IL-1R8 expression in DLBCL regulates NK cell recruitment and influences patient prognosis.

The precise biological function of Interleukin-1 receptor 8 (IL-1R8) in diffuse large B-cell lymphoma (DLBCL) is still not well understood. Our goal is to decipher the profile of IL-1R8 expression status in DLBCL and to explore how IL-1R8 is involved in DLBCL progression. Utilizing a tissue microarray consisting of 70 samples of DLBCL tumors alongside 15 samples of tonsillitis, our investigation revealed a parallel expression profile of IL-1R8 between the tumor tissues and tonsillitis samples (p > 0.05). Nevertheless, an intriguing association emerged, as heightened expression of IL-1R8 correlated significantly with unfavorable survival outcomes in patients with DLBCL (p < 0.05). The status of IL-1R8 expression did not directly regulate proliferation (p > 0.05) and apoptosis (p > 0.05) in DLBCL cells via CCK8 and apoptotic assays. Subsequent chemotaxis analysis indicated that natural killer (NK) cell recruitment could be suppressed by IL-1R8 signaling in DLBCL, at least partially through CXCL1 inhibition (p < 0.05). The status of IL-1R8 expression in tumor tissues exhibited a negative correlation with the density of CD57+ NK cell infiltration (p < 0.05), while it did not demonstrate a significant association with CD3+ T cells (p > 0.05), CD68+ macrophages (p > 0.05), or S-100+ dendritic cells (p > 0.05). In line with this observation, elevated levels of NK cell infiltration demonstrated a significant positive correlation with improved overall survival (OS) among patients diagnosed with DLBCL (p < 0.05). Our data suggests the immuno-regulating potential of IL-1R8 through NK cell recruitment in DLBCL, providing novel insights into future immuno-modulating therapies.

ANTIBODIES TO MICROBIAL ANTIGENS AND CYTOKINES IN THE CELLS OF THE PALATINE TONSILS AND SERUM OF CHILDREN WITH PALATINE TONSILS HYPERTROPHY AND CHRONIC TONSILLITIS.

OBJECTIVE: The aim: The aim of the study is to compare the class G antibody content in serum and tissue lysate from tonsils of children with hypertrophy and chronic tonsillitis to: streptolysin-O of Str. haemolyticus, protein-A of S. aureus, proteoglycans of Klebsiela spp., as well as to compare the content of interleukins 1ß, 10, TNF-α, γ-IFN and lactoferrin in serum and tissue lysate from tonsils of children with hypertrophy and chronic tonsillitis. PATIENTS AND METHODS: Materials and methods: We studied tonsils of 33 children aged 4-18 years with hypertrophy of palatine tonsils (HPT) and with chronic tonsillitis (CT). The content of interleukins 1ß, 10, TNF-α, γ-IFN and lactoferrin in tonsil lysate and serum was determined by immunofluorescence assay. Antistreptolysin O was studied by neutralization test of micromethod; class G antibodies to protein A of S. aureus and proteoglycans of Klebsiela spp. were studied by treponema pallidum hemagglutination assay. All the results were statistically processed using U-test (Mann-Whitney-Wilcoxon test) and Fisher's z-transformation. RESULTS: Results: The serum and tissue lysate from tonsils of patients with HPT showed significantly high level of antibodies to streptolysin O in comparison with similar studies of substrates from patients with CT. Anti-inflammatory cytokine IL-10 was detected only in the serum of patients with CT. The TNF-α concentration in the lysates of tonsils in the group of patients with HPT was 2 times higher than in the group of patients with CT. The γ-IFN concentration was significantly lower both in the serum and in the lysates of tonsils of patients with CT. The content of lactoferrin in the lysates of patients with CT was 3 times higher (P<0.05) than in the lysates of patients with HPT. CONCLUSION: Conclusions: The results indicate a significant difference in the state of antibodies to microbial antigens and cytokines production in case of HPT and CT. In tonsils with HPT, there predominate reactions of antibody production to bacterial antigens and antiviral reactions like a high-level cytokines TNF-α and γ-IFN in tissue lysate of palatine tonsils.

Interaction between Ras and Bcl2L12 in B cells suppresses IL-10 expression.

The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.

Deciphering the fate of slan+ -monocytes in human tonsils by gene expression profiling.

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study.

OBJECTIVES: Tonsil tissue is a very important component of the human immunity system, contributing to the functioning of the cellular and humoral defence system, especially in childhood. The endoplasmic reticulum (ER) is an organelle that has a very important function in the balanced functioning of cells, in which the accumulation of a cellular protein called ER stress occurs in case of dysfunction. ER stress influences the pathogenesis of many diseases and immune system functions. We aimed to investigate the relation between the diseases of tonsil tissue and ER stress response to elucidate the mechanisms of diseases related with the immune system. METHODS: A prospective study was conducted in 46 children aged between 2 and 16 years who underwent tonsillectomy for chronic tonsillitis or tonsillar hypertrophy. Tonsil tissue was separated into two groups according to their size and evaluated in terms of ER stress markers and apoptosis markers by Real-time PCR and Western blot analysis. RESULTS: The ΔCT levels of ER stress markers (ATF4, ATF6, CHOP, GRP78, EIF2AK3, ERN1, GRP94) were greater in children with chronic tonsillitis (p < 0.005). In contrast, the tonsillar hypertrophy group had greater ΔCT levels of apoptosis markers (BAX, BCL-2) according to the Real-time PCR method (p < 0.005). According to the Western blot analysis, the normalized levels of ATF4, ATF6, CHOP, GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group. There was no difference between the two groups in terms of normalized BCL-2 and BAX levels by Western blot analysis. CONCLUSION: This is the first study in the literature investigating the effect of the ER stress pathway on the etiopathogenesis of tonsil diseases. It was concluded that the ER stress pathway plays a role in the etiopathogenesis of chronic tonsillitis. Investigating the relationship between ER stress and structures such as the tonsil tissue that make up the immune system can help create new treatment strategies. CLINICAL TRIAL REGISTRATION: Trial Registration ClinicalTrials.gov Identifier: NCT04653376.

Prevalence of humoral immunodeficiency in adult patients with recurrent tonsillitis.

PURPOSE: Recurrent tonsillitis in adults has a significant impact on patients' daily life and healthcare costs. Humoral immunodeficiency increases the susceptibility to recurrent infections. The purpose of this study was to investigate the prevalence and contribution of humoral immunodeficiency in adult patients with recurrent tonsillitis. MATERIAL AND METHODS: A prospective cross-sectional study conducted over 3 years duration with two groups of subjects. Group 1: included 50 normal adult subjects and group 2: included 50 adult patients with recurrent tonsillitis. Recruitment occurred in a tertiary care hospital in Egypt. Different immunoglobulins (Ig A, Ig M and Ig G isotypes) were quantitatively assessed and compared in 2 groups. Incidence of different infections was also compared in patients with humoral immunodeficiency versus patients with intact immunity. RESULTS: 4 (8%) subjects in group 1 had selective humoral Immunodeficiency versus 13 (26%) patients in group 2. Patients with recurrent tonsillitis had significantly lower mean of most assessed immunoglobulins: IgA (P = 0.002), IgM (P = 0.003), IgG (P < 0.0001), IgG1 (P < 0.0001) and IgG3 (P < 0.0001) compared to normal subjects; with no significant difference in mean of IgG2 (P = 0.395) and IgG4 (P = 0.105). Patients with humoral immunodeficiency had significantly higher incidence of tonsillitis (P < 0.0001) and rhinosinusitis (P < 0.0001) attacks compared to patients with normal immunity. CONCLUSION: Adult patients with recurrent tonsillitis may have higher prevalence of humoral immunodeficiency compared to normal subjects. These findings suggest that assessment of immune function should be undertaken routinely in these patients.

[Proinflammatory cytokine content in the saliva of children suffering from chronic tonsillitis]. / Soderzhanie provospalitel'nykh tsitokinov v sliune detei s khronicheskim tonzillitom.

INTRODUCTION: We have examined 92 children aged between 6 and 15, suffering from chronic tonsillitis (CT). Tumor necrosis factor (TNF-α) and interleukin 1ß and 6 (IL-1ß and IL-6) contents have been defined in saliva. The control set comprised 17 healthy children. Cytokine content was defined with the enzyme multiplied immunoassay sets (Vektor Best Ltd., Russia) by enzyme-linked immunosorbent assay. The statistic analysis and data processing were carried out with statistic analysis programs (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: The content of cytokines TNF-α, IL-1, IL-6 in CT children's saliva was high against the healthy children, yet the statistically significant differences were only noted for IL-6. In the CT group the median value of this factor (12.5) was significantly higher than in the control set (6.72) (p=0.01 in Mann-Whitney assessment). IL-6 was chosen as the basic factor for the mathematic model; its combinations in the form of a multi-factor logistic regression were given consideration. From out of the three possible models there was just one that had all the coefficients statistically significantly different from zero (TNF-α - IL-6). It was chosen as the basic diagnostic model for chronic tonsillitis. The created model's sensitivity is 80.4%, while its specificity is 82.4%. DISCUSSION: The revealed IL-6 dominance in saliva at CT can be is attributable to permanent antigenic challenge characteristic of the toxic allergic CT since, as previously shown, there are living proliferating microorganisms in the palatal tonsil tissues and their blood- and lymph vessels at CT. CONCLUSION: The conducted ROC-analysis has demonstrated high sensitivity and specificity of the mathematical model, which enabled us to recommend determination of IL-6 in the saliva of the children suffering from CT as an additional diagnostic criterion.

DYNAMICS OF CONTENT OF SOME MINERALS IN TEENAGERS WITH CARDIOVASCULAR SYSTEM PATHOLOGY AGAINST THE BACKGROUND OF CHRONIC TONSILLITIS ZMIANY ZAWARTOSCI NIEKTÓRYCH SKLADNIKÓW MINERALNYCH U MLODZIEZY Z CHOROBAMI UKLADU SERCOWO-NACZYNIOWEGO JAKO PODLOZE ROZWOJU PRZEWLEKLEGO ZAPALENIA MIGDALKÓW PODNIEBIENNYCH.

OBJECTIVE: Introduction: Chronic diseases of the upper respiratory tract in children and teenagers, such as chronic tonsillitis is quite common in pediatric populations, accompanied by changes in reactivity, causing a risk of complications. Due to the fact that the child's body resistance to acute infectious diseases depends on the sufficiency of trace elements, then at present stage greatly increased interest in deeper study of exchange of macro- and microelements in the human body in normal and pathological conditions. The aim: To study the dynamics of zinc, iron, potassium and magnesium in adolescents with disorders of the cardiovascular system with chronic tonsillitis. PATIENTS AND METHODS: Materials and methods: It was examined 63 patients with chronic tonsillitis, among them- 31 children suffer from chronic tonsillitis off-damage to the cardiovascular system (I group), 32 patients with disorders of the cardiovascular system against the background of chronic tonsillitis (II group). The content of trace elements zinc, iron, minerals potassium and magnesium was analyzed. The measurement and calculation were done according to AAS-SPECTR program. Analysis and statistics treatment was done on using application programs STATISTICA 7.0 and MS Excel XP. RESULTS: Results: In result of investigation it was found a violation of trace element composition in the blood serum. Thus, in patients with chronic tonsillitis without cardiovascular system damage during hospitalization was observed a significant decrease in the concentration of iron to (15,47 ± 1,12) mmol/l. Similar changes were observed with the concentration of zinc in the blood serum. In patients with chronic tonsillitis without cardiovascular system damage during hospitalization was observed a significant decrease in the concentration of iron to (15,47 ± 1,12) mmol/l. Similar changes were observed with the concentration of zinc in the blood serum of patients of I groups during hospitalization (10,89 ± 0,57mmol/l) and was significantly lower compared with the data of healthy children (18,40 ± 0,71 mmol/l (p <0.05)). CONCLUSION: Сonclusions: It should be noted that children with tonsillogene cardiac lesions during hospitalization have a significant decreasing in the level of magnesium compared with indicators of children without pathology of the cardiovascular system. After treatment, the normalization of trace elements iron, zinc, magnesium did not happen, moreover, significant changes were observed in patients with heart disease against the background of chronic tonsillitis.

Infection biomarkers in primary care patients with acute respiratory tract infections-comparison of Procalcitonin and C-reactive protein.

BACKGROUND: There is a lack of studies comparing the utility of C-reactive protein (CRP) with Procalcitonin (PCT) for the management of patients with acute respiratory tract infections (ARI) in primary care. Our aim was to study the correlation between these markers and to compare their predictive accuracy in regard to clinical outcome prediction. METHODS: This is a secondary analysis using clinical and biomarker data of 458 primary care patients with pneumonic and non-pneumonic ARI. We used correlation statistics (spearman's rank test) and multivariable regression models to assess association of markers with adverse outcome, namely days with restricted activities and persistence of discomfort from infection at day 14. RESULTS: At baseline, CRP and PCT did not correlate well in the overall population (r(2) = 0.16) and particularly in the subgroup of patients with non-pneumonic ARI (r(2) = 0.08). Low correlation of biomarkers were also found when comparing cut-off ranges, day seven levels or changes from baseline to day seven. High baseline levels of CRP (>100 mg/dL, regression coefficient 1.6, 95 % CI 0.5 to 2.6, sociodemographic-adjusted model) as well as PCT (>0.5ug/L regression coefficient 2.0, 95 % CI 0.0 to 4.0, sociodemographic-adjusted model) were significantly associated with larger number of days with restricted activities. There were no associations of either biomarker with persistence of discomfort at day 14. CONCLUSIONS: CRP and PCT levels do not well correlate, but both have moderate prognostic accuracy in primary care patients with ARI to predict clinical outcomes. The low correlation between the two biomarkers calls for interventional research comparing these markers head to head in regard to their ability to guide antibiotic decisions. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN73182671.

Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients with chronic tonsillitis.

To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has important roles in the differentiation of lymphoid cells, and oxidative stress in patients with chronic tonsillitis. Serum and tissue samples were obtained from 25 patients who underwent tonsillectomy due to recurrent episodes of acute tonsillitis. In the control group, which also had 25 subjects, only serum samples were taken as obtaining tissue samples would not have been ethically appropriate. ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO) and malondialdehyde (MDA) were measured in the serum and tissue samples of patients and control group subjects. The serum values of both groups were compared. In addition, the tissue and serum values of patients were compared. Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group were significantly higher than those of the control group (p < 0.001), the antioxidant enzymes CA and CAT values of the patient group were significantly lower than those of the control group (p < 0.001). In addition, while CA, CAT and NO enzyme levels were found to be significantly higher in the tonsil tissue of the patient group when compared to serum levels (p < 0.05), there was no difference between tissue and serum MDA and ADA activity (p > 0.05). Elevated ADA activity may be effective in the pathogenesis of chronic tonsillitis both by impairing tissue structure and contributing to SOR formation.

[Significance of CD123 in histiocytic necrotizing lymphadenitis].

OBJECTIVE: To investigate the mode of presentation, cytologic features of the plasmacytoid dendritic cells (pDC), and the expression of CD123 and its significance in Kikuchi's disease. METHODS: CD123 expression was evaluated by EliVision immunohistochemical staining in formalin-fixed and paraffin-embedded tissues from 30 cases of Kikuchi's disease, 5 cases of T cell lymphoma, 10 cases of reactive lymphoid hyperplasia and 10 cases of chronic tonsillitis. RESULTS: Clusters of CD123 positive PDC were observed in Kikuchi's disease (28 of 30 cases, 93.3%) and the staining intensity was more prominent in the PDC at the periphery of the lesion and around the high endothelial venule-like vessels. CD123 showed three staining patterns: membranous (10 cases, 33.3%), cytoplasmic (10 cases, 33.3%), and membranous and cytoplasmic (8 cases, 26.7%). In the control group, CD123 showed cytoplasmic staining in reactive hyperplasia and chronic tonsillitis. Regarding the staining intensity, 12 of 28 cases (42.9%) were 3+ for CD123, 8 of 28 cases (28.6%) were 2+, and 8 of 28 cases (28.6%) were 1+. In contrast, PDC clusters with 1+ staining intensity were observed in 1 of 10 cases of reactive lymphoid hyperplasia; 2 of 10 chronic tonsillitis diseases; and much less in T cell lymphoma. CONCLUSIONS: Large cluster of PDC is detected in both proliferative and necrotizing types of Kikuchi's disease, making this a useful adjunctive diagnostic marker.

Possible role of nano-sized particles in chronic tonsillitis and tonsillar carcinoma: a pilot study.

This study aimed to evaluate the palatine tonsils of patients with chronic tonsillitis and spinocellular carcinoma to determine the presence of nano-sized particles. Tonsil samples from adult patients with chronic tonsillitis and spinocellular carcinoma of the palatine tonsil were dried and analyzed using a scanning electron microscope with the X-ray microprobe of an energy-dispersive spectroscope. Demographic data and smoking histories were obtained. The principal metals found in almost all tissues analyzed were iron, chromium, nickel, aluminum, zinc, and copper. No significant difference in elemental composition was found between the group of patients with chronic tonsillitis and the group with spinocellular carcinoma of the palatine tonsil. Likewise, no significant difference was found between the group of smokers and the group of nonsmokers. The presence of various micro- and nano-sized metallic particles in human tonsils was confirmed. These particles may potentially cause an inflammatory response as well as neoplastic changes in human palatine tonsils similar to those occurring in the lungs. Further and more detailed studies addressing this issue, including studies designed to determine the chemical form of the metals detected, studies devoted to quantitative analysis, biokinetics, and to the degradation and elimination of nanoparticles are needed for a more detailed prediction of the relation between the diagnosis and the presence of specific metal nanoparticles in tonsillar tissue.

[Chromogenic in situ hybridization in diagnostics of Epstein-Barr-virus infection in chronic tonsillitis].

In the issue we demonstrate results of Epstein-Barr virus (EBV) detection by chromogenic in situ hybridization (CISH) in epithelial and lymphoid cells of the palatine tonsil in patients with chronic tonsillitis. Virus genome detections were performed using RNA-probes with digoxigenin-labeled oligonucleotides which target EBV RNA, notably RNA-transcripts of virus genomic DNA. The obtained data confirm the virus lymphotropism and also tropism to epithelial cells of both surface and cryptal epithelium of the palatine tonsil. CISH method in combination with immunohistochemical identification of virus protein products opens new possibilities for clinicopathological monitoring of the different clinical forms of the chronic tonsillitis, as well as new horizon for understanding intrinsic role of EBV in tonsillar pathology.

Exhaled nitric oxide levels in children with chronic adenotonsillar disease.

Exhaled nitric oxide (eNO) is a highly reactive biological mediator that has recently been associated with chronic tonsillar disease in adults, but there are no published data concerning eNO levels in their pediatric counterparts. The aim of this study is to measure mean eNO levels in children with chronic adenotonsillitis or adenotonsillar hypertrophy, and assess the effects of potential confounding factors. Children aged 3-17 years were divided into three groups (chronic adenotonsillitis, adenotonsillar hypertrophy and controls). Their eNO levels were measured in accordance with the international guidelines, and their other clinical and anamnestic characteristics were recorded. The mean eNO level in the children with chronic adenotonsillitis was slightly higher than that in the other groups, but there was no statistically significant between-group difference. Age (p=0.009), allergy (p=0.05) and body mass index (p=0.03), but not the mean grade of adenoidal or tonsil hypertrophy, were all statistically related to mean eNO levels. These preliminary results indicate the lack of an increase in mean eNO levels in children with chronic adenotonsillar disease, with no substantial difference between children with chronic adenotonsillitis and those with adenotonsillar hypertrophy.

Spatially visualized single-cell pathology of highly multiplexed protein profiles in health and disease.

Deep molecular profiling of biological tissues is an indicator of health and disease. We used imaging mass cytometry (IMC) to acquire spatially resolved 20-plex protein data in tissue sections from normal and chronic tonsillitis cases. We present SpatialViz, a suite of algorithms to explore spatial relationships in multiplexed tissue images by visualizing and quantifying single-cell granularity and anatomical complexity in diverse multiplexed tissue imaging data. Single-cell and spatial maps confirmed that CD68+ cells were correlated with the enhanced Granzyme B expression and CD3+ cells exhibited enrichment of CD4+ phenotype in chronic tonsillitis. SpatialViz revealed morphological distributions of cellular organizations in distinct anatomical areas, spatially resolved single-cell associations across anatomical categories, and distance maps between the markers. Spatial topographic maps showed the unique organization of different tissue layers. The spatial reference framework generated network-based comparisons of multiplex data from healthy and diseased tonsils. SpatialViz is broadly applicable to multiplexed tissue biology.

Cytokine production in patients with recurrent acute tonsillitis: analysis of tonsil samples and blood.

The aim of this study was to examine T cell function in tonsils of patients with recurrent acute tonsillitis (RAT) or peritonsillar abscess (PTA) by analyzing the cytokine production following T cell receptor (TCR) and co-receptor stimulation with a combination of anti-CD3 and anti-CD28 antibodies. The release of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A from isolated, stimulated T cells of 27 palatine tonsils (10 RAT, 7 PTA, 10 tonsils without inflammation) was measured via a bead-based flow cytometric analysis. The results were compared with the cytokine release of isolated peripheral T cells in a subset of the same patients (6 PTA, 4 patients without signs of inflammation in the blood). TCR stimulation increased the concentration of released cytokines in tonsil and blood as well as in different forms of inflammation and tissue with no inflammation. Stimulation increased the pro-inflammatory cytokines TNF-α, IFN-γ, and IL-2 more than the anti-inflammatory cytokines IL-4 and IL-10 in tonsil and blood samples in RAT, PTA, and samples without inflammation. Blood of patients with PTA showed a higher pro-inflammatory cytokine level compared to the samples of patients without inflammation. T cells in tonsils are fully responsive and competent for antigen-induced cytokine production in RAT and PTA. One should be aware that tonsillectomy, if indicated, might remove a functioning immune organ. Tonsillotomy might be an alternative even in adults to maintain immunological function.

miRNA profiling of B-cell subsets: specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes.

MicroRNAs (miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to establish miRNA profiles of naïve, germinal center (GC) and memory B cells, and validate their expression patterns in normal lymphoid tissues. Quantitative (q) RT-PCR profiling revealed that several miRNAs were elevated in GC B cells, including miR-17-5p, miR-106a and miR-181b. One of the most abundant miRNAs in all three B-cell subsets analyzed was miR-150, with a more than 10-fold lower level in GC B cell as compared with the other two subsets. miRNA in situ hybridization (ISH) in tonsil tissue sections confirmed the findings from the profiling work. Interestingly, gradual decrease of miR-17-5p, miR-106a and miR-181b staining intensity from the dark to the light zone was observed in GC. A strong cytoplasmic staining of miR-150 was observed in a minority of the centroblasts in the dark zone of the GC. Inverse staining pattern of miR-150 against c-Myb and Survivin was observed in tonsil tissue sections, suggesting possible targeting of these genes by miR-150. In line with this, the experimental induction of miR-150 lead to reduced c-Myb, Survivin and Foxp1 expression levels in the Burkitt's lymphoma cell line, DG75. In conclusion, miRNA profiles of naïve, GC and memory B cells were established and validated by miRNA ISH. Within the GC cells, a marked difference was observed between the light and the dark zone.

Acute myopericarditis complicating acute tonsillitis: a prospective study.

OBJECTIVES: We describe a prospective study of 100 consecutive cases of acute tonsillitis tested for cardiac involvement. There was 1 clear-cut case of acute myopericarditis and 5 more patients with pathological findings suggesting cardiac complication. METHODS: During a 6-month period (November 2006 to April 2007), we prospectively studied 100 consecutive patients admitted to our department with acute tonsillitis for the purpose of detecting acute myopericarditis. We obtained for each patient a serial electrocardiogram and echocardiogram, and took blood samples. All blood samples were analyzed for the presence of the marker troponin 1 and for cardiac enzymes. RESULTS: One patient (male) had a definitive diagnosis of myopericarditis, and another 5 patients (3 of whom were female) had abnormal cardiac findings suggestive of myopericarditis. CONCLUSIONS: Otolaryngologists should be aware of the possibility of cardiac involvement in acute tonsillitis and perform an adequate workup whenever such a possibility is suspected.

The differences in the expression of fractalkine and its receptor in conditions of tonsillar hypertrophy and chronic tonsillitis.

OBJECTIVE: Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples. METHODS: The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C>T (T280M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated. RESULTS: Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p<0.05). CONCLUSION: Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis.

Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children.

An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to -0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC(90) more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total T >MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.