High Proportion Of Eosinophils Research Articles

Morphological Features and Morphometric Parameters of Peripheral Blood Eosinophiles in Raccoon Dogs <i>Nyctereutes procyonoides</i> (Grey, 1834)

The aim of this work was to analyze the morphology and morphometric parameters of peripheral blood eosinophils and eosinophilic granules in raccoon dogs Nyctereutes procyonoides (Grey, 1834). On blood smears stained by Pappenheim, the composition of the leukocyte formula was determined, the morphological features and morphometric parameters of eosinophils and their granules were evaluated. Cytochemical methods revealed the localization of peroxidase and cationic proteins in eosinophils. ANOVA was used to assess the effect of sex. As a result of the study, it was found that raccoon dogs are characterized by a high relative content of eosinophils (7–10%), as well as the presence of large secretory granules in them. Along with the common eosinophils, there were cells with abnormal granularity (low number of secretory granules, the presence of vacuole-like granules that did not stain with the dyes used). The influence of sex was expressed in a higher proportion of eosinophils with abnormal granularity in males compared to females, while the latter had higher morphometric parameters (the number and average area of granules in one cell, the ratio of the area occupied by granules to the area of the cell). Since the causes of abnormally granular eosinophils in raccoon dogs are not completely clear, there is a need for further research into this issue.

Bioinformatics analysis reveals the landscape of immune cell infiltration and novel immune-related biomarkers in moyamoya disease.

Objective: This study aimed to identify immune infiltration characteristics and new immunological diagnostic biomarkers in the cerebrovascular tissue of moyamoya disease (MMD) using bioinformatics analysis. Methods: GSE189993 and GSE141022 were downloaded from the GEO database. Differentially expressed gene and PPI analysis were performed. After performing WGCNA, the most significant module associated with MMD was obtained. Next, functional pathways according to GSEA, GO, and KEGG were enriched for the aforementioned core genes obtained from PPI and WGCNA. Additionally, immune infiltration, using the CIBERSORT deconvolution algorithm, immune-related biomarkers, and the relationship between these genes, was further explored. Finally, diagnostic accuracy was verified with ROC curves in the validation dataset GSE157628. Results: A total of 348 DEGs were screened, including 89 downregulated and 259 upregulated genes. The thistlel module was detected as the most significant module associated with MMD. Functional analysis of the core genes was chiefly involved in the immune response, immune system process, protein tyrosine kinase activity, secretory granule, and so on. Among 13 immune-related overlapping genes, 4 genes (BTK, FGR, PTPN11, and SYK) were identified as potential diagnostic biomarkers, where PTPN11 showed the highest specificity and sensitivity. Meanwhile, a higher proportion of eosinophils, not T cells or B cells, was demonstrated in the specific immune infiltration landscape of MMD. Conclusion: Immune activities and immune cells were actively involved in the progression of MMD. BTK, FGR, PTPN11, and SYK were identified as potential immune diagnostic biomarkers. These immune-related genes and cells may provide novel insights for immunotherapy in the future.

Clinical Significance of Angiographically Detectable Neovascularity in Patients with Cardiac Myxoma

Background: Myxomas are the most common primary cardiac tumors. Angiographically detectable neovascularity (ADN) of myxoma is increasingly being reported as a result of the use of coronary angiography (CAG) to detect coronary artery disease. However, the clinical significance of these findings is not fully understood. Methods: We enrolled 59 patients with cardiac myxoma who also underwent CAG between January 2013 and October 2018. Patients were followed up for a mean of 28.9 months (range 1–69 months). The clinical features, echocardiography measurements, pathological examination findings, CAG results, and outcomes during follow-up were compared between patients with ADN and patients without ADN. Results: ADN was found in 25 patients (42.4%). The arteries feeding the ADN included the right coronary artery (n=15), the left circumflex coronary artery (n=7), and both arteries (n=3). The patients with ADN had a higher proportion of eosinophils (3.2% vs. 2.2%, P=0.03) and higher low-density lipoprotein cholesterol level (2.7 mmol/L vs. 2.2 mmol/L, P=0.02). Myxoma pedicles were more likely to be located in the interatrial septum in patients with ADN (96% vs. 73.5%, P=0.02). No significant correlation was observed between the groups in clinical manifestations, atrial arrhythmia, myxoma size, cardiac chamber size, left ventricular ejection fraction, and the prevalence of complication with coronary artery disease [16% in the ADN group (n=4) vs. 20.6% in the non-ADN group (n=7), P=0.66]. However, patients with ADN tended to have a lower incidence of major adverse cardiac and cerebrovascular events on long-term follow-up (0% vs. 14.7%, P=0.07). Conclusion: CAG-detected ADN in patients with cardiac myxoma is associated with a borderline lower rate of major adverse cardiac and cerebrovascular events.

Abstract TMEM-037: GENE EXPRESSION ANALYSIS IDENTIFIES IMMUNOLOGICAL MRNA UP REGULATION IN CELLS IN THE ASCITES OF SEROUS OVARIAN CANCER AS COMPARED TO MATCHED PRIMARY TUMOR

Abstract BACKGROUND: Ovarian cancer patients with advanced disease frequently develop ascites. It is currently unclear to what extent the molecular phenotype of the cells in ascites differs from that of the primary ovarian tumor. There is also speculation that the tumor cells in ascites may represent a more treatment resistant cell population. An improved understanding of the biology of the cellular environment in ovarian cancer-related ascites may reveal opportunities to develop new targeted therapies that may not be apparent through analysis of the primary tumor alone. The aim of the study was to evaluate potential biological differences between the cellular environment of primary ovarian tumors and that of the ascites fluid. METHODS: We performed mRNA expression in n=12 matched pairs of primary serous OVCA tumor and the cellular component of ascites using the HTG Edge System and the EdgeSeq Oncology Biomarker Panel assay. After normalization, log expression values for 2650 genes were compared between tumor and ascites samples using principle component analysis (PCA) modeling. The molecular profiles of primary tumor and ascites were compared using a t-test. Additionally, the CiberSort algorithm was applied to estimate the relative composition of tumor infiltrating lymphocytes in tumor and ascites samples. RESULTS: PCA modeling demonstrated a clear difference between the primary tumor and ascites samples using all genes. A group comparison (q<0.01, FDR corrected p-value, fold change >2) indicated that 49 genes were differentially expressed between primary tumor and ascites samples. Ascites samples showed significantly higher expression of T-cell markers, CD2, CD3D, CD4, and CD8A, as well as the monocyte/macrophage markers CD14, CCL4, CD163, CCR1, IL10, and ITGAM. CiberSort analysis revealed a high proportion of eosinophils (p <2 x 10^-7) and monocytes (p<0.0002) in ascites as compared to tumor while resting mast cells were proportionately greater in the tumor samples (p < 4 x 10^-5). CONCLUSIONS: In this study, we report a significant difference in mRNA expression between primary tumors from serous OVCA and ascites. Ascites samples were found to have higher expression of T cell, monocyte and macrophage mRNA. Interestingly, ascites samples also expressed an increased proportion of eosinophils as compared to primary tumor. Eosinophils have been suggested to be essential for CD8+ T-cell mediated tumor rejection and have been associated with improved outcomes in prognosis. We also report an increased proportion of resting mast cells in primary tumor. Mast cells are increasingly thought to play a role in the regulation of tumor growth. In summary, this study demonstrates that molecular profile of cells in ascites is different than that of primary tumor and that this difference is potentially due to immune modulators. Citation Format: Sharon E. Robertson, MD, MPH, Douglas C. Marchion, PhD, Yin Xiong, PhD, Anders E. Berglund, PhD, Anthony M. Magliocco, MD. GENE EXPRESSION ANALYSIS IDENTIFIES IMMUNOLOGICAL MRNA UP REGULATION IN CELLS IN THE ASCITES OF SEROUS OVARIAN CANCER AS COMPARED TO MATCHED PRIMARY TUMOR [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-037.

A 67-Year-Old Patient with Severe Generalized Oedema

We report a case of a 67-year-old Caucasian man who was admitted to the emergency department with severe and generalized oedema accompanied by a rash of both lower legs. The patient was treated with loop diuretics throughout four months without success. Laboratory examinations displayed a leukocytosis with a high proportion of eosinophils. A comprehensive diagnostic work up was started. Finally, a full-thickness skin biopsy including fascia showed eosinophilic infiltration suitable for an eosinophilic fasciitis. Briefly after starting a glucocorticoid therapy the patient lost 10 kg on body weight, the generalized oedema resolved.

Histamine‐treated dendritic cells improve recruitment of type 2 CD8 T cells in the lungs of allergic mice

Histamine controls the function of dendritic cells (DCs). It appears to be required for the normal development of DCs. It also induces the chemotaxis of immature DCs and promotes the differentiation of CD4(+) T cells into cells with a T helper type 2 (Th2) profile. Moreover, we have recently shown that histamine stimulates both the uptake and the cross-presentation of antigens by DCs, supporting the theory that histamine promotes activation of CD8(+) T cells during the development of allergic pathologies. Here, we investigated whether the course of an allergic response, in a well-defined model of ovalbumin (OVA)-induced allergic airway inflammation, could be modulated by intratracheal injection of OVA-pulsed DCs previously treated with histamine (DCHISs). Compared with control DCs, DCHISs induced: (i) greater recruitment of CD8(+) T cells in the lung, (ii) greater stimulation of the production of interleukin (IL)-5 by lung CD8(+) T cells, and (iii) increased recruitment of CD11c/CD8 double-positive DCs in the lungs of allergic mice. Moreover, mice treated with DCHISs showed increased levels of serum-specific immunoglobulin E (IgE) antibodies directed to OVA, and a higher proportion of eosinophils in bronchoalveolar lavage (BAL) compared with mice treated with OVA-pulsed control DCs. Our results support the notion that histamine, by acting on DCs, increases the severity of allergic processes.

How Viral Infections Cause Exacerbation of Airway Diseases

Exacerbations of asthma and COPD are major causes of morbidity, mortality, and health-care costs. Over the last decade, studies using new molecular diagnostic techniques have established that respiratory viruses are a major cause of exacerbations of both asthma and COPD. The most prevalent viruses detected during exacerbations are the rhinoviruses. Despite the burden of disease associated with exacerbations, little is known about the mechanisms of virus-induced exacerbations of airway diseases. Exacerbations are associated with increased airway inflammation in patients with both asthma and COPD, but many questions remain unanswered regarding the key inflammatory cells and mediators involved. Identifying the key inflammatory mediators involved in exacerbations holds the promise of developing diagnostic and prognostic markers of exacerbation. In addition, such studies can identify new therapeutic targets for the development of novel drugs for the prevention and treatment of exacerbations.

Acquired cervical scoliosis attributed to Parelaphostrongylus tenuis infection in an alpaca

A 2-year-old alpaca was evaluated because of acute onset of cervical scoliosis. Physical examination revealed severe scoliosis of the caudal portion of the cervical vertebral column with a C-shaped curvature to the right side. No gait deficits were observed. Cervical radiography confirmed severe curvature of C4 to C6 but did not reveal any bony changes. Cerebrospinal fluid had high total protein concentration and extremely high nucleated cell count with a high proportion of eosinophils, suggesting parasitic infection. The alpaca was treated for suspected parelaphostrongylosis with ivermectin, fenbendazole, flunixin, vitamin E, thiamine, physical therapy, and a custom-made neck brace. The alpaca's condition continued to deteriorate, and it developed tetraparesis and ataxia and was euthanized after approximately 1 month. Microscopic evaluation of the cervical spinal cord revealed marked vacuolar changes in the left medial portion of the ventral funiculus, mild lymphoplasmacytic infiltration, and multifocal granulomas. The lesions were continuous from C1 to C7 and were compatible with parasite migration. To the authors' knowledge, this is the first report of acquired scoliosis in an alpaca, which appears to represent an unusual manifestation of parelaphostrongylosis that was reported in horses.

Nitric Oxide Metabolites, Eosinophils and Eosinophilic Cationic Protein in Patients with Asthma: Sputum versus Blood

The monitoring of airway inflammation has assessed in bronchial asthma directly by sputum examination, and indirectly by measurements in peripheral blood. To investigate the diagnostic value of these two methods, we compared nitric oxide (NO) metabolites, eosinophils, and eosinophil cationic protein (ECP) in sputum and blood in patients with asthma and control subjects. Sputum and serum were obtained from fifteen patients with asthma, and then were examined before anti-asthma treatment, including steroid preparations. ECP was measured by fluoroimmunoassay. NO metabolites were assayed by using modified Griess reaction. Asthmatic patients, compared with control subjects, had significantly higher level of NO metabolites, higher proportion of eosinophils, and higher levels of ECP in sputum. Asthmatic patients, compared with control subjects, however, had significantly higher number of eosinophils, and were at higher levels of ECP in blood. FEV1, FEV1/FVC was negatively correlated with sputum eosinophils. The area under receiver operating characteristic (ROC) curve showed that eosinophils in sputum are significantly accurate markers than NO metabolites in sputum and blood. These findings suggest that the proportion of eosinophils in sputum have more accurate diagnostic marker of asthmatic airway inflammation than NO metabolites in sputum in differentiating asthmatic patients from control subjects.

Effects of prednisolone on eosinophils, IL-5, eosinophil cationic protein, EG2+ eosinophils, and nitric oxide metabolites in the sputum of patients with exacerbated asthma

Corticosteroids are considered to be one of the most effective medicine for asthma by suppressing airway inflammation. This study was carried out to investigate the effects of prednisolone in the sputum of exacerbated asthmatics. Clinical severity, cell differentials, levels of interleukin (IL)-5, eosinophil cationic protein (ECP), EG2+ eosinophils, and nitric oxide (NO) metabolites were measured. Sputum was examined 2 weeks apart in 13 exacerbated asthmatics before and after prednisolone treatment, and once in 12 stable asthmatics. We used a sandwich ELISA for IL-5, fluoroimmunoassay for ECP, immunohistochemical staining for EG2+ eosinophils, a NO metabolites assay using modified Griess reaction. Exacerbated asthmatics, in comparison with stable asthmatics, had significantly higher proportion of eosinophils, higher level of ECP, higher percentage of EG2+ eosinophils, and NO metabolites. Exacerbated asthmatics after treatment with prednisolone had reduced the proportions of eosinophils, reduced level of IL-5, ECP and percentage of EG2+ eosinophils. FEV1 was correlated with the proportion of eosinophils, ECP, and IL-5 respectively. These findings suggest that prednisolone is considered to be effective medicine for asthma by suppressing eosinophil activation through IL-5.

Pneumocystis carinii Pneumonia in Human Immunodeficiency Virus (HIV)—Positive and HIV-Negative Immunocompromised Patients

For 89 human immunodeficiency virus (HIV)-positive and 32 HIV-negative immunocompromised patients who had 121 episodes of Pneumocystis carinii pneumonia (PCP), clinical features and changes over time were compared. HIV-infected patients characteristically had a longer duration of symptoms (23 vs. 13 days; P<.005); were younger (39 vs. 48 years; P<.001); had a higher frequency of sweating, weight loss, and thoracic pain; and had fewer admissions to the intensive care unit (16% vs. 31%; P<.05). In addition, they had significantly higher hemoglobin levels, lower thrombocyte counts, lower C-reactive protein values, and a higher proportion of eosinophils and lymphocytes in bronchoalveolar lavage fluid. After 1995, HIV-negative patients' mean length of stay dropped from 34 days to 16 days (P<.005), and their hospital mortality rate dropped from 29% to 7% (P<.001). HIV-positive patients with PCP differed in several aspects from those without HIV infection. Knowledge gained from experience with treatment of opportunistic infections in patients with AIDS has improved the management of PCP in patients with other immunodeficiencies.

In the absence of IL-12, the induction of Th1-mediated protective immunity by the attenuated schistosome vaccine is impaired, revealing an alternative pathway with Th2-type characteristics.

Vaccination of mice with irradiated Schistosoma mansoni larvae confers high levels of immunity which is mediated by Th1-type lymphocytes. To investigate a possible role for IL-12 in the induction of protection, we have compared the immune response of IL-12 p40-deficient (KO) mice and their C57BL/6 (WT) counterparts following vaccination. Cultured lymph node cells from KO mice had markedly altered cytokine profiles with significantly decreased production of IFN-gamma increased IL-4. Correspondingly, KO mice had enhanced levels of IgE. After challenge, cells recovered from the lungs of KO mice secreted abundant IL-4 and IL-5 but little IFN-gamma, while flow cytometric and histological analysis of lung cell populations recorded a very high proportion of eosinophils. The levels of protection in KO mice were substantially lower than in their WT counterparts, demonstrating the importance of IL-12 and Th1-mediated immune responses. This conclusion is reinforced by the administration of rIL-12 to KO mice immediately after vaccination which led to increased IFN-gamma and the restoration of protective immunity. Nevertheless, the data also indicated that the limited levels of protection induced in KO mice occur via an IL-12-independent pathway, possibly mediated by Th2 cells.

Lung immunopathology in cases of sudden asthma death.

The histopathology of airway inflammation in rare cases of sudden asphyxic asthma death (SAAD) is unclear. This study examines, for the first time, the relative disposition of lymphocyte and macrophage subsets and eosinophils in proximal and distal tissues of such cases. Multiple resection specimens from five cases of SAAD were studied. Tissue blocks were obtained at necroscopy and immediately frozen in liquid nitrogen within 18 hours of death (death occurring within 1 h of the onset of an unprovoked asphyxic asthma attack). After immunohistological staining, frozen sections underwent semi-quantitative analysis (cell counts per unit area) for T-cells, macrophages and eosinophils using computerized imaging systems. Subsets of T-cells and macrophages were estimated using double immunofluorescence techniques. Variability within samples, between samples and between cases was compared. These cases of fatal asthma showed infiltrates of T-cells, macrophages and eosinophils within peribronchial tissues. Distinct from stable asthma, a CD8+ T-cell dominance was found. A high proportion of eosinophils were activated (EG2+), whereas the relative proportion of antigen-presenting cells (RFD1+) did not seem to be abnormal, although numbers of these cells were high. These features were seen both in proximal and distal tissues. The variability of these parameters within an individual was 9.4-15.2%, however, the variability between individual cases was greater. Sudden asphyxic asthma is associated with inflammatory infiltrates both of proximal and distal lung tissues. In contrast to stable asthma, this infiltrate contains large numbers of CD8+ T-cells, suggesting distinct qualitative as well as quantitative characteristics in the immunopathology of sudden asthma death.

The effects of perennial allergic rhinitis on dental and skeletal development: A comparison of sibling pairs

This study analyzed the effect of perennial allergic rhinitis on dental and facial skeletal characteristics. Twenty-five allergic children who were apparent mouth breathers, their 25 siblings who did not have the disease and were apparent nose breathers, and 14 nasal breathing control subjects were examined medically, dentally, and cephalometrically. Compared with their siblings, the allergic subjects had more nasal mucosal edema, a higher proportion of eosinophils in their nasal secretions, and greater nasal power. The allergic subjects were characterized by deeper palatal height, retroclined mandibular incisors, increased total anterior facial height and lower facial height, a larger gonial angle, and greater SN, palatal, and occlusal planes to mandibular plane angles. All of these measures except gonial angle were also significantly different between the allergic children and the nonconsanguineous controls. Also, the allergic subjects compared with controls had smaller SNB and SN-pogonion angles and an increased overjet. Both allergic and nonallergic sibling groups showed larger mean adenoid size on radiographs than controls. For most variables the nonallergic siblings fell between the allergic children and the control subjects. Overall, the allergic children had longer, more retrusive faces than controls. This retrusive characteristic was present in nonallergic siblings and cannot be ascribed to the apparent breathing mode at the time of the study. These results confirm earlier reports that allergic rhinitis may be associated with altered facial growth. Controlled longitudinal studies to analyze a possible cause-and-effect relationship and the effects of medical and surgical treatments should be undertaken.