scholarly journals Acute exposure to paraquat affects the phenotypic differentiation of substantia nigra microglia in rats

Author(s):  
Wendi Zhang ◽  
Xiaobei Fan ◽  
Zhuo Fan ◽  
Bailin Wu ◽  
Mengchao Wang ◽  
...  

Abstract The toxicity of paraquat (PQ), a bipyridine cationic herbicide, to the lung and kidney has been widely recognized, but the acute toxic effects of PQ on the nervous system have received little attention. The aim of this study was to explore changes in the phenotypic differentiation of microglia in rats caused by acute PQ exposure. We found that acute PQ exposure induced pyknosis, edema and apoptosis in substantia nigra neurons. The results of immunohistochemistry and western blotting showed that the number of activated microglia increased, the number of microglia branches decreased and the length became shorter in the early stage of exposure to 25 mg/kg PQ. We then compared the mean fluorescence intensity of iNOS and ARG1. In the early stage of acute 25 mg/kg PQ exposure, the number of M1 phenotypes of microglia increased; in contrast, in the early stage of acute 45 mg/kg PQ exposure, the number of M2 phenotypes of microglia increased. On the 69th day, the expression of iNOS and ARG1 increased in the 25 mg/kg and 45 mg/kg PQ exposure groups. In sum, changes in microglia phenotypic differentiation were related to exposure dose and exposure time.

1999 ◽  
Vol 86 (3) ◽  
pp. 970-976 ◽  
Author(s):  
Stephan F. van Eeden ◽  
John Granton ◽  
Jennifer M. Hards ◽  
Barbara Moore ◽  
James C. Hogg

The pulmonary vascular bed is an important reservoir for the marginated pool of leukocytes that can be mobilized by exercise or catecholamines. This study was designed to determine the phenotypic characteristics of leukocytes that are mobilized into the circulation during exercise. Twenty healthy volunteers performed incremental exercise to exhaustion [maximal O2consumption (V˙o2 max)] on a cycle ergometer. Blood was collected at baseline, at 3-min intervals during exercise, atV˙o2 max, and 30 min after exercise. Total white cell, polymorphonuclear leukocyte (PMN), and lymphocyte counts increased with exercise toV˙o2 max( P < 0.05). Flow cytometric analysis showed that the mean fluorescence intensity of L-selectin on PMN (from 14.9 ± 1 at baseline to 9.5 ± 1.6 atV˙o2 max, P < 0.05) and lymphocytes (from 11.7 ± 1.2 at baseline to 8 ± 0.8 atV˙o2 max, P < 0.05) decreased with exercise. Mean fluorescence intensity of CD11b on PMN increased with exercise (from 10.2 ± 0.6 at baseline to 25 ± 2.5 atV˙o2 max, P < 0.002) but remained unchanged on lymphocytes. Myeloperoxidase levels in PMN did not change with exercise. In vitro studies showed that neither catecholamines nor plasma collected atV˙o2 maxduring exercise changed leukocyte L-selectin or CD11b levels. We conclude that PMN released from the marginated pool during exercise express low levels of L-selectin and high levels of CD11b.


2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Yanmin Wan ◽  
Jing Wang ◽  
Haizhu Zhou ◽  
Zhidong Hu ◽  
Xiaonan Ren ◽  
...  

Previous studies suggested that both the frequency and the mean fluorescence intensity (MFI) of cytokine secreting T cells could be of great value for immunogenicity evaluation of a vaccine. In this study, by constructing epitope-based DNA vaccines encoding a previously identified CD8+T cell epitope, we investigated the influence of multiplying epitope copies on both the frequency and the MFI of specific IFN-γsecreting CD8+T cells. We found that frequencies of specific CD8+T cell could be improved by multiplying epitope copies, while the MFI of IFN-γsecreted by epitope-specific CD8+T cells decreased synchronously. And further analysis showed that the decrease of MFI was not caused by the functional avidity variation of CD8+T cell receptor.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2150-2150
Author(s):  
Hong-jie Shen ◽  
Xin Ding ◽  
Jian-nong Cen ◽  
Yuan-yuan Wang ◽  
Xiao-fei Qi ◽  
...  

Abstract Abstract 2150 BMI1 is the most frequently altered PcG group protein observed in cancer and is useful in predicting prognosis as a biomarker in some malignant blood diseases including myelodysplastic syndromes (MDS) and chronic myelogenous leukemia (CML). However, the role and effect of BMI1 in these diseases is not clear. We have found that BMI1 expression in MDS CD34+ cells (n=13) was correlated with IPSS (R2=0.514,P=0.013). The MDS patient with overexpressed BMI1 shortly after diagnosis displayed a disease progression: one case of MDS-RA progressed to MDS-RAEB and two cases of MDS-RAEB transformed to AML, in company with more serious cytopenia in one or more lineages of bone marrow cells. A similar situation was found in CML. As the CML-CP patients (n=181) accelerated to CML-BP (n=27),the hemoglobin level as well as WBC and Plt counts markedly decreased (p<0.05), whereas the BMI1 transcriptional level in CML-BP (n=12) was much higher than that in CML-CP (n=26) detected by qRT-PCR (p<0.05). To further explore the role of BMI1 in malignant myeloid transformation, we cloned BMI1 cDNA ORF and transfected it into K562 by MSCV retroviral vector. The BMI1 protein expression in transfectant subclones was about three-folds of the untransfected control. NBT assay demonstrated that the differentiation induced by 20nm/L TPA for 72 hours in transfected cell were less than that in control cells. The percentage of NBT positive cells in K562, K562-MSCV, K562- BMI1SC1 and K562-BMI1SC2 were 51±7%, 60±8%, 27±6%, 33±7% (n=3), respectively. In addition, the immunophenotype of CD11b, CD13, CD15, CD33, CD34, CD64 and HLA-DR in TPA-treated cells detected by FCM found that only the mean fluorescence intensity of CD15 in transfected cells was obviously lower than that in control. The mean value of CD15 in K562, K562-MSCV, K562-BMI1SC1, K562-BMI1SC2 were 3.38, 3.25, 2.42, 2.54, respectively. The benzidine staining showed BMI1 transfected K562 treated by 40mm/L sodium butyrate for 72 hours had slower erythroid differentiation compared to that in control cells. The benzidine positive cell in K562, K562-MSCV, K562-BMI1SC1, K562-BMI1SC2 were 28±4%, 31±5%, 10±4%, 9±5% (n=3), respectively. We also found that the mean fluorescence intensity of GPA and CD71 were lower in BMI1 transfected cell compared to control after sodium butyrate treatment. The mean value of GPA in K562, K562-MSCV, K562-BMI1SC1, K562-BMI1SC2 were 36.4, 32.1, 20.6, 16.2 and the mean of CD71 were 3.07, 3.13, 2.8, 1.32, respectively. These in vitro results suggested that overexpression of BMI1 can inhibit cell myelomonocytoid and erythroid differentiation. In summary, we conclude that polycomb group BMI1 may contribute to clonal myeloid transformation by blocking multiple lineage differentiation and potentiating the stemness of the leukemia-initiating cells via possible epigenetic mechanisms. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 9 (2) ◽  
pp. 93-99
Author(s):  
Paula Kamińska ◽  
Karolina Buszka ◽  
Przemysław Pietras ◽  
Maciej Zabel ◽  
Michał Nowicki ◽  
...  

Abstract Immobilization of antibodies has a number of promising applications, including detection of biomolecules and cells. Well-oriented antibodies are required to bind them effectively. To eliminate the problem of random antibodies’ orientation, the surface of the device can be modified with silanes. This study aimed at elucidating if selected aminosilanes were able to bind antibodies in the appropriate orientation and thus retain their binding activity. Silanization of glass slides was performed using three amino-functional trialkoxysilanes – A, AE, and AEE. The immunofluorescent reaction was used to evaluate the potential of the silanized glass surface to bind anti-EpCAM antibodies. The affinity of selected anti-EpCAM HEA125 antibodies labeled with fluorochrome to tested silanized surfaces was evaluated by measuring the mean fluorescence intensity (MFI) in each analyzed area. The presented silanes effectively bound antibodies. Higher fluorescence intensity was noticed in the case of silane-coated glass slides in comparison to unmodified ones. The differences in the contact angles also confirmed this result. In the case of silane A, the fluorescence intensity reflected the amount of bound antibodies. However, there was no such a relation in the case of the silanes AE and AEE. Although our research gave promising results, the usefulness of selected silanes needs to be confirmed by further studies using cancer cells. Running title: Aminosilanes as enhancers of antibody immobilization


2021 ◽  
Vol 22 (15) ◽  
pp. 8256
Author(s):  
Adolfas K. Gaigalas ◽  
Yu-Zhong Zhang ◽  
Linhua Tian ◽  
Lili Wang

A stochastic model of the flow cytometer measurement process was developed to assess the nature of the observed coefficient of variation (CV%) of the mean fluorescence intensity (MFI) from a population of labeled microspheres (beads). Several sources of variability were considered: the total number of labels on a bead, the path through the laser beam, the optical absorption cross-section, the quantum yield, the numerical aperture of the collection optics, and the photoelectron conversion efficiency of the photomultiplier (PMT) cathode. The variation in the number of labels on a bead had the largest effect on the CV% of the MFI of the bead population. The variation in the path of the bead through the laser beam was minimized using flat-top lasers. The variability in the average optical properties of the labels was of minor importance for beads with sufficiently large number of labels. The application of the bead results to the measured CV% of labeled B cells indicated that the measured CV% was a reliable measure of the variability of antibodies bound per cell. With some modifications, the model can be extended to multicolor flow cytometers and to the study of CV% from cells with low fluorescence signal.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 300
Author(s):  
Petr Kelbich ◽  
Aleš Hejčl ◽  
Jan Krejsek ◽  
Tomáš Radovnický ◽  
Inka Matuchová ◽  
...  

Extravasation of blood in the central nervous system (CNS) represents a very strong damaged associated molecular patterns (DAMP) which is followed by rapid inflammation and can participate in worse outcome of patients. We analyzed cerebrospinal fluid (CSF) from 139 patients after the CNS hemorrhage. We compared 109 survivors (Glasgow Outcome Score (GOS) 5-3) and 30 patients with poor outcomes (GOS 2-1). Statistical evaluations were performed using the Wilcoxon signed-rank test and the Mann–Whitney U test. Almost the same numbers of erythrocytes in both subgroups appeared in days 0–3 (p = 0.927) and a significant increase in patients with GOS 2-1 in days 7–10 after the hemorrhage (p = 0.004) revealed persistence of extravascular blood in the CNS as an adverse factor. We assess 43.3% of patients with GOS 2-1 and only 27.5% of patients with GOS 5-3 with low values of the coefficient of energy balance (KEB < 15.0) in days 0–3 after the hemorrhage as a trend to immediate intensive inflammation in the CNS of patients with poor outcomes. We consider significantly higher concentration of total protein of patients with GOS 2-1 in days 0–3 after hemorrhage (p = 0.008) as the evidence of immediate simultaneously manifested intensive inflammation, swelling of the brain and elevation of intracranial pressure.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1161
Author(s):  
Lidia Delrieu ◽  
Liacine Bouaoun ◽  
Douae El Fatouhi ◽  
Elise Dumas ◽  
Anne-Deborah Bouhnik ◽  
...  

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey “vie après cancer” VICAN (January–June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue (p = 0.03) and an increase in cognitive sequelae was reported (p = 0.03). Two latent classes were identified—functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.


Author(s):  
Yong Sul Won ◽  
Jong-Hoon Kim ◽  
Chi Young Ahn ◽  
Hyojung Lee

While the coronavirus disease 2019 (COVID-19) outbreak has been ongoing in Korea since January 2020, there were limited transmissions during the early stages of the outbreak. In the present study, we aimed to provide a statistical characterization of COVID-19 transmissions that led to this small outbreak. We collated the individual data of the first 28 confirmed cases reported from 20 January to 10 February 2020. We estimated key epidemiological parameters such as reporting delay (i.e., time from symptom onset to confirmation), incubation period, and serial interval by fitting probability distributions to the data based on the maximum likelihood estimation. We also estimated the basic reproduction number (R0) using the renewal equation, which allows for the transmissibility to differ between imported and locally transmitted cases. There were 16 imported and 12 locally transmitted cases, and secondary transmissions per case were higher for the imported cases than the locally transmitted cases (nine vs. three cases). The mean reporting delays were estimated to be 6.76 days (95% CI: 4.53, 9.28) and 2.57 days (95% CI: 1.57, 4.23) for imported and locally transmitted cases, respectively. The mean incubation period was estimated to be 5.53 days (95% CI: 3.98, 8.09) and was shorter than the mean serial interval of 6.45 days (95% CI: 4.32, 9.65). The R0 was estimated to be 0.40 (95% CI: 0.16, 0.99), accounting for the local and imported cases. The fewer secondary cases and shorter reporting delays for the locally transmitted cases suggest that contact tracing of imported cases was effective at reducing further transmissions, which helped to keep R0 below one and the overall transmissions small.


1982 ◽  
Vol 14 (1) ◽  
pp. 7-16 ◽  
Author(s):  
M. A. Khalifa

SummaryIn a survey of 1475 urban Moslem wives in the age group 15–49 living in the capital city of the Sudan, knowledge of birth control was reported by almost all respondents while a significant proportion had used contraception at least once. The mean age of the users was 32·8 years, their duration of marriage was 15·1 years and their mean number of surviving children was 4·6. Those who had never used contraception had a higher mean age, a longer duration of marriage and more surviving children. Most of the users had an urban residential background and belonged to the high socioeconomic class. They held favourable attitudes to family planning. Although they thought that having a large family (more than five children) was not desirable, their mean preferred family size was no different from that of the never users.The results indicate that contraception is used for the purpose of spacing births rather than limiting their ultimate number. At this early stage of contraceptive adoption in Sudan, the characteristics of the pioneer acceptors are similar to those observed in other African countries.


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