstva nauke Republike Srbije, br. III 41004

Lymphocytic Arteritis in Epstein-Barr Virus Vulvar Ulceration (Lipschütz Disease): A Report of 7 Cases.

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Barrett, Mary M; Sangüeza, Martin; Werner, Betina; Kutzner, Heinz; Carlson, John A

2015-09-01

Epstein-Barr virus (EBV) infection can rarely present as painful genital ulcers, mostly in young female adolescents. Typically diagnosed by clinical findings, EBV vulvar ulceration (EBVVU) is rarely biopsied. Herein, the authors report the histopathology in 8 biopsies from 7 EBVVU patients, all serologically confirmed for acute (4/7) or reactivated-chronic (3/7) EBV infection. The 7 women all presented with 1 or more painful, punched-out vulvar ulcers. Only patients with acute EBV infection showed other clinical findings: fever and/or atypical lymphocytosis affected 75% (3/4); lymphadenopathy in 50%; and malaise/fatigue, dysuria and/or hepatomegaly in 25%. All reactivated-chronic EBVVU had a solitary ulcer, and 2 had history of a similar episode of vulvar ulceration (aphthosis). Histopathologically, lymphocytic arteritis was identified in 88% (7/8); a submucosal scar was found in the eighth specimen. Other histopathologies included venulitis (62%), endarteritis obliterans (38%), thrombosis (25%), neutrophilic sebaceous adenitis (25%), and mucosal lymphoid hyperplasia (12%). Dense angiocentric CD3 CD4 T-cell lymphocyte-predominant infiltrates were found, regionally or diffusely. In 2 specimens, neutrophils compromised half of the infiltrate. Minor components of CD8, CD20, and CD30 lymphocytes, CD123 plasmacytoid monocytes, CD68 macrophages, and plasma cells were present. Small-vessel endothelium and smooth muscle adjacent to the ulcers faintly expressed cytoplasmic EBV latent membrane protein-1 (LMP1). In situ hybridization for early EBV mRNA (EBER) identified rare solitary or scattered clustered positive lymphocytes in 38%. Polymerase chain reaction for EBV DNA was positive in one EBER positive biopsy. EBV infection has been documented in muscular vessel vasculitis. Based on the aforementioned, EBVVU appears to be the consequence of localized lymphocytic arteritis.

Definite vs adjuvant radiotherapy. Comparative effects on lymphocyte subpopulations in patients with head and neck squamous carcinoma

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Wolf, G.T.; Amendola, B.E.; Diaz, R.; Lovett, E.J. III; Hammerschmidt, R.M.; Peterson, K.A.

1985-01-01

The recent association of alterations in T-lymphocyte subpopulations and impaired cellular immunity prompted an investigation of the effects of radiotherapy (RT) on serial levels of lymphocyte subsets in 30 patients with head and neck squamous carcinoma. Percentage and absolute levels of T3, T4, T6, T8, T10, T11, and Leu 7 cells were measured before, during, and after RT at monthly intervals for six months and compared with levels in 40 normal subjects. Sixteen patients received curative and 14 postoperative adjuvant RT. Before treatment, mean subset levels were similar among the patient and normal groups except for elevated Leu 7 (natural killer) cells in patients with stage I and II disease. There were profound decreases in absolute levels of each subpopulation during and after RT. The percentage of T4 (helper/inducer) cells decreased, whereas that of T8 (cytotoxic/suppressor) and Leu 7 cells tended to increase. Compared with normal values, the mean T4/T8 ratio decreased significantly by six months after RT, when absolute levels of the subsets had rebounded to pretreatment levels in the definitive RT group but remained profoundly decreased in the adjuvant group. The differing recovery patterns suggest that factors other than RT may contribute to persistent immunosuppression following RT

Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

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Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

2015-07-01

Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Lymphocyte receptors for pertussis toxin

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Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

1990-12-01

We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation

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Martin, C.; Romero, S.; Arriero, J.M.; Hernandez, L.; Sanchez-Paya, J.; Massuti, B.

1999-01-01

The main aim of the present study was to assess the early diagnostic value of bronchoalveolar lavage (BAL) in radiation-induced lung injury in patients with breast carcinoma. Twenty-six females receiving postoperative radiotherapy for breast cancer were evaluated before and 0, 15, 30, 60 , and 180 days after radiotherapy. History, physical examination, chest radiographs, and pulmonary function tests were obtained. BAL, including lymphocyte subsets analysis, was limited to the second evaluation after radiotherapy. A group of 21 healthy females were used as control. Findings after radiotherapy in asymptomatic patients were compared with findings in a group of patients with radiation pneumonitis. Irradiated patients showed a significantly (p<0.01) greater percentage (29.5±15.7%) of BAL lymphocytes than controls (6.2±3.3%). No statistical differences existed in BAL findings between the irradiated and unirradiated sides of the chest. Percentages of BAL lymphocytes did not differ significantly between patients who developed subsequent pneumonitis (24.5±13.5%) and those who did not develop pneumonitis (32.8±16.5%). Patients with pneumonitis at the time of BAL had significantly higher (p<0.05) alveolar CD4 subset cells (24.8±10.2%) than asymptomatic patients (15.2±8.9%). Maximal reductions in total lung capacity (p<0.01), and residual volume (p<0.05) occurred 60 days after irradiation. The early lymphocytic alveolitis induced by unilateral thoracic radiotherapy in most patients with breast cancer is always bilateral and does not predict the subsequent development of radiological evidence of pneumonitis. (au)

Bilateral lymphocytic alveolitis: a common reaction after unilateral thoracic irradiation

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Martin, C.; Romero, S.; Arriero, J.M.; Hernandez, L. [Hospital General Universitario, Servicios de Neumologia, Alicante (Spain); Sanchez-Paya, J. [Hospital General Universitario, Epidemiologia, Alicante (Spain); Massuti, B. [Hospital General Universitario, Oncologia, Alicante (Spain)

1999-04-01

The main aim of the present study was to assess the early diagnostic value of bronchoalveolar lavage (BAL) in radiation-induced lung injury in patients with breast carcinoma. Twenty-six females receiving postoperative radiotherapy for breast cancer were evaluated before and 0, 15, 30, 60 , and 180 days after radiotherapy. History, physical examination, chest radiographs, and pulmonary function tests were obtained. BAL, including lymphocyte subsets analysis, was limited to the second evaluation after radiotherapy. A group of 21 healthy females were used as control. Findings after radiotherapy in asymptomatic patients were compared with findings in a group of patients with radiation pneumonitis. Irradiated patients showed a significantly (p<0.01) greater percentage (29.5{+-}15.7%) of BAL lymphocytes than controls (6.2{+-}3.3%). No statistical differences existed in BAL findings between the irradiated and unirradiated sides of the chest. Percentages of BAL lymphocytes did not differ significantly between patients who developed subsequent pneumonitis (24.5{+-}13.5%) and those who did not develop pneumonitis (32.8{+-}16.5%). Patients with pneumonitis at the time of BAL had significantly higher (p<0.05) alveolar CD4 subset cells (24.8{+-}10.2%) than asymptomatic patients (15.2{+-}8.9%). Maximal reductions in total lung capacity (p<0.01), and residual volume (p<0.05) occurred 60 days after irradiation. The early lymphocytic alveolitis induced by unilateral thoracic radiotherapy in most patients with breast cancer is always bilateral and does not predict the subsequent development of radiological evidence of pneumonitis. (au) 38 refs.

Occurrence of chronic lymphocytic leukemia in patients with chronic myelogenous leukemia

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Pritish K Bhattacharyya

2013-01-01

Full Text Available Chronic lymphocytic leukemia (CLL is the most common leukemia of adults in the western world and constitutes about 33% of all leukemia′s. The incidence of CLL increases with age and are more common in older population. Chronic myeloid leukemia (CML on the contrary occurs in both young adults and elderly and is a chronic myeloproliferative disease that originates from abnormal pluripotent stem cells and results in involvement of multiple hematopoietic lineages, but predominantly myeloid and less commonly lymphoid. Association between CLL and myeloid malignancies (CML, acute myeloid leukemia and MDS, myelodysplastic syndrome is rare. In literature documenting CLL and CML in same patients, occur either simultaneously or CML is preceded by CLL.

Neutrophil-to-Lymphocyte Ratio as a Marker in Patients with Non-arteritic Anterior Ischemic Optic Neuropathy

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Onur Polat

2015-12-01

Full Text Available Background: Non-arteritic anterior ischemic optic neuropathy (NAION is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Although the precise cause of NAION remains elusive, the etiology of NAION is believed to be multifactorial. Aims: To evaluate the utility of neutrophil-to-lymphocyte ratio (NLR as a simple and readily available prognostic factor for clinical disease activity in patients with NAION. Study Design: Case-control study. Methods: Forty-five patients with the diagnosis of NAION and 50 age- and sex-matched controls with/without any systemic or ocular diseases except cataract were retrospectively enrolled in the study. Demographic characteristics and laboratory findings including complete blood count of all patients and control subjects were obtained from the electronic medical record. The neutrophil and lymphocyte counts were recorded and the NLR was calculated. Results: White blood cell, neutrophil, NLR and platelet values of the NAION patients were significantly higher than those of the controls (p<0.001, p<0.001, p=0.004, p=0.037, respectively. Initial NLR values were negatively correlated with initial and the third month best corrected visual acuity levels in the study group. The optimum NLR cut-off point for NAION was 1.94. Conclusion: NLR could be considered as a new inflammatory marker for assessment of the severity of inflammation in NAION patients with its quick, cheap, easily measurable property with routine complete blood count analysis.

Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions

International Nuclear Information System (INIS)

Hartel, Carola; Nikoghosyan, Anna; Durante, Marco; Sommer, Sylwester; Nasonova, Elena; Fournier, Claudia; Lee, Ryonfa; Debus, Juergen; Schulz-Ertner, Daniela; Ritter, Sylvia

2010-01-01

Background and purpose: To investigate the cytogenetic damage in blood lymphocytes of patients treated for prostate cancer with different radiation qualities and target volumes. Materials and methods: Twenty patients receiving carbon-ion boost irradiation followed by IMRT or IMRT alone for the treatment of prostate cancer entered the study. Cytogenetic damage induced in peripheral blood lymphocytes of these patients was investigated at different times during the radiotherapy course using Giemsa staining and mFISH. A blood sample from each patient was taken before initiation of radiation therapy and irradiated in vitro to test for individual radiosensitivity. In addition, in vitro dose-effect curves for the induction of chromosomal exchanges by X-rays and carbon ions of different energies were measured. Results: The yield of chromosome aberrations increased during the therapy course, and the frequency was lower in patients irradiated with carbon ions as compared to patients treated with IMRT with similar target volumes. A higher frequency of aberrations was measured by increasing the target volume. In vitro, high-LET carbon ions were more effective than X-rays in inducing aberrations and yielded a higher fraction of complex exchanges. The yield of complex aberrations observed in vivo was very low. Conclusion: The investigation showed no higher aberration yield induced by treatment with a carbon-ion boost. In contrast, the reduced integral dose to the normal tissue is reflected in a lower chromosomal aberration yield when a carbon-ion boost is used instead of IMRT alone. No cytogenetic 'signature' of exposure to densely ionizing carbon ions could be detected in vivo.

Lymphocytic hypophysitis and hypothalamitis - a case report

International Nuclear Information System (INIS)

Stelmachowska, M.; Bolko, P.; Wasko, R.; Sowinski, J.; Kosinski, D.; Towpik, I.

2006-01-01

Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

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ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib.

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Okamoto, Koh; Proia, Laurie A; Demarais, Patricia L

2016-01-01

Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL) is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. It acts by inhibiting Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton's tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

T lymphocytes in the lesional skin and the levels of peripheral blood cytokines in patients with psoriasis

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İbrahim Kökçam

2011-03-01

Full Text Available In the current study, it was aimed to investigate the roles of tissue cellular immunity and serum levels of cytokines in the patients with plaque psoriasis treated with calcipotriol-betamethasone dipropionate.Materials and methods: The study included 20 patients with psoriasis. Peripheral blood and biopsy samples were collected from lesional and normal skins before and after treatment. The results were compared with each other.Results: Immunohistochemical examination revealed significant elevations of CD4+, CD8+ and CD25+ T lymphocytes in the lesional tissues when compared to that in the healthy tissues and post treatment tissue (p0.05. The levels of IL–4, IL–10, TNF-α, IFN-γ and TGF-β1 in serum were not significantly different between before and after treatment periods (p>0.05.Conclusion: Our study demonstrated that there were infiltration of CD4+ and CD8+ cell in the lesional skin and CD8+ T-lymphocytes were the dominant cell types. The improvement of the lesions and significant decreases in CD4+ and CD8+ T-cells in accordance with the treatment strongly support the hypothesis that Th lymphocytes may have prominent roles in the immunopathogenesis of the disease. However, our findings showed that sufficient T-cells still remains in the tissue, which is consistent with the chronic characteristic of the disease, and the topical treatment could not be able to prevent the activation of the disease.

Inhibitory effects of telmisartan on culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes from Xinjiang Kazakh patients with hypertension

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Sha-Sha Huang

2016-10-01

Full Text Available Introduction: Activation of T lymphocytes, for which potassium channels are essential, is involved in the development of hypertension. In this study, we explored the inhibitory effects of telmisartan on the culture and proliferation of and Kv1.3 potassium channel expression in peripheral blood CD4+ T lymphocytes derived from Xinjiang Kazakh patients with hypertension. Methods: CD4+ T-cell samples from hypertensive Kazakh patients and healthy Kazakh people were divided into healthy control, case control, telmisartan, and 4-aminopytidine groups. Changes in the expression levels of interleukin (IL-6 and IL-17 in the blood of the healthy control and case control subjects were detected by enzyme-linked immunosorbent assay. Peripheral blood CD4+ T lymphocytes were first activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Thereafter, changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and microscope photography. Changes in messenger RNA (mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and Western blots, respectively. Results: The IL-6 and IL-17 expression levels were significantly higher in the blood of the hypertensive Kazakh patients than in the healthy Kazakh people. Telmisartan inhibited T-lymphocytic proliferation, as well as the mRNA and protein expression of the Kv1.3 potassium channel in CD4+ T lymphocytes, and the inhibitory effects were time-dependent, with the strongest inhibition observed after 48 h and significantly weaker inhibition observed after 24 h of treatment. Conclusions: Telmisartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and Kv1.3 potassium channel expression in CD4+ T lymphocytes.

Profile of obinutuzumab for the treatment of patients with previously untreated chronic lymphocytic leukemia

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Hill BT

2015-08-01

Full Text Available Brian T Hill, Matt Kalaycio Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Chronic lymphocytic leukemia (CLL is a hematologic malignancy derived from a clonal population of mature B-lymphocytes characterized by relatively low CD20 antigen expression. Although the disease often takes an indolent course, the majority of patients will eventually require therapy. Standard treatment for medically fit patients includes purine analogs and/or alkylating agents in addition to the type I anti-CD20 monoclonal antibody, rituximab. This therapy is inherently myelosuppressive and can result in significant morbidity and even mortality in patients with impaired performance status due to age and/or medical comorbidities. Historically, treatment options for the elderly or frail patient population were limited to monotherapy with the oral alkylating agent, chlorambucil, rituximab, or another type I anti-CD20 monoclonal antibody ofatumumab. Recently, a newer-generation anti-CD20 monoclonal antibody, obinutuzumab, was developed for patients with CLL. Obinutuzumab is a humanized type II monoclonal antibody that appears to have more direct antibody-dependent cell-mediated cytotoxicity (ADCC and possibly more direct cytotoxicity in vitro than previously available type I antibodies. A large Phase III prospective randomized clinical trial for older patients with impaired renal function and/or significant medical comorbidities demonstrated that when compared to conventionally-dosed rituximab and chlorambucil, the combination of chlorambucil and obinutuzumab administered at a dose and schedule involving early loading doses improved response rates and progression-free survival without significantly increasing toxicity. Results of this pivotal trial led to the FDA (US Food and Drug Administration approval of obinutuzumab in combination with chlorambucil for frontline treatment of CLL. Obinutuzumab

Morphometric Characterization of Small Cell Lymphocytic Lymphoma

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Chisoi Anca

2014-11-01

Full Text Available The morphometry in histopathology is used to characterize cell populations belonging to different tissues and to identify differences in their parameters with prognostic implications. To achieve morphometric examination were selected 6 of 24 cases identified as small cell lymphocytic lymphoma. For each case analysis was done on five fields, for each field measuring the parameters of 20 cells. The studied parameters were for cytoplasm: cytoplasmic area, maximum and minimum cytoplasmic diameter, cytoplasmic perimeter; for nucleus were measured: nuclear area, minimum and maximum nuclear diameter, nuclear perimeter, nuclear contour index, nuclear ellipticity index, nuclear irregularity index. Also the nucleocytoplasmic ratio was calculated in all studied cases. Small cell lymphocytic lymphoma is characterized in morphometric terms having a small cytoplasmic area (average 29.206 and also a small nuclear area (mean 28.939 having a nucleo-cytoplasmic ratio appearance suggestive for adult lymphocyte. A nuclear contour index small value (3.946, ellipticity index value also small (3.521 and small nuclear irregularity index (3.965. Standard deviations, in any of the studied morphometric categories, is around or below 1 suggesting monomorphic cell appearance. These morphometric and microscopic features characterized mainly by a small population of adult lymphocytes, monomorphic, with rounded hipercromic nuclei, dense chromatin, support the framing into indolent lymphoma group in terms of clinical outcome.

Preoperative platelet-lymphocyte ratio is superior to neutrophil-lymphocyte ratio as a prognostic factor for soft-tissue sarcoma

International Nuclear Information System (INIS)

Que, Yi; Qiu, Haibo; Li, Yuanfang; Chen, Yongming; Xiao, Wei; Zhou, Zhiwei; Zhang, Xing

2015-01-01

Inflammation can promote tumor growth, invasion, angiogenesis and even metastasis. Inflammatory markers have been identified as prognostic indicators in various malignances. This study compared the usefulness of platelet-lymphocyte ratio (PLR) with that of neutrophil-lymphocyte ratio (NLR) for predicting outcomes of patients who underwent radical resection for soft tissue sarcoma (STS). We included 222 STS patients in this retrospective study. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease free survival (DFS). In univariate analysis, elevated PLR and NLR were both significantly associated with decreased OS. In multivariate analysis, PLR (HR: 2.60; 95 % CI: 1.17–5.74, P = 0.019) but not NLR was still identified as independent predictors of outcome. Median OS was 62 and 76 months for the high PLR and low PLR groups, respectively. High PLR and NLR were both significantly associated with shorter DFS in univariate analysis, with median DFS of 18 and 57 months in the high PLR and low PLR groups. In multivariate analysis, elevated PLR (HR: 1.77; 95 % CI: 1.05–2.97, P = 0.032) was also related to decreased DFS. Our findings provide a new and valuable clue for diagnosing and monitoring STS. Prediction of disease progression is not only determined by the use of clinical or histopathological factors including tumor grade, tumor size, and tumor site but also by host-response factors such as performance status, weight loss, and systemic inflammatory response. They also significantly affect clinical outcomes. Thus, PLR can be used to enhance clinical prognostication. Furthermore, the PLR can be assessed from peripheral blood tests that are routinely available without any other complicated expenditure, thus providing lower cost and greater convenience for the prognostication. Elevated preoperative PLR as an independent prognostic factor is superior to NLR in predicting clinical outcome in patients with STS

Defective G2 repair in Down syndrome; Effect of caffeine, adenosine and niacinamide in control and X-ray irradiated lymphocytes

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Pincheira, J.; Rodriguez, M. (Department of Cellular Biology and Genetics, University of Chile, Santiago (Chile)); Bravo, M. (Department of Pediatrics, University of Chile, Santiago (Chile)); Navarrete, M.H.; Lopez-Saez, J.F. (Department of Biology, Faculty of Science, Universidad Autonoma y CCIC, Madrid (Spain))

1994-01-01

Lymphocytes from both Down syndrome (DS) patients and age-matched control donors have been investigated to identify a possible disturbance in chromosomal G2 repair. Analyses of caffeine treatments during G2 have shown that the frequency of chromosomal aberrations is higher in DS lymphocytes than in normal lymphocytes. Likewise, G2 duration is longer in DS cells than in normal cells. In both control and DS lymphocytes, caffeine treatments increase the frequencies of chromatid breakages and decrease the average of G2 duration. The reversal of the caffeine potentiation effect by adenosine and niacinamide is higher in DS cells than in normal cells. Furthermore, ATP content per cell in DS lymphocytes is one third of that estimated in normal lymphocytes. The increase of ATP level produced by adenosine or niacinamide generally correlates with the reversal of the caffeine effect on chromosome aberrations. Under the experimental conditions tested, a good negative exponential correlation between ATP level and chromosome aberrations has been detected in both normal and DS lymphocytes which were or were not X-irradiated. Finally, we postulate a decrease in G2 repair capability of DS lymphocytes caused by a low availability of ATP and/or some other factor correlating with it. (au).

Flow cytometric analysis of lymphocytes in aplastic anemia among atomic bomb survivors

International Nuclear Information System (INIS)

Imamura, Nobutaka; Inada, Tominari; Asaoku, Hideki; Abe, Kazuhiro; Oguma, Nobuo; Kuramoto, Atsushi

1986-01-01

In 6 patients with aplastic anemia and 3 patients with pernicious anemia, lymphocyte subpopulations in the peripheral blood were measured, before and after steroid therapy, with a fluorescence-activated cell sorder using various monoclonal antibodies. The ratio of OKT4-positive lymphocytes (T4) to OKT8-positive lymphocytes (T8) in the peripheral blood was reduced in 2 patients (20 %). The T4/T8 ratio returned to normal during remission of anemia. Hematological improvement was seen after a large amount of steroid therapy in 3 patients. The number of Tac-positive cells tended to decrease and the T4/T8 ratio tended to return to normal with hematological improvement, although there was no correlation to hydrocortisone reaction. Some patients were supposed to have abnormal number of suppressor and inducer T cells. (Namekawa, K.)

Defective immunoregulatory T-cell function in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Han, T.; Ozer, H.; Henderson, E.S.; Dadey, B.; Nussbaum-Blumenson, A.; Barcos, M.

1981-01-01

Chronic lymphocytic leukemia (CLL) of B-cell origin results in the malignant proliferation of small immunoglobulin-bearing lymphocytes. There is currently a controversy in the literature regarding both the ability of this leukemic population to differentiate into mature plasma cells, as well as the ability of apparently normal T cells from these patients to regulate allogeneic B-cell differentiation. In the present study we have examined the lymphocytes of CLL patients in various clinical stages of their disease and with different surface phenotypes of their leukemic B-cell population. Our results show that leukemic CLL B cells from all 20 patients (including one patient with a monoclonal IgM paraprotein and another with a monoclonal IgG paraprotein) are incapable of further differentiation even in the absence of suppressor T cells and the presence of helper T lymphocytes. This lack of capacity to differentiate is unaffected by clinical stage, by therapy, or by the phenotype of the malignant population. Since the leukemic B population did not suppress normal allogeneic B-cell differentiation, the maturation deficit is evidently intrinsic to the leukemic clone rather than a result of activity of non-T suppressor cells. T helper function was also variably depressed in the blood of some patients with CLL, and this depression did not correlate with clinical stage, with therapy, or with the degree of lymphocytosis. Dysfunction of radiosensitive T suppressor cells was found to be the most consistent regulatory deficit of CLL T cells. Each of 11 patients whose leukemic cell population was of the μdelta, μα, or μ phenotype had both helper and suppressor cell defects

How I treat elderly or comorbid patients with chronic lymphocytic leukemia.

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Smolej, Lukás

2010-01-01

Treatment of chronic lymphocytic leukemia (CLL) has recently undergone several major changes. Most importantly, large randomized trials (CLL-8 in first line and REACH in relapse) clearly demonstrated superiority of chemoimmunotherapy consisting of fludarabine, cyclophosphamide and rituximab (FCR) over fludarabine and cyclophosphamide (FC) alone, thus establishing FCR regimen as the new gold standard in younger and physically fit patients. However, management of elderly and/or comorbid patients is still a challenging task because they cannot be treated with agressive approaches due to high risk of unacceptable toxicity. To date, no randomized trials in this patient population have improved therapeutic results over chlorambucil; therefore, this agent remains the backbone of treatment against which the new protocols should be tested. When deciding about the intensity of treatment, performance status, biological age and number as well as severity of comorbidities should be taken into account. Emerging treatment concepts for elderly/comorbid patients include combination of chlorambucil with monoclonal antibodies (rituximab, ofatumumab, GA-101), fludarabine-based regimens in reduced doses or protocols based on bendamustine and lenalidomide. Combination of high-dose steroids with rituximab represent a promising option in relapsed/refractory CLL; however, infectious toxicity remains a serious issue. Finally, ofatumumab monotherapy appears to be a safe and effective therapy for heavily pretreated patients with CLL. This article reviews the current and future possibilities in the treatment of elderly and comorbid patients with CLL.

Activated alveolar macrophage and lymphocyte alveolitis in extrathoracic sarcoidosis without radiological mediastinopulmonary involvement

International Nuclear Information System (INIS)

Wallaert, B.; Ramon, P.; Fournier, E.C.; Prin, L.; Tonnel, A.B.; Voisin, C.

1986-01-01

Cellular characteristics of BAL were investigated in 18 patients with proved extrathoracic sarcoidosis (that is, sarcoidosis that affected the skin, eyes, parotid glands, stomach, nose, kidneys, or meninges) without clinical or radiological mediastinopulmonary involvement. Computed tomography of the thorax was performed on five patients: four patients were normal, and one had enlarged lymph nodes (these enlargements were not detectable on the patient's chest roentgenogram). The results of pulmonary function tests were normal in all patients. The total BAL cell count did not differ significantly between controls and patients. Abnormal percentages of alveolar lymphocytes (from 18 to 87%) were noted in 15 out of 18 patients. SACE levels were normal in 15 patients. No pulmonary gallium uptake was detected. The chemiluminescence of AM's, whether spontaneous or PMA induced, was increased in five out of seven patients. The percentages of T3+ lymphocytes in sarcoidosis patients did not significantly differ from those in controls. The T4+:T8+ ratio was normal in four patients and slightly increased in one. Follow-up of patients showed that alveolar lymphocytosis is as lasting as extrathoracic involvement. Our data demonstrate increased percentages of lymphocytes and activated AM's in the BAL of patients with extrathoracic sarcoidosis. This may be due to the initial involvement of the respiratory tract in extrathoracic sarcoidosis or to the diffusion of activated macrophages and lymphocytes from an extrathoracic site into the lung

Tetrasomy 8 in a patient with chronic lymphocytic leukemia.

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de Oliveira, Fábio Morato; Brandão, Renata Amorim; Leite-Cueva, Sabrina Dias; de Paula Careta, Francisco; Simões, Belinda Pinto; Rego, Eduardo Magalhães; Falcão, Roberto Passetto

2010-04-15

We report a case of a 47-year-old man diagnosed with chronic lymphocytic leukemia (CLL) with two extra copies of chromosome 8. Classical cytogenetic analysis by the immunostimulatory combination of DSP30 and interleukin 2 showed tetrasomy of chromosome 8 in 60% of the metaphase cells (48,XY,+8,+8[12]/46,XY[8]). Spectral karyotype analysis confirmed the abnormality previously seen by G banding. Additionally, interphase fluorescence in situ hybridization using an LSI CEP 8 probe performed on peripheral blood cells without any stimulant agent showed tetrasomy of chromosome 8 in 54% of analyzed cells (108 of 200). To our knowledge, tetrasomy 8 as the sole chromosomal abnormality in CLL has not been previously described. The prognostic significance of tetrasomy 8 in CLL remains to be elucidated. However, the patient has been followed up in the outpatient hospital since 2004 without any therapeutic intervention and has so far remained stable. Copyright 2010 Elsevier Inc. All rights reserved.

The neutrophil to lymphocyte ratio in patients supported with extracorporeal membrane oxygenation.

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Yost, Gardner; Bhat, Geetha; Pappas, Patroklos; Tatooles, Antone

2018-04-01

The neutrophil to lymphocyte ratio (NLR) has proven to be a robust predictor of mortality in a wide range of cardiovascular diseases. This study investigated the predictive value of the NLR in patients supported by extracorporeal membrane oxygenation (ECMO) systems. This study included 107 patients who underwent ECMO implantation for cardiogenic shock. Median preoperative NLR was used to divide the cohort, with Group 1 NLR <14.2 and Group 2 with NLR ≥14.2. Survival, the primary outcome, was compared between groups. The study cohort was composed of 64 (60%) males with an average age 53.1 ± 14.9 years. Patients in Group 1 had an average NLR of 7.5 ± 3.5 compared to 27.1 ± 19.9 in Group 2. Additionally, those in Group 2 had significantly higher preoperative blood urea nitrogen (BUN) and age. Survival analysis indicated a thirty-day survival of 56.2%, with significantly worsened mortality in patients with NLR greater than 14.2, p=0.047. Our study shows the NLR has prognostic value in patients undergoing ECMO implantation. Leukocytes are known contributors to myocardial damage and neutrophil infiltration is associated with damage caused by myocardial ischemia.

Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques

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Saraswathy Radha

2000-01-01

Full Text Available Blood lymphocytes from xeroderma pigmentosum (XP and Fanconi anemia (FA patients were assessed for their sensitivity to ionizing radiation by estimating the frequency of X-ray (1 and 2 Gy-induced chromosome aberrations (CA. The frequencies of aberrations in the whole genome were estimated in Giemsa-stained preparations of lymphocytes irradiated at G0 or G2 stages. The frequencies of translocations and dicentrics involving chromosomes 1 and 3 as well as the X-chromosome were determined in slides stained by fluorescence in situ hybridization (FISH technique. An increase in all types of CA was observed in XP and FA lymphocytes irradiated at G0 when compared to controls. The frequency of dicentrics and rings was 6 to 27% higher (at 1 and 2 Gy in XP lymphocytes and 37% higher (at 2 Gy in FA lymphocytes than in controls, while chromosome deletions were higher in irradiated (30% in 1 Gy and 72% in 2 Gy than in control XP lymphocytes and 28 to 102% higher in FA lymphocytes. In G2-irradiated lymphocytes the frequency of CA was 24 to 55% higher in XP lymphocytes than in controls. In most cases the translocation frequencies were higher than the frequencies of dicentrics (21/19.

CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

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Guillaume Sarrabayrouse

2014-04-01

Full Text Available How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL-10-producing Foxp3 regulatory T cells (Treg, which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL and peripheral blood lymphocytes (PBL from healthy individuals, and those with colon cancer and irritable bowel disease (IBD, we demonstrated that CD4CD8αα (DP8α T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8α LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8α PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii identify F. prausnitzii as a major inducer of these Treg, (iii argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv provide new tools to address the systemic impact of both these Treg

The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

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Jara, Sebastian M; Carson, Kathryn A; Pai, Sara I; Agrawal, Nishant; Richmon, Jeremy D; Prescott, Jason D; Dackiw, Alan; Zeiger, Martha A; Bishop, Justin A; Tufano, Ralph P

2013-12-01

Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. Female patients of all ages with CLT and small PTCs have the least incidence of CNM. Copyright © 2013 Mosby, Inc. All rights reserved.

Infections in patients with chronic lymphocytic leukaemia: Mitigating risk in the era of targeted therapies.

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Teh, Benjamin W; Tam, Constantine S; Handunnetti, Sasanka; Worth, Leon J; Slavin, Monica A

2018-04-23

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia with infections a leading cause of morbidity and mortality. Recently there has been a paradigm shift from the use of chemo-immunotherapies to agents targeting specific B-lymphocyte pathways. These agents include ibrutinib, idelalisib and venetoclax. In this review, the risks and timing of infections associated with these agents are described, taking into account disease and treatment status. Treatment with ibrutinib as monotherapy or in combination with chemo-immunotherapies is not associated with additional risk for infection. In contrast, the use of idelalisib is associated with a 2-fold risk for severe infection and opportunistic infections. Venetoclax does not appear to be associated with additional infection risk. The evolving spectrum of pathogens responsible infections in CLL patients, especially those with relapsed and refractory disease are described, and prevention strategies (prophylaxis, monitoring and vaccination) are proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lymphocytic infundibulo-neurohypophysitis (LINH) with involvement of the hypothalamus and with coexistent focal infiltration of the brain stem: A case report

International Nuclear Information System (INIS)

Spalek, M.; Kowalska, A.

2006-01-01

Autoimmune (lymphocytic) hypophysitis is a rare disease. It was originally labeled lymphocytic adenohypophysitis (LAH) and was first described in 1962. However, when it was later realized that the autoimmune infiltrate could exclusively involve the infundibular stem and the posterior lobe, the term lymphocytic infundibulo-neurohypophysitis (LINH) was created. Review of the literature identified 39 patients with LINH, 245 with LAH, and 95 with LPH (lymphocytic pan-hypophysitis) to date. The authors present the case of a 19-year-old woman with acute bacterial infection previous to symptoms of hypopituitarism. CT and MR imaging showed tumor-like areas of intensive post-contrast enhancement without edema in the suprasellar region and in the brain stem. Based on the diagnostic investigations, LINH was diagnosed. Germinoma, sarcoidosis, tuberculosis, and bacterial hypophysitis were excluded in the diagnostic differentiation. Regression of clinical and radiological symptoms was observed after corticotherapy. Lymphocytic infundibulo-neurohypophysitis is a rare disease that should be considered in the differential diagnosis of any suprasellar and/or intrasellar mass. (author)

Quantitative modifications of T-lymphocyte subpopulations in inoperable patients irradiated with Co60 in the area of neck and interpleural space

International Nuclear Information System (INIS)

Beyer-Enke, S.A.; Strauss, L.G.; Gajzer, S.; Georgi, M.

1987-01-01

Several parameters of red and white blood components were determined in twelve patients submitted to Co 60 -irradiations for inoperable tumors in the area of neck and interpleural space. Some statistically significant, dose-dependent modifications were found for leucocytes, thrombocytes and lymphocytes. A considerable radiogenic reduction was demonstrated especially for helper cells, suppressor cells and natural killer cells. A different radiosensitivity could not be proved for these lymphocyte subpopulations. A possible influence of disease-specific endogenous as well as exogenous factors was discussed. (orig.) [de

The level of T lymphocyte subpopulation and cytokines in senile patients with stable chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Mu Xiaofen; Chen Sujuan; Cai Lili; Dong Ke

2006-01-01

To investigate the level of T-lymphocyte subsets(CD3 + , CD4 + , CD8 + )and serum IL-4, IL-8 and TNF-α in senile patients with stable chronic obstructive pulmonary disease(COPD) and provide basis in observing the inflammatory process of COPD, 50 senile patients with stable COPD and 40 senile healthy persons as control group were selected, and levels of IL-4, IL-8 and TNF-α in serum were detected by RIA method, the T-lymphocyte subset (CD3 + , CD4 + , CD8 + )of peripheral blood was measured by flow cytometry. The levels of CD3 + , CD4 + in COPD group were lower than in control group (P + IL-8 were also slightly higher in COPD group compared with that in control group, but the difference between them is not significant. CD3 + , CD4 + were lower and IL-4, TNF-α were higher in COPD group than those in control group, which means that abnormal cellular immunity function and inflammatory process still existed in the stable period of COPD. (authors)

Changes in helper and suppressor T lymphocytes following radiotherapy for breast cancer

International Nuclear Information System (INIS)

Newman, G.H.; Rees, G.J.G.; Jones, R.S.J.; Grove, E.A.; Preece, A.W.

1987-01-01

Changes in total lymphocyte, T lymphocyte, T helper and T suppressor lymphocyte numbers were studied in 22 patients with breast cancer before and after radiotherapy. T lymphocyte subsets were measured using monoclonal antibodies and fluorescence microscopy. After treatment the total lymphocyte count fell significantly and was still reduced 9 months later, but the proportion of cells labelled as T lymphocytes was unchanged during this period. The helper-suppressor ratio, which was within the normal range before radiotherapy, was significantly reduced at 3 months and 9 months after. Following treatment both T helper and T suppressor cell numbers were significantly reduced. T helper cell numbers remained reduced throughout the study period but T suppressor cell numbers showed a recovery to normal values 9 months after radiotherapy. (author)

Prognostic Value of Lipoprotein Lipase Expression Among Egyptian B-Chronic Lymphocytic Leukemia Patients

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SAAD, A.A.; EL-SHENNAWY, D.; HAMED, A.I.; EL-FEKY, M.A.; ISMAIL, M.A.; EL-HAGRACY, R.S.

2008-01-01

Background: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a highly variable clinical course. Some patients may survive for years without need for therapy while others, although they had early treatment, the outcome is unsatisfactory. The motive to find more reliable prognostic factors apart from stage, age, tumor volume and immunoglobulin heavy chain mutations is of clinical interest. Material and Methods: The study was carried out on 25 CLL patients attending Hematology Clinic at Ain Shams University Hospitals. Peripheral blood sample was taken from each patient for surface CD38 and cytoplasmic zeta-chain-associated protein tyrosine kinase (ZAP-70) by flow cytometry and lipoprotein lipase (LPL) expression by real time PCR. Results: We demonstrated statistically significant association between high level of LPL expression and significantly high LDH level, poor cytogenetic risk, ZAP- 70 expression and response to therapy ( p =0.01, 0.02, 0.04 and 0.001 respectively). Conclusion: LPL expression can serve as a new surrogate prognostic factor for CLL patients and can be used to detect patients who need early treatment

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial.

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Ali, H R; Dariush, A; Thomas, J; Provenzano, E; Dunn, J; Hiller, L; Vallier, A-L; Abraham, J; Piper, T; Bartlett, J M S; Cameron, D A; Hayward, L; Brenton, J D; Pharoah, P D P; Irwin, M J; Walton, N A; Earl, H M; Caldas, C

2017-08-01

We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown. The ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed. Of the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78-4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24-3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033-0.31; P < 0.001). Lymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

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Tang, Xingxing; Du, Peng; Yang, Yong

2017-10-01

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study.

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Rojas, Paulina Soledad; Fritsch, Rosemarie; Rojas, Romina Andrea; Jara, Pablo; Fiedler, Jenny Lucy

2011-09-30

Depressive patients often have altered cortisol secretion, an effect that likely derives from impaired activity of the glucocorticoid receptor (GR), the main regulator of the hypothalamus-pituitary-adrenal (HPA) axis. Glucocorticoids reduce the levels of brain-derived neurotrophic factor (BDNF), a downstream target of antidepressants. Antidepressants promote the transcriptional activity of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), a regulator of BDNF expression. To identify potential biomarkers for the onset of antidepressant action in depressive patients, GR and phospho-CREB (pCREB) levels in lymphocytes and serum BDNF levels were repeatedly measured during the course of antidepressant treatment. Thirty-four depressed outpatients (10 male and 24 female) were treated with venlafaxine (75mg/day), and individuals exhibiting a 50% reduction in their baseline 17-Item Hamilton Depression Rating Scale score by the 6th week of treatment were considered responders. Responders showed an early improvement in parallel with a rise in BDNF levels during the first two weeks of treatment. Non-responders showed increased GR levels by the third week and reduced serum BDNF by the sixth week of treatment. In contrast, venlafaxine did not affect levels of pCREB. We conclude that levels of BDNF in serum and GR levels in lymphocytes may represent biomarkers that could be used to predict responses to venlafaxine treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Association between neutrophil/lymphocyte ratio and coronary collateral circulation

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Mustafa Oylumlu

2012-03-01

Full Text Available Objectives: To investigate relation between neutrophil/lymphocyte ratio and coronary collateral flow.Material and methods: Eighty-two patients admittedDicle University Medical Faculty Hospital Cardiology Departmentwith diagnosis of coronary artery disease anddetected significant stenosis or occlusion at least one ofthe coronary arteries, were included to study. Age, sex,presence of diabetes mellitus and hypertension, acute/stable coronary disease, body mass index, neutrophil/lymphocyte ratio, white blood count, Rentrop scores andnumber of diseased vessel were recorded.Results: Well-developed coronary collateral circulationwas found in 33 of the patients. Forty-nine patients hadpoor coronary collateral circulation. Mean age, sex, bodymass index, presence of diabetes mellitus and hypertensionwere similar in two groups. Mean neutrophil/lymphocyteratio was lower in well-developed coronary collateralcirculation group than poor coronary collateral circulationgroup, but there was no significant differences (2.78 vs2.89, p=0.12.Conclusions: There was no association between neutron/hil lymphocyte ratio and coronary collateral circulationaccording to our data. J Clin Exp Invest 2012; 3(1:29-32

Cloning of the chromosome translocation breakpoint junction of the t(14;19) in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

McKeithan, T.W.; Rowley, J.D.; Shows, T.B.; Diaz, M.O.

1987-01-01

The authors' laboratory has reported that t(14;19)(q32;q13.1) is a recurring translocation in the neoplastic cells of patients with chronic lymphocytic leukemia. In the present study, they have analyzed the leukemic cells from one such patient with probes from the immunoglobulin heavy-chain locus, which is present on band q32 of chromosome 14. Using a probe for the α constant-region gene segments, they detected a rearranged band by Southern blot analysis. This rearranged band was cloned and mapped. A subclone free of repetitive sequences was shown to be from chromosome 19 by analysis of human-mouse somatic cell hybrids, confirming that the rearranged band contains the translocation breakpoint junction. This probe may be used to identify a gene on chromosome 19 adjacent to the breakpoint that can contribute to the malignant development of B lymphocytes

Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology

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MARISOL HERRERA-RIVERO

2013-01-01

Full Text Available Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

The Relationship Between 14C Urea Breath Test Results and Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios

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Ertan Şahin

2018-04-01

Full Text Available Aim: Neutrophil/lymphocyte ratio (NLR and platelet/lymphocyte ratio (PLR are used as inflammatory markers in several diseases. However, there are little data regarding the diagnostic ability of NLR and PLR in Helicobacter pylori. We aimed to assess the association between the 14C urea breath test (14C-UBT results and NLR and PLR in H. pylori diagnosis. Methods: Results of 89 patients were retrospectively analysed in this study. According to the 14C-UBT results, patients were divided into two groups: H. pylori (+ and H. pylori (- (control group. Haematological parameters, including hemoglobine, white blood cell (WBC count, neutrophil count, lymphocyte count, NLR, platelet count, and PLR were compared between the two groups. Results: The mean total WBC count, neutrophil count, NLR and PLR in H. pylori (+ patients were significantly higher than in the control group (p<0.001 for all these parameters. In the receiver operating characteristic curve analysis, the cut-off value for NLR and PLR for the presence of H. pylori was calculated as ≥2.39 [sensitivity: 67.3%, specificity: 79.4%, area under the curve (AUC: 0.747 (0.637-0.856, p<0.0001] and ≥133.3 [sensitivity: 61.8%, specificity: 55.9%, AUC: 0.572 (0.447-0.697, p<0.05], respectively. Conclusion: The present study shows that NLR and PLR are associated with H. pylori positivity based on 14C-UBT, and they can be used as an additional biomarker for supporting the 14C-UBT results.

DNA damage in blood lymphocytes in patients after {sup 177}Lu peptide receptor radionuclide therapy

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Eberlein, Uta; Bluemel, Christina; Buck, Andreas Konrad; Werner, Rudolf Alexander; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nowak, Carina; Scherthan, Harry [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany)

2015-10-15

The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-labelled DOTATATE/DOTATOC. The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with {sup 131}I and {sup 177}Lu. The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Measurements of RIF and the absorbed dose to the blood after systemic administration of {sup 177}Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. (orig.)

Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis.

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Tang, Haowen; Lu, Wenping; Li, Bingmin; Li, Chonghui; Xu, Yinzhe; Dong, Jiahong

2017-05-30

Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.

The effect of smoking on neutrophil/lymphocyte and platelet/lymphocyte ratio and platelet ındices: a retrospective study.

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Tulgar, Y K; Cakar, S; Tulgar, S; Dalkilic, O; Cakiroglu, B; Uyanik, B S

2016-07-01

Smoking commonly leads to death. Although the neutrophil/lymphocyte Ratio, platelet/lymphocyte ratio and platelet indices have been shown to be important for the diagnosis, prognosis and severity of some diseases, the smoking status of patients in these studies has not been well defined. In this study, we compared ratios derived from complete blood count and platelet indices to smoking status and length in smokers and non-smokers. The data of healthy males and females aged between 18-60 years who presented to our institute for a routine check-up were collected, and subjects were divided in two groups - smokers and non-smokers. The presence of medical history or laboratory results which could affect inflammatory response, formed our exclusion criteria. All complete blood count results were noted and persons' smoking habits were calculated as pack/years. White blood cell, neutrophil, basophil and eosinophil counts; mean corpuscular volume, red cell distribution width and neutrophil/lymphocyte ratio were significantly higher in smokers when compared to non-smokers (psmokers were grouped according to smoking habits; positive linear correlations were detected between pack/year and Neutrophil/lymphocyte ratio and also pack/year and plateletcrit in smokers (paffected and platelet distribution width is increased in smokers. If smokers are not excluded from studies evaluating neutrophil/lymphocyte ratio and platelet distribution width, the relationship between smoking status as well as pack/year must be determined and reported.

The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

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Khong, Hung T.; Rosenberg, Steven A.

2008-01-01

In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332–340 and SOX10: 331–340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion. PMID:12036907

Low serum albumin and total lymphocyte count as predictors of 30 day hospital readmission in patients 65 years of age or older

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Robert Robinson

2015-08-01

Full Text Available Introduction. Hospital readmission within 30 days of discharge is a target for health care cost savings through the medicare Value Based Purchasing initiative. Because of this focus, hospitals and health systems are investing considerable resources into the identification of patients at risk of hospital readmission and designing interventions to reduce the rate of hospital readmission. Malnutrition is a known risk factor for hospital readmission.Materials and Methods. All medical patients 65 years of age or older discharged from Memorial Medical Center from January 1, 2012 to March 31, 2012 who had a determination of serum albumin level and total lymphocyte count on hospital admission were studied retrospectively. Admission serum albumin levels and total lymphocyte counts were used to classify the nutritional status of all patients in the study. Patients with a serum albumin less than 3.5 grams/dL and/or a TLC less than 1,500 cells per mm3 were classified as having protein energy malnutrition. The primary outcome investigated in this study was hospital readmission for any reason within 30 days of discharge.Results. The study population included 1,683 hospital discharges with an average age of 79 years. The majority of the patients were female (55.9% and had a DRG weight of 1.22 (0.68. 219 patients (13% were readmitted within 30 days of hospital discharge. Protein energy malnutrition was common in this population. Low albumin was found in 973 (58% patients and a low TLC was found in 1,152 (68% patients. Low albumin and low TLC was found in 709 (42% of patients. Kaplan–Meier analysis shows any laboratory evidence of PEM is a significant (p < 0.001 predictor of hospital readmission. Low serum albumin (p < 0.001 and TLC (p = 0.018 show similar trends. Cox proportional-hazards regression analysis showed low serum albumin (Hazard Ratio 3.27, 95% CI [2.30–4.63] and higher DRG weight (Hazard Ratio 1.19, 95% CI [1.03–1.38] to be significant

Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly.

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Üçler, R; Aslan, M; Atmaca, M; Alay, M; Ademoğlu, E N; Gülşen, I

2016-06-01

Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels. We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18), and diabetes mellitus (n = 16) were categorized into three different groups. NLR and PLR were compared between the study groups and were evaluated according to IGF-1 levels. There were no statistically significant differences in NLR and PLR measurements among the study groups (p > 0.05). However, there were significant positive correlations between NLR and IGF-1 levels and between PLR and IGF-1 levels when all patients were evaluated (r = 0.334, p = 0.011 and r = 0.277, p = 0.035, respectively). This is the first report studying the relationship of NLR and PLR with glucose status and IGF-1 levels in acromegaly patients. Our study results suggest that subclinical inflammation may play a role in increased incidence of mortality and morbidity, which depends on uncontrolled IGF-1 levels in patients with acromegaly. © The Author(s) 2015.

How I Treat Elderly or Comorbid Patients with Chronic Lymphocytic Leukemia

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Lukáš Smolej

2010-01-01

Full Text Available Treatment of chronic lymphocytic leukemia (CLL has recently undergone several major changes. Most importantly, large randomized trials (CLL-8 in first line and REACH in relapse clearly demonstrated superiority of chemoimmunotherapy consisting of fludarabine, cyclophosphamide and rituximab (FCR over fludarabine and cyclophosphamide (FC alone, thus establishing FCR regimen as the new gold standard in younger and physically fit patients. However, management of elderly and/or comorbid patients is still a challenging task because they cannot be treated with agressive approaches due to high risk of unacceptable toxicity. To date, no randomized trials in this patient population have improved therapeutic results over chlorambucil; therefore, this agent remains the backbone of treatment against which the new protocols should be tested. When deciding about the intensity of treatment, performance status, biological age and number as well as severity of comorbidities should be taken into account. Emerging treatment concepts for elderly/comorbid patients include combination of chlorambucil with monoclonal antibodies (rituximab, ofatumumab, GA-101, fludarabine-based regimens in reduced doses or protocols based on bendamustine and lenalidomide. Combination of highdose steroids with rituximab represent a promising option in relapsed/refractory CLL; however, infectious toxicity remains a serious issue. Finally, ofatumumab monotherapy appears to be a safe and effective therapy for heavily pretreated patients with CLL. This article reviews the current and future possibilities in the treatment of elderly and comorbid patients with CLL.

Disseminated Cryptococcal Disease in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib

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Koh Okamoto

2016-01-01

Full Text Available Cryptococcus is a unique environmental fungus that can cause disease most often in immunocompromised individuals with defective cell-mediated immunity. Chronic lymphocytic leukemia (CLL is not known to be a risk factor for cryptococcal disease although cases have been described mainly in patients treated with agents that suppress cell-mediated immunity. Ibrutinib is a new biologic agent used for treatment of CLL, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. It acts by inhibiting Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor critical for B-cell survival and proliferation. Ibrutinib use has not been associated previously with cryptococcal disease. However, recent evidence suggested that treatments aimed at blocking the function of Bruton’s tyrosine kinase could pose a higher risk for cryptococcal infection in a mice model. Here, we report the first case of disseminated cryptococcal disease in a patient with CLL treated with ibrutinib. When evaluating possible infection in CLL patients receiving ibrutinib, cryptococcal disease, which could be life threatening if overlooked, could be considered.

PROGNOSTIC VALUE OF TUMOR NECROSIS FACTOR-ALPHA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

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E. N. Zotina

2016-01-01

Full Text Available The prognostic value of tumor necrosis factor-alfa (TNFα, a pro-inflammatory cytokine was studied in 140 patients with a newly diagnosed chronic lymphocytic leukemia (CLL. TNFα contents in blood serum was determined using ELISA method. A significant increase of serum TNFα was shown in patients with newly diagnosed CLL, as compared to healthy individuals. Dependence of the cytokine concentration on clnical stage and course of disease was revealed: the highest levels of serum TNFα were registered in patients with advanced disease and/or CLL progression. Distinct correlations were revealed between the studied cytokine amounts and clinical laboratory parameters reflecting the cell proliferative activity and tumor clone size. Immunochemotherapy was accompanied by a significant reduction of TNFα levels. According to the data from multivariate regression analysis. TNFα level of at the time of the diagnosis was an independent predictor of overall survival. Hence, TNFα plays an important role in CLL pathogenesis and may be used as an additional predictive factor for CLL outcomes.

The prognostic value of peripheral CD4+CD25+ T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cells-cytokine induced killer cells infusion.

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Song, Qing-Kun; Ren, Jun; Zhou, Xin-Na; Wang, Xiao-Li; Song, Guo-Hong; Di, Li-Jun; Yu, Jing; Hobeika, Amy; Morse, Michael A; Yuan, Yan-Hua; Yang, Hua-Bing; Lyerly, Herbert Kim

2015-12-01

This study aimed to assess the prognostic value of CD4+CD25+ T lymphocyte in peripheral blood among breast cancer patients treated with adoptive T lymphocytes immunotherapy. 217 patients participated in the follow-up study. CD4+CD25+ proportion was measured by flow cytometry in peripheral T cells. The median survival was estimated by Kaplan-Meier curve, Log-rank test and Cox hazard proportion regression model, between groups of CD4+CD25+ proportion more than 5% and less than or equal to 5% in peripheral T cells. Peripheral CD4+CD25+ T lymphocytes had not a relationship with progression-free survival. It was featured that above 5% peripheral CD4+CD25+ proportion of T cells was related with the median overall survival by a shorten of 51 months (p < 0.05) with the HR 1.65 (95%CI 1.04, 2.62). Above 5% CD4+CD25+proportion of T cells produced the HR to be 1.76 (95%CI 1.07, 2.87) In stage 0-II patients, and 3.59 (95%CI 1.05, 12.29) in triple negative breast cancer patients. Cellular immunity restoration recovered by adoptive T cell infusions which resulted in less proportion of peripheral CD4+CD25+T lymphocytes could be a potential prognostic indicator among early stage and triple negative patients.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios: are they useful for predicting gestational diabetes mellitus during pregnancy?

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Sargın MA

2016-04-01

Full Text Available Mehmet Akif Sargın, Murat Yassa, Bilge Dogan Taymur, Ayhan Celik, Emrah Ergun, Niyazi Tug Department of Obstetrics and Gynecology, Fatih Sultan Mehmet Research and Training Hospital, Istanbul, Turkey Objective: We aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR could be utilized to screen for gestational diabetes mellitus (GDM.Subjects and methods: NLR and PLR were assessed by retrospective analysis of 762 healthy and pregnant women with GDM. The patients were stratified into four groups, as follows: GDM (n=144, impaired glucose tolerance (n=76, only screen positive (n=238, and control (n=304.Results: The leukocyte, neutrophil, and lymphocyte counts were significantly higher in the study groups compared with the control group (P=0.001; P<0.01. There were no statistically significant differences between the groups with respect to the NLR and PLR (P>0.05.Conclusion: We do not recommend that blood NLR and PLR can be used to screen for GDM. However, increase in the leukocyte count is an important marker for GDM as it provides evidence of subclinical inflammation. Keywords: inflammation, lymphocytes, neutrophils, platelets, pregnancy

The relationship between lymphocytes activated by pokeweed mitogen and by lipopolysaccharides and their radiosensitivity

International Nuclear Information System (INIS)

Su Liaoyuan; Liu Fenju; Liu Keliang; Xu Changshao; Xu Yingdong; Geng Yongzhi

1992-07-01

Human whole blood was incubated in vitro. Lymphocytes were activated by poke-weed mitogen (PWM) and by Lipopolysaccharides (LPS). The relationship between the two kinds of lymphocytes was investigated using radioactive compound incorporation. The study showed that PWM-activated lymphocytes were able to promote the stimulating effect of LPS on B lymphocytes. The stimulating effect of PWM-activated lymphocytes was obviously decreased after they were irradiated with 10 Gy gamma rays. When PWM-activated lymphocytes and LPS-activated lymphocytes were incubated together after one of the cell populations had been exposed 10 Gy 60 Co gamma rays, the incorporation of [ 3 H] TdR was much decreased and the synergistic function disappeared, especially when the PWM-activated lymphocytes were irradiated. In cells from patients treated with 60 Co gamma rays for carcinoma of nasopharynx, the incorporation in LPS-activated lymphocytes approached normal levels while that in PWM-activated lymphocytes was reduced significantly and the stimulating effect of PWM-activated lymphocytes on LPS-activated lymphocytes was also markedly reduced. These demonstrate that PWM-activated lymphocytes have a similar function to T-helper cells and seem to be more radiosensitive than LPS-activated lymphocytes

The study of lymphocytes glucocorticoid receptor in severe head injury

International Nuclear Information System (INIS)

Li Dapei; Wang Haodan; Zhao Qihuang

1994-01-01

Glucocorticoid receptors (GCR) of peripheral lymphocytes from 14 patients with severe head injury and 11 normal volunteers are studied by means of single point method of radioligand binding assay. All these patients receive surgical therapy and glucocorticoid of routine dosage. The results show that the GCR level of these patients is lower than that of the normal, while the plasma cortisol level is much higher. These changes correlate closely to the patients' clinical outcome. It is indicated that the GCR level can reflect the degree of stress of these patients and their response to glucocorticoid therapy. Using peripheral lymphocytes instead of the brain biopsy for the measurement of GCR can reflect the GCR changes of brain tissue, it's more convenient to get the sample and more acceptable to the patients

Dose assessment by quantification of chromosome aberrations and micronuclei in peripheral blood lymphocytes from patients exposed to gamma radiation

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Silva-Barbosa, Isvania; Pereira-MagnataI, Simey; Amaral, Ademir [Pernambuco Univ., Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia - GERAR; Sotero, Graca [Fundacao de Hematologia e Hemoterapia, Recife, PE (Brazil); Melo, Homero Cavalcanti [Hospital do Cancer, Recife, PE (Brazil). Centro de Radioterapia de Pernambuco]. E-mail: isvania@uol.com.br

2005-07-15

Scoring of unstable chromosome aberrations (dicentrics, rings and fragments) and micronuclei in circulating lymphocytes are the most extensively studied biological means for estimating individual exposure to ionizing radiation (IR), which can be used as complementary methods to physical dosimetry or when the latter cannot be performed. In this work, the quantification of the frequencies of chromosome aberrations and micronuclei were carried out based on cytogenetic analyses of peripheral blood samples from 5 patients with cervical uterine cancer following radiotherapy in order to evaluate the absorbed dose as a result of partial-body exposure to 60Co source. Blood samples were collected from each patient in three phases of the treatment: before irradiation, 24 h after receiving 0.08 Gy and 1.8 Gy, respectively. The results presented in this report emphasize biological dosimetry, employing the quantification of chromosome aberrations and micronuclei in lymphocytes from peripheral blood, as an important methodology of dose assessment for either whole or partial-body exposure to IR.

Impaired Lymphocyte Profile in Schistosomiasis Patients with Periportal Fibrosis

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Luciana Santos Cardoso

2013-01-01

Full Text Available The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4+CD28+ T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4+ T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8+ T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8+ T cells, CD4+CD25high T cells, and CD4+CTLA-4+ T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4+CD25low cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.

Late-onset Epstein-Barr virus-related disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation is associated with impaired early recovery of T and B lymphocytes.

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Liu, Jiangying; Yan, Chenhua; Zhang, Chunli; Xu, Lanping; Liu, Yanrong; Huang, Xiaojun

2015-10-01

Epstein-Barr virus-related disease (EBVD) is a serious clinical complication in patients who have undergone haploidentical hematopoietic stem cell transplantation (haploHSCT). Some recipients develop EBVD relatively late after haploHSCT, and most of these patients suffer a poor outcome. This retrospective cohort study characterized the early adaptive immune recovery of patients with acute leukemia presenting with EBVD more than 100 d after haploHSCT. Patients with acute leukemia who received haploHSCT and developed EBVD 100 d later (n = 8) were compared with a matched control group without EBVD (n = 24) with regard to peripheral WBC, lymphocytes, and neutrophils (at 30, 60, and 90 d) and recoveries of B and T lymphocytes (at 30 and 90 d, via immunophenotyping/flow cytometry). Ninety days after haploHSCT, the median values of WBCs and lymphocytes, and the recoveries of CD19(+) B cells and CD4(+) , CD8(+) , and CD4(+) CD45RO(+) T cells, were significantly lower in patients who developed EBVD, relative to the control group. These results suggest a significant association between deficient early recovery of B and T lymphocytes and the development of late-onset EBVD after haploHSCT. Our observation could facilitate clinical intervention and the improvement of overall survival of patients undergoing haploHSCT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Management of chronic lymphocytic leukemia.

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Stilgenbauer, Stephan; Furman, Richard R; Zent, Clive S

2015-01-01

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for "active disease," which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease.

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Mattoo, Hamid; Mahajan, Vinay S; Maehara, Takashi; Deshpande, Vikram; Della-Torre, Emanuel; Wallace, Zachary S; Kulikova, Maria; Drijvers, Jefte M; Daccache, Joe; Carruthers, Mollie N; Castelino, Flavia V; Stone, James R; Stone, John H; Pillai, Shiv

2016-09-01

IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4(+) T cells constitute the major inflammatory cell population in IgG4-RD lesions. We used an unbiased approach to characterize CD4(+) T-cell subsets in patients with IgG4-RD based on their clonal expansion and ability to infiltrate affected tissue sites. We used flow cytometry to identify CD4(+) effector/memory T cells in a cohort of 101 patients with IgG4-RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4(+)SLAMF7(+) cytotoxic T lymphocytes (CTLs) and CD4(+)GATA3(+) TH2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. CD4(+) effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG4-RD. Next-generation sequencing revealed prominent clonal expansions of these CD4(+) CTLs but not CD4(+)GATA3(+) memory TH2 cells in patients with IgG4-RD. The dominant T cells infiltrating a range of inflamed IgG4-RD tissue sites were clonally expanded CD4(+) CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4(+) CTLs. IgG4-RD is prominently linked to clonally expanded IL-1β- and TGF-β1-secreting CD4(+) CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4(+) T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Lymphocytic infiltration of bladder after local cellular immunotherapy.

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Ingram, M; Bishai, M B; Techy, G B; Narayan, K S; Saroufeem, R; Yazan, O; Marshall, C E

2000-01-01

This is a case report of a patient who received cellular immunotherapy, in the form of local injections of autologous stimulated lymphocytes (ASL) into individual tumors in the urinary bladder. A major consideration in cellular immunotherapy being the ability of immune cells to reach all target areas, we hypothesized that direct delivery of effector cells into individual bladder tumors might assure such access. ASL were generated by exposing the patient's PBL to phytohemagglutinin and culturing them in the presence of IL-2 to expand the population. ASL were injected into the base of individual bladder tumors three times at intervals of 3 weeks. The patient died of a myocardial infarct, unrelated to cell therapy, 20 days after the third injection. An autopsy was performed. Histological sections of the bladder showed extensive lymphocytic infiltration of virtually the entire organ. No conclusions about the therapeutic efficacy of local immunotherapy using ASL are possible. Nevertheless, the observations reported, taken together with reports of therapeutic efficacy of other immunotherapy regimens in the management of bladder cancer, suggest that ready access of stimulated lymphocytes to all regions of the organ may account, in part, for the relatively high rate of therapeutic success reported for various immunotherapy regimens for this malignancy.

Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance

International Nuclear Information System (INIS)

McElduff, A.; Hedo, J.A.; Taylor, S.I.; Roth, J.; Gorden, P.

1984-01-01

The insulin receptor degradation rate was examined in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. The insulin receptors were surface labeled using Na 125 I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup

The Predictive Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratio for the Effusion Viscosity in Otitis Media With Chronic Effusion.

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Elbistanli, Mustafa Suphi; Koçak, Hasan Emre; Acipayam, Harun; Yiğider, Ayşe Pelin; Keskin, Mehmet; Kayhan, Fatma Tülin

2017-05-01

The objective of the authors' study was to investigate the predictive value of the neutrophil-lymphocyte rate (NLR) and platelet-lymphocyte rate (PLR) in otitis media with effusion and the correlation of the effusion type with these ratios. Retrospective case-control study. One hundred twenty-six pediatric patients diagnosed otitis media with chronic effusion and had ventilation tube inserted between October 2015 and July 2016 were included in the study group and 124 healthy children, who applied for the routine examination and had blood count analysis, were included in the control group. The patients in the study group were divided into 2 groups regarding the effusion viscosity, which was obtained from the patients' operation files. Seventy-one patients were included in the serous group and 55 patients in the mucous group. The NLR and PLR rates of the groups were compared and statistically evaluated. The average NLR and PLR rates were significantly higher in the study group than in the control group (P = 0.000, P = 0.004 respectively). Comparison of the serous and mucous groups with the control group revealed a significant difference between the control group and the serous group regarding the NLR and PLR (P = 0.000; P = 0.000 respectively), but not between the control group and mucous group (P = 0.694; P = 0.691 respectively). Neutrophil-lymphocyte rate and PLR had a predictive value for otitis media with effusion and additionally it was a laboratory indicator supporting the typing of the viscosity of the fluid accumulated in the middle ear.

Appearance and Disappearance of Chronic Myeloid Leukemia (CML) in Patient with Chronic Lymphocytic Leukemia (CLL)

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Payandeh, Mehrdad; Sadeghi, Edris; Khodarahmi, Reza; Sadeghi, Masoud

2014-01-01

Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common leukemias of the elderly (>43 year). However, the sequential occurrence of CML followed by CLL in the same patient is extremely rare. In our report, a 52-year-old female was diagnosed with CLL (type of bone marrow (BM) infiltration was nodular and interstitial) and was treated with chlorambucil. 64 months after the diagnosis of CLL, she developed CML. She was treated with imatinib (400mg/day). After a fe...

The influence of radio- and chemotherapy on DNA repair of peripheral lymphocytes of tumor patients

International Nuclear Information System (INIS)

Klein, W.; Alth, G.; Klein, H.; Koren, H.

1979-07-01

The influence of radiotherapy and chemotherapy, respectively, on DNA excision repair was investigated in lymphocytes of the peripheral blood of 10 and 5 patients with malignancies. No effects on DNA repair were found using only betatrone of 60 Co-irradiation under normal conditions. Combination of both irradiation schedules over a longer period of therapy provoked an inhibition of DNA repair. Chemotherapy inhibits DNA repair immediately after starting therapy, but after relatively short time, the extent of DNA repair increases above normal level. (author)

Correlation between micronuclei frequency in peripheral blood lymphocytes and retention of 131-I in thyroid cancer patients

International Nuclear Information System (INIS)

Vrndic, O.B.; Milosevic-Djordjevic, O.M.; Mijatovic Teodorovic, L.C.; Zivancevic Simonovic, S.T.; Jeremic, M.Z.; Stosic, I.M.; Grujicic, D.V.

2013-01-01

Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50±6.90 vs. 27.10±19.50 MN) and significantly decreased the CBPI (1.52±0.20 vs. 1.38±0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined. (author)

[Lymphocytic Clonal Expansion in Adult Patients with Epstein-Barr Virus-Associated Lymphoproliferative Disease].

Science.gov (United States)

Zhong, Feng-Luan; Zhang, Hong-Yu; Zhang, Qian; Feng, Jia; Zhang, Wen-Li; Xu, Lei; Xu, Hai-Chan; Wen, Juan-Juan; Meng, Qing-Xiang

2017-12-01

To explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease. Peripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot. FCM showed only 1 case with clonal TCRVβ in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot. Detecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.

Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

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Bouzouita Kamel

2004-09-01

Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer

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Wild, Aaron T. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Herman, Joseph M.; Dholakia, Avani S.; Moningi, Shalini [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Lu, Yao [Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Rosati, Lauren M.; Hacker-Prietz, Amy; Assadi, Ryan K.; Saeed, Ali M. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Pawlik, Timothy M. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Jaffee, Elizabeth M.; Laheru, Daniel A. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Tran, Phuoc T. [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Weiss, Matthew J.; Wolfgang, Christopher L. [Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ford, Eric [Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington (United States); Grossman, Stuart A. [Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ye, Xiaobu [Department of Oncology Biostatistics, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah G., E-mail: sbatkoy2@jhmi.edu [Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2016-03-01

Purpose: Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). Methods and Materials: Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. Results: Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm{sup 3}) than in CRT (344.6 cm{sup 3}; P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm{sup 3} vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002). Conclusions: SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling

Treatment Sequencing in a Chronic Lymphocytic Leukemia Patient with Central Nervous System Involvement

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Filipa Mousinho

2018-01-01

Full Text Available Early-stage chronic lymphocytic leukemia (CLL with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration. Importantly, this response has been maintained with ibrutinib monotherapy for more than 12 months.

Biodistribution of radiolabeled lymphocytes

International Nuclear Information System (INIS)

Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

1985-01-01

Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

Evaluation of lymphocytic exudative pleural effusion with pleural biopsy

International Nuclear Information System (INIS)

Khurram, M.; Jaffery, A.H.; Khar, Hamama-tul-Bushra; Malik, M.F.; Javed, S.; Burki, U.F.; Khan, B.A.; Ali, A.

2002-01-01

Objective: Evaluation of lymphocytic exudative pleural effusion by histopathological examination of pleural biopsy in patients with suspected tuberculous or malignant pleural effusion. Place and Duration of Study: The study was conducted at Pulmonology Department, Pakistan Institute of Medical Sciences, Islamabad and DHQ Teaching Hospital, Rawalpindi for two years 1999-2000. Subjects and Methods: A total of 120 patients with exudative pleural effusion underwent closed pleural biopsy with Abram's needle in standard way. Average 4 biopsy specimens were obtained in each patient which were examined histopathologically. Patients in whom a definite diagnosis was not possible were further investigated with repeat pleural biopsy, sputum examinations, bronchoscopy etc. Results definite histopathological diagnosis with pleural biopsy was possible in 59 (49.16% patients, including 13 diagnosed on repeat pleural biopsy. Two commonest diagnoses made were tuberculosis and adenocarcinoma, 64.40% and 13.55% respectively. Conclusion: Histopathological evaluation of pleural biopsy specimens can lead to diagnosis in 49.16% patients with exudative lymphocytic pleural effusion. (author)

S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Brown, P D; Diamant, Marcus; Jensen, P O

1999-01-01

Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential...

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients

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Mélanie Saint-Jean

2018-01-01

Full Text Available Immunotherapy for melanoma includes adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TILs. This monocenter retrospective study was undertaken to evaluate the efficacy and safety of this treatment of patients with advanced melanoma. All advanced melanoma patients treated with TILs using the same TIL expansion methodology and same treatment interleukin-2 (IL-2 regimen between 2009 and 2012 were included. After sterile intralesional excision of a cutaneous or subcutaneous metastasis, TILs were produced according to a previously described method and then infused into the patient who also received a complementary subcutaneous IL-2 regimen. Nine women and 1 man were treated for unresectable stage IIIC (n=4 or IV (n=6 melanoma. All but 1 patient with unresectable stage III melanoma (1st line had received at least 2 previous treatments, including anti-CTLA-4 antibody for 4. The number of TILs infused ranged from 0.23 × 109 to 22.9 × 109. Regarding safety, no serious adverse effect was reported. Therapeutic responses included a complete remission, a partial remission, 2 stabilizations, and 6 progressions. Among these 4 patients with clinical benefit, 1 is still alive with 9 years of follow-up and 1 died from another cause after 8 years of follow-up. Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. The therapeutic effect of combining TILs with new immunotherapies needs further investigation.

The platelet-to-lymphocyte ratio as a predictor of patient outcomes in ovarian cancer: a meta-analysis.

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Ma, X-M; Sun, X; Yang, G-W; Yu, M-W; Zhang, G-L; Yu, J; Zhang, Y; Wang, X-M

2017-10-01

The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a meta-analysis to estimate the prognostic value of the PLR in ovarian cancer. We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference = 63.57, 95% CI 39.47-87.66, p < 0.00001). An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer.

Clinical significance of measurement of changes of serum IL-2, SIL-2R levels, B lymphocyte number and T-cell subsets after chemotherapy in patients with malignant hydatidiform mole

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Zhang Guangcai

2007-01-01

Objective: To study the clinical significance of changes of serum IL-2, SIL-2R level, peripheral blood B lymphocyte number and T-cell subsets after chemotherapy in patients with malignant hydatidiform mole. Methods: Serum IL-2 ( with RIA), SIL-2R level (with ELISA) and peripheral blood B lymphocytes number as well as T subsets (with monoclonal antibody technique) were measured both before and after chemotherapy in 32 patients with malignant hydatidiform mole as well as in 35 controls. Results: Before chemotherapy serum SIL-2R level and B lymphocyte were significantly higher in the patients than those in controls (P<0.01), while the serum IL-2 level, CD3, CD4, CD4/CD8 were significantly lower (P<0.01). Six months after chemotherapy the levels changed markedly toward normal, but remained significantly different from those in controls (P<0.05). Conclusion: Abnormal immuno-regulation were present in patients with malignant mole. (authors)

THE CHANGES IN SEMEN LYMPHOCYTE SUBPOPULATION’S RATIO IN MEN INFERTILITY

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A. V. Semenov

2007-01-01

Full Text Available Abstract. The aim of present study was to investigate the ratios of semen lymphocyte subpopulations in males with infertility. Twenty-six men (20 to 45 years old suffering from different genital diseases (chronic prostatitis, idiopathic varicocoele, testicular atrophy were enrolled into the study. Six healthy age-matched normozoospermic male volunteers with normal fertility comprised a control group. Lymphocyte phenotyping was performed by flow cytometric technique. The patients with pathospermia showed increased numbers of CD25+ lymphocytes (p < 0.05, and unchanged levels of CD95+ cells, thus leading to increased CD25+/CD95+ ratio. In the patients with normozoospermia, the value of this index was 0.94±0.18. Increase of this parameter to > 1.2, as well as its reduction to < 0.7 was associated with sterility. We suggest that suppressed apoptosis of activated lymphocytes in semen may be potentially dangerous to spermatogenesis, since both immune response and associated inflammatory reactions can cause nonspecific lesions of surrounding tissues, and induction of pathospermia.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

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John E. Mullinax

2018-03-01

Full Text Available PurposeAdoptive cell therapy (ACT using tumor-infiltrating lymphocytes (TIL for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL.Experimental designThirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS, and overall survival (OS.ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92% received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 1.0 × 1011 TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%, four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1–29.9 months. Grade ≥ 3 immune-related adverse events included hypothyroidism (3, hepatitis (2, uveitis (1, and colitis (1.ConclusionIpilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma.

Science.gov (United States)

Mullinax, John E; Hall, MacLean; Prabhakaran, Sangeetha; Weber, Jeffrey; Khushalani, Nikhil; Eroglu, Zeynep; Brohl, Andrew S; Markowitz, Joseph; Royster, Erica; Richards, Allison; Stark, Valerie; Zager, Jonathan S; Kelley, Linda; Cox, Cheryl; Sondak, Vernon K; Mulé, James J; Pilon-Thomas, Shari; Sarnaik, Amod A

2018-01-01

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 10 (2.3 × 10 10 to 1.0 × 10 11 ) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

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Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Clinical significance of determination of changes of serum TNF-α levels, peripheral B lymphocyte count and T lymphocyte subsets distribution pattern in patients with pregnancy induced hypertension syndrome

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Zhao Wenjuan

2006-01-01

Objective: To explore the changes of serum TNF-α levels, peripheral B cell count and T subsets distribution pattern in patients with pregnancy induced hypertension syndrome. Methods: Serum TNF-α levels (with RIA), peripheral B cell count as well as T subsets (with monoclonal technique) were examined in 34 patients with pregnancy induced hypertension syndrome and 35 controls. Results: The serum TNF-α levels and B lymphocytes count were significantly higher than those in controls (P 3 , CD 4 , CD4/CD8 ratio were significantly lower than those in controls (P<0.01). Conclusion: Pregnancy induced hY- pertension syndrome is a kind of autoimmune diseases with abnormal immunoregulation. (authors)

Baseline neutrophil-lymphocyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation

International Nuclear Information System (INIS)

Shen, Lijun; Zhang, Hui; Liang, Liping; Li, Guichao; Fan, Ming; Wu, Yongxin; Zhu, Ji; Zhang, Zhen

2014-01-01

The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). An elevated baseline NLR is a valuable and easily available prognostic factor for OS in

Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

KAUST Repository

Hill-Cawthorne, Grant A.

2011-11-05

Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.