Alterations In Peripheral Lymphocytes Research Articles

Expression of proBDNF/p75NTR in peripheral blood lymphocytes of patients with sepsis and its impact on lymphocyte differentiation.

Sepsis is a life-threatening organ dysfunction caused by the host's imbalanced response to infection. Due to lack of effective treatments, it has always been the difficulty and focus of clinical treatment of sepsis. Studies have shown that pro-brain-derived neurotrophic factor (proBDNF) binds to the high-affinity total neurotrophic factor p75 neurotrophin receptor (p75NTR), which activates downstream signaling cascades and disrupts immunological inflammation and plays an important role in the progression of sepsis. This study aims to explore the expression changes of lymphocyte-derived proBDNF/p75NTR in patients with sepsis and its effect on lymphocyte differentiation. From the healthy donors (control group, n=40) and sepsis patients (sepsis group, n=40) admitted to the hospital for the first time, peripheral blood samples and blood routine clinical detection indicators were obtained. By using flow cytometry, the proportion of lymphocyte subsets and their expression of proBDNF/p75NTR were examined. The peripheral blood lymphocytes were isolated from the control group and incubated with lipopolysaccharide (LPS). Flow cytometry analysis technology was used to detect the expression of proBDNF/p75NTR on LPS-treated lymphocyte subsets. On this basis, we investigated the effects on lymphocyte differentiation by inhibiting p75NTR. White blood cell count, neutrophil count, and neutrophil percentage of the patients in the sepsis group at admission were significantly higher than those in the control group; on the contrary, lymphocyte count and lymphocyte percentage in the sepsis group were lower than those in the control group (all P<0.001). The patients in the sepsis group had considerably greater neutrophil/lymphocyte and monocyte/lymphocyte ratios than those in the control group (both P<0.05). In the peripheral blood of sepsis patients, proBDNF expression was upregulated on CD19+ B cells, whereas p75NTR expression was elevated on B cells, CD4+ T cells, and CD8+ T cells (all P<0.05). ProBDNF/p75NTR expression was upregulated by LPS stimulation in vitro in peripheral blood cells of the control group (P<0.05), and this tendency was similar to the expression alterations in peripheral lymphocytes of the sepsis group. Inhibition of p75NTR increased CD4+ T cell and CD19+ B cell percentages, cytokine expression of IL-4 and IL-10, and reduced IL-1β and IL-6 production (all P<0.05). The immunosuppressive state of sepsis patients is indicated by a reduction in lymphocyte count and an increase in the proportion of inactive neutrophils. ProBDNF/p75NTR expression is upregulated in the peripheral blood lymphocytes of sepsis patients, and p75NTR inhibition may control lymphocyte differentiation involved in sepsis progression.

Evaluation of Chromosomal Alteration in Electrical Workers Occupationally Exposed to Low Frequency of Electro Magnetic Field (EMFs) in Coimbatore Population, India

Extremely low frequency electro magnetic fields (EMFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. An increased number of chromosomal alterations in peripheral lymphocytes are correlated with elevated incidence of cancer. The aim of the present study was to assess occupationally induced chromosomal damage in EMF workers exposed to low levels of radiation. We used conventional metaphase chromosome aberration (CA) analysis and the micronucleus (MN) assay as biological indicators of non ionizing radiation exposure. In the present study totally 70 subjects were selected including 50 exposed and 20 controls. Informed written consent was obtained from all participants and the study was performed in accordance with the Declaration of Helsinki and the approval of the local ethical committee. A higher degree of CA and MN was observed in exposed subjects compared to controls, the frequency of CA being significantly enhanced with long years of exposure (P<0.05). Moreover increase in CA and MN with age was noted in both exposed subjects and controls, but was significantly greater in the former. The results of this study demonstrated that a significant induction of cytogenetic damage in peripheral lymphocytes of workers occupationally exposed to EMFs in electric transformer and distribution stations. In conclusion, our findings suggest that EMFs possess genotoxic capability, as measured by CA and MN assays; CA analysis appeared more sensitive than other cytogenetic end-points. It can be concluded that chronic occupational exposure to EMFs may lead to an increased risk of genetic damage among electrical workers.

Old beagle dogs have lower faecal concentrations of some fermentation products and lower peripheral lymphocyte counts than young adult beagles

The effects of age on microbiota composition, gut fermentation end-product formation and peripheral lymphocyte numbers were compared between old and young adult Beagle dogs fed four kibble diets differing in yeast cell wall contents. The experiment had a double 4 × 4 Latin square design, one with four mature dogs (4 years old) and the other with four old dogs (10 years old), with four replicates (diets) per dog. In each period a 15 d adaptation period preceded a 5 d total collection of faeces for the digestibility trial. On day 21, fresh faecal samples were collected for the determination of bacterial enumeration, pH, biogenic amine and short-chain fatty acid. Flow cytometry was used for immunophenotypic evaluation. Dogs were fed four kibble diets with similar composition with 0, 0.15, 0.30 and 0.45 % of yeast cell wall (as-fed), respectively. Data were evaluated using general linear models of Statistical Analysis Systems statistical software (P < 0.05). No evidence of a difference in faecal bacteria counts between ages was found (total aerobes, total anaerobes, Bifidobacterium, Lactobacillus, Clostridium and Escherichia coli: P>0.15). Faecal concentrations of butyrate, histamine, agmatine and spermine were lower (P ≤ 0.05) and faecal pH was higher (P = 0.03) in older dogs than in mature adult dogs, suggesting an alteration in bacterial metabolic activity, or in the rate of intestinal absorption of these compounds. Concentrations of T-lymphocytes, T-cytotoxic lymphocytes and B-lymphocytes were also lower (P ≤ 0.01) in older dogs than in mature adult dogs. The study confirmed alterations in peripheral lymphocytes and revealed a reduced concentration of some fermentation end products in the colon of old dogs.

Peripheral lymphocyte reduction in severe acute pancreatitis is caused by apoptotic cell death

To investigate impairment of cellular immunity in severe acute pancreatitis, alterations of peripheral lymphocytes in acute pancreatitis were examined. In 48 patients with severe acute pancreatitis, the mean peripheral lymphocyte count on admission was 959 ± 105/mm 3, and it was significantly decreased in the patients with subsequent infection (623 ± 90/mm 3) in comparison to those without infection (1084 ± 135/mm 3). According to an analysis of lymphocyte subsets, although both B and T lymphocytes were decreased in peripheral circulation in the patients with infection, it was primarily CD8-positive lymphocytes that decreased in these subsets. Cell cycle analysis of lymphocytes collected from these patients indicated that apoptotic changes occurred after 24 hours' incubation in lymphocytes from patients with severe pancreatitis but not in lymphocytes from healthy control subjects. In a rat model of experimental necrotizing pancreatitis, total peripheral lymphocytes and T lymphocytes were significantly decreased 5 hours after induction of pancreatitis. In severe pancreatitis, peripherallymphocytes are eliminated from systemic circulation possibly as a result of apoptosis. It has been suggested that impairment of cellular immunity due to peripheral lymphocyte apoptosis is linked to the development of subsequent infectious complications in acute pancreatitis.

Genetic factors which regulate alcohol drinking behavior and their effects on health status

High alcohol sensitivity common among Orientals is mainly due to genetic polymorphism in the low K(m) aldehyde dehydrogenase (ALDH2) gene. The relation of the ALDH2 genotype to alcohol sensitivity and drinking behavior was investigated in a Japanese occupational population. The frequency of alcohol-associated symptoms generally increased in the order of the typical homozygote, heterozygote, and atypical homozygote. Both drinking frequency and amounts of alcohol consumption were also significantly affected by the polymorphism. Polymorphism in the alcohol dehydrogenase beta-subunit (ADH2 gene) appeared to contribute to skin flushing post-alcohol exposure but not to alcohol drinking behavior. Multivariate analysis revealed that high alcohol consumption, the ALDH2*1/*1 genotype, and high daily hassles levels significantly contribute to the prevalence of those with a high problem-drinking score in an occupational population. In the study to assess the effects of the ALDH2 polymorphism and alcohol use on the induction of chromosome alterations in peripheral lymphocytes, we found that lymphocytes from habitual drinkers with the atypical ALDH2 genotypes had significantly higher frequencies of sister-chromatid exchange (SCE) than those from the typical ALDH2 genotype. We also measured acetaldehyde reversibly bound to hemoglobin (HbAA). In volunteers with the ALDH2*1/*2 genotype, the HbAA levels increased immediately after the drink and the elevated levels persisted up to 48 h. Among male workers, HbAA levels were significantly correlated with the recent alcohol consumption levels in both the ALDH2*1/*1 and ALDH2*1/*2 genotypes. However, the slope was much steeper in the ALDH2*1/*2 than in the ALDH2*1/*1. SCE and HbAA may be utilized as a good biomarker for health problems in the atypical ALDH2 genotype. Further extensive studies are required for evaluation of the interactive effects of genetic and environmental factors on alcohol-related health problems.

Chromosomal alterations in peripheral lymphocytes of female cabin attendants

Purpose: To analyse lymphocyte chromosomes from female cabin attendants flying the North Atlantic route. Materials and methods: Peripheral lymphocytes from 58 cabin attendants and 29 controls, all female, were cultured and analyzed for structural chromosomal aberrations and sister chromatid exchanges (SCE). Cytogenetic data from 56 age-matched females from Berlin investigated between 1994 and 1996 as part of routine medical checks were used as an additional control group. Results: The mean frequencies of dicentric and ring chromosomes per 1000 cells amount to 1.3 +/- 0.2 in cabin attendants, 1.4 +/- 0.2 in ground personnel and 1.3 +/- 0.2 in the Berlin control group. Sister chromatid exchanges were found at mean frequencies of 7.0 +/- 0.1, 6.8 +/- 0.1 and 6.8 +/- 0.2 per cell respectively in the three groups. Conclusions: When compared with controls, cabin attendants have no elevation of the frequencies of dicentric and ring chromosomes and SCE.

Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes.

Excessive drinking of alcohol is now widely known to be one of the major lifestyle choices that ca effect health. Among the various effects of alcohol drinking, cytogenetic and other genotoxic effects are of major concern from the viewpoint of prevention of alcohol-related diseases. Alcohol is first metabolized to acetaldehyde, which directly causes various types of chromosomal DNA lesions and alcohol-related diseases, and is then further detoxified to the much less toxic metabolite acetate. About 50% of Oriental people are deficient in the aldehyde-dehydrogenase 2 isozyme (ALDH2) that can most efficiently detoxify acetaldehyde. We have performed a series of experiments to investigate how the genetic deficiency in ALDH2 affects the behavioral pattern for alcohol drinking and the sensitivity of peripheral lymphocytes to the induction of chromosome alterations by exposure to alcohol and alcohol-related chemicals. We found great effects of the ALDH2 genotypes on alcohol sensitivity and alcohol-drinking behavior. We also show that lymphocytes from habitual drinkers with the deficient ALDH2 enzyme had significantly higher frequencies of sister chromatid exchanges than those from ALDH2-proficient individuals.

Low K m Aldehyde Dehydrogenase (ALDH2) Polymorphism, Alcohol-Drinking Behavior, and Chromosome Alterations in Peripheral Lymphocytes

Low K m Aldehyde Dehydrogenase (ALDH2) Polymorphism, Alcohol-Drinking Behavior, and Chromosome Alterations in Peripheral Lymphocytes

Chromosome alterations in peripheral lymphocytes as indices of lifestyle and genotoxicity

Short-term cultures of human lymphocytes were used to investigate the in vitro metabolism of benzene and its genotoxicity, and to monitor genetic health effects of lifestyles. Metabolic (S9) activation of benzene and its metabolites, catechol, hydroquinone, and phenol, caused an increase in sister-chromatid exchanges (SCEs) with different optimal concentrations of S9 mix for converting each compound into further reactive forms. The data indicate that catechol and hydroquinone can be optimally metabolized to produce reactive species, presumably benzo(semi)quinones, under conditions of lower metabolic activity than those necessary for phenol and benzene. We have further investigated the correlations between chromosome alterations (SCEs, structural aberrations and micronuclei) in peripheral lymphocytes and individual lifestyles. Healthy lifestyles, or "good health practices" examined were 1) not smoking, 2) not drinking too much alcohol, 3) doing physical exercise regularly, 4) sleeping more than 6 h per night, 5) keeping nutritional balance in meals, 6) not snacking, 7) having breakfast everyday, and 8) not having too much perceived stress. The persons were categorized into 3 groups having good, moderate and poor lifestyles by the number of good health practices they do. Mean frequencies of chromosome alterations in lymphocytes from men with poor lifestyles have been shown to be significantly higher than those in cells from men having good lifestyles.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative and functional restorations and alterations of peripheral lymphocytes in patients with autologous spleen implantation

To reduce the risk of severe infections in splenectomized patients, new methods for splenic preservation or heterotopic autologous spleen implantation have been established. In the latter case, the immunological and functional benefits are still under discussion. In this study we compared immunological parameters in 16 splenectomized patients with and without heterotopic autologous spleen implantation with a nonsplenectomized control group. The total lymphocyte counts--T-cells, CD4+ -, as well as CD8+ - lymphocytes, CD16+ - and B-cells--were highly elevated in both groups, whereby the B-cells were relatively and absolutely higher in the implanted group than in the nonimplanted group. Splenectomized patients had a significantly reduced serum IgM level. The serum IgM of patients with splenic autotransplantation was not significantly lower than that of the controls. In contrast to the impaired in vitro immunoglobulin synthesis in the splenectomized group, the autotransplanted patients showed a normal PWM-induced IgG and IgM synthesis and an increased IgA production compared with the controls. The latter results support the findings of elevated serum IgA levels in this group. The mitogenic-induced proliferation with PHA, ConA, PWM, and OKT3 was not clearly different within the tested groups. The results may indicate a benefit of autologous spleen implantation in regard to the humoral immune response.