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PubMed1988

Pharmacokinetic evaluation of ofloxacin in serum and tonsils.

The bioavailability of ofloxacin in tonsil tissue, after a single oral dose of 200 mg 2 h before surgery, was evaluated in 14 patients undergoing tonsillectomy for recurrent or chronic infection. A blood specimen was obtained just before drug administration and at the time of tonsillectomy, together with a specimen of tonsil tissue. The mean values of the serum and tonsil concentrations 2 h after a single dose of 200 mg were 1.17 mg/l +/- 0.47 and 1.61 mg/l +/- 0.62 respectively with a mean tonsil/serum ratio of 1.40 +/- 0.19. These values indicate good penetration of ofloxacin into tonsil tissue. No clinical or biological side-effects were observed.

Administration, Oral↗
PubMed1989

Treatment of patients with acute recurrent tonsillitis due to group A beta-haemolytic streptococci: a prospective randomized study comparing penicillin and amoxycillin/clavulanate potassium.

The failure of penicillin to eradicate Group A beta-haemolytic streptococcal tonsillitis may be caused by beta-lactamase producing bacteria in the tonsillar tissue. A prospective randomized clinical study comparing the efficacy of penicillin-V potassium with amoxycillin plus clavulanate potassium (Augmentin) in the treatment of acute episodes of recurrent streptococcal tonsillitis was conducted. Twenty children were included in each group. Surface tonsillar cultures were obtained before therapy, ten days after termination of therapy, and then once every two months for up to one year. beta-Lactamase producing aerobic and anaerobic bacteria were present in 34 of the 40 (85%) tonsillar cultures prior to treatment. Group A beta-haemolytic streptococci were eradicated in 14 of 20 (70%) patients treated with penicillin and in all those treated with amoxycillin/clavulanate potassium (P less than 0.001). In a one-year follow-up, 11 of the 19 patients treated with penicillin and two of the 18 treated with amoxycillin/clavulanate potassium had recurrent streptococcal tonsillitis (P less than 0.005). This study demonstrates the efficacy of amoxycillin/clavulanate potassium in the therapy of acute episodes of recurrent tonsillitis and prevention of recurrent infection.

Adolescent↗
PubMed2001

Acute necrotizing bacterial tonsillitis with Clostridium perfringens.

Bacterial infection with Clostridium perfringens in children less than 2 years of age is frequently associated with meningitis, necrotizing gastrointestinal infection, and postoperative infections. However, a review of the literature reveals no reports of these bacteria infecting the tonsils. A 9-month old black female was found unresponsive at the baby-sitter's and was rushed to the hospital. Shortly after admission to the emergency department death was pronounced. An autopsy performed on this otherwise healthy infant revealed shock and acute necrotizing bacterial tonsillitis. The initial report of this infant's death was questionable sudden infant death syndrome and questionable smothering. Postmortem cerebrospinal fluid, blood, and lung cultures grew pure colonies of C. perfringens. The necrotizing tonsil revealed no significant gross lesions. Microscopically, large numbers of gram-positive rods were easily recognized and were compatible with C. perfringens. Because the oropharynx is a common portal of entry for infectious agents, it is essential to sample tissues of Waldeyer's ring and especially the tonsils to find infectious diseases that may become systemic.

Acute Disease↗
PubMed1999

Activation of CD8 T cells normalizes and correlates with the level of infectious provirus in tonsils during highly active antiretroviral therapy in early HIV-1 infection.

OBJECTIVES: To study the effects of antiretroviral therapy on T cell activation in blood and tonsils from HIV-1 infected individuals in relation to CD4 cell count, plasma viremia, and infectious HIV-1 provirus. DESIGN: A 48-week study of viral load and T cell subsets in blood and tonsils from 12 HIV-1-positive individuals with a mean CD4 cell number of 400 x 10(6) cells/l treated with a combination of zidovudine, lamivudine, and indinavir. METHODS: Tonsil biopsies and blood samples were collected at regular intervals. Lymphocytes were phenotyped and quantified by three-color flow cytometry; infectious provirus was quantified by a limiting dilution assay. HIV-1-negative individuals were included as controls. RESULTS: The fraction of tonsillar CD8 T cells expressing CD69, CD38, or HLA-DR in the patients with suppressed virus replication declined to levels comparable with that in controls by 48 weeks and showed a strong positive correlation with tonsillar infectious provirus and plasma viremia. The level of CD4 T cell activation was within normal range in tonsils throughout the study. The fraction of HLA-DR+ cells within CD4 and CD8 T cells in blood declined rapidly in parallel with plasma viremia but remained slightly higher compared with that in uninfected individuals. CONCLUSION: Antiretroviral therapy normalizes tonsillar CD8 T cell activation in HIV-1-positive individuals in parallel with suppression of viral replication, indicating reduced CD8 cell turnover. Normal tonsillar CD4 T cell activation suggests limited CD4 cell turnover in early HIV infection. Activated CD8 T cells in lymphoid tissue is superior to that in blood as an immunological marker for the virological response to antiretroviral therapy.

ADP-ribosyl Cyclase↗
PubMed2005

Rapid PrP(Sc) detection in lymphoid tissue and application to scrapie surveillance of fallen stock in Japan: variable PrP(Sc) accumulation in palatal tonsil in natural scrapie.

Rapid western blot (WB) procedure for an abnormal isoform of prion protein (PrP(Sc) ) detection in lymphoid tissues was established and has been applied to the surveillance of fallen stock. In this program, brain and palatal tonsil were examined by WB and three cases of sheep scrapie were detected. While one clinically scrapie-infected sheep harbored PrP(Sc) in the brain and palatal tonsil, the two sheep in the pre-clinical stage harbored PrP(Sc) in the brain, but not in the palatal tonsil. This study shows that PrP(Sc) accumulation in palatal tonsil is variable in natural scrapie, even among genetically susceptible sheep.

Animals↗
PubMed1993

High frequency of spontaneous interferon-gamma-producing cells in human tonsils: role of local accessory cells and soluble factors.

The frequency of mononuclear cells (MNC) spontaneously secreting interferon-gamma (IFN-gamma) has been examined in freshly isolated cell suspensions from human palatine tonsils. Two-site reverse enzyme-linked immunospot (ELISPOT) analyses, involving short term (20 h) incubation of MNC in the absence of any added exogenous stimulus, revealed that tonsillar MNC suspensions contain exceptionally large numbers of cells secreting IFN-gamma. No significant differences were observed when comparing the frequency of IFN-gamma-producing cells between cell suspensions obtained from hyperplastic and tonsillitis specimens. Cell-sorting experiments disclosed that spontaneous tonsillar IFN-gamma production was essentially contributed by CD4+ T cells, and required the presence of accessory cells and/or soluble factors to be detected. Thus, depletion of plastic adherent cells or monocytes from the tonsillar MNC suspensions resulted in reduced numbers of detectable IFN-gamma-secreting cells. Addition of very small numbers of autologous monocytes restored spontaneous IFN-gamma production in tonsillar MNC cultures depleted of monocytes. Neutralization of endogenous IL-1 beta and IL-2, as well as blocking of the IL-2 receptor, also decreased IFN-gamma production from unfractionated tonsillar cells. Addition of exogenous IL-1 beta restored IFN-gamma production in cultures of tonsillar MNC depleted of plastic adherent cells. Furthermore, IL-1 beta synergized with IL-2 by tonsillar MNC depleted of plastic adherent cells. Furthermore, IL-1 beta synergized with IL-2 by increasing intracellular as well as cell-free levels of IFN-gamma in cultures of unfractionated tonsillar MNC. This study further establishes that the tonsils are highly active immunological organs containing large numbers of T cells spontaneously producing IFN-gamma whose detection is contingent upon the presence of functional accessory cells. It also demonstrates that concomitant production of IL-1 beta and IL-2 occurs in tonsils and is necessary to maintain ongoing synthesis and extracellular accumulation of IFN-gamma in these organs.

Adolescent↗
PubMed1995

Increased dimeric IgA-producing B cells in tonsils in IgA nephropathy determined by in situ hybridization for J chain mRNA.

The origin of mesangial IgA deposits in IgA nephropathy (IgAN) remains obscure. A significant proportion of deposited immunoglobulin is dimeric (J chain-positive). Previous studies of J chain expression within lymphoid tissue in IgAN have utilized antibodies which other investigators have found to be non-specific. To address this problem, we have developed and in situ hybridization (ISH) method for the detection of J chain mRNA within IgA plasma cells. Tonsils from 12 patients with IgAN and 12 controls were studied using (i) non-isotopic ISH for J chain mRNA, and (ii) combined immunofluorescence (IF) and fluorescent ISH. J chain mRNA-positive cells were identified in germinal centres, and within the subepithelial and interfollicular zones. A greater number of J chain mRNA-positive cells were found in the germinal centres of patients (mean 57.7 +/- 4.6 cells/10(5) micron2) compared with controls (mean 36.9 +/- 3.5 cells/10(5) micron2) (P < 0.001). Combined IF and fluorescent ISH showed a greater proportion of J chain mRNA-positive interfollicular IgA cells in patient tonsils (32 +/- 3.4%) compared with controls (21 +/- 2.3%; P < 0.02). These results indicate a shift towards dimeric IgA production in the tonsils in IgAN. In addition, the finding of excess numbers of J chain-positive Iga-negative cells within germinal centres suggests that an abnormality may be present at the B cell differentiation stage before IgA switching. These results further highlight immune abnormalities within the tonsil as a central feature of abnormal polymeric IgA biology in this common form of glomerulonephritis.

Adolescent↗
PubMed1979

Particularity of local immunity in the nasopharynx. Parallel study of surface receptors and cell-mediated immune responses in cells derived from palatine or pharyngeal tonsils and blood.

Immunological functions of the pharyngeal tonsil, palatine tonsils and blood leucocytes of children undergoing tonsillectomy were evaluated by determining T or B lymphocytes, the response to mitogens, and the cell-mediated immunological responses to tuberculin. In all the test systems used similar results were obtained with cells derived from either the palatine or pharyngeal tonsils. The mean percentage of T lymphocytes was significantly higher in the peripheral blood than in tonsils, but the reverse was true of B lymphocytes. The reaction to PHA was lower in tonsillar cell culture than in blood cell culture, but tonsillar cells reacted better to Con A than blood cells. In lymphocyte transformation tests tonsillar cells reacted to specific antigen (tuberculin) and this reaction was significantly higher than that of the parallelly tested blood lymphocytes. Further, in about 50% of the children tested, tuberculin caused migration inhibition of the mixture containing tonsillar cells and guinea pig peritoneal cells. Surprisingly, nearly identical results were obtained if migration inhibition test was performed with tonsillar cells alone. Consequently, poorly migrating tonsillar cells are nevertheless usable for direct migration inhibition testing.

Antigens, Surface↗
PubMed1998

An immunohistochemical study of bovine palatine and pharyngeal tonsils at 21, 60 and 300 days of age.

An immunohistochemical study was performed on three groups of young cattle (21, 60 and 300 days of age). Tonsils (palatine and pharyngeal) and mucosae (nasal and oral) were removed. Eight monoclonal antibodies (specific for CD3, CD2, CD4, CD8, WC1, cell-surface IgM, cell-surface IgG and MHC class II molecules) and an avidin/biotin complex method on frozen sections were used. The immunological cytoarchitecture of bovine tonsils is similar to that of human tonsils. Nevertheless, these lymphoid tissues are not fully developed during the first weeks of life: T and B dependent areas not well-differentiated, few germinal centres, few intra-epithelial WC1+ T lymphocytes. In contrast, at 2 months, tonsils possess all the elements of a mucosa-associated lymphoid tissue (MALT). Tonsillar or mucosal epithelium is infiltrated by a large number of CD8+, WC1+ T lymphocytes and cells which express MHC class II molecules. Between 21 and 60 days, the number of WC1+ T lymphocytes increase markedly in the tonsillar epithelium. These results accredit the hypothesis that the presence of antigens has an effect on the localization of these lymphocytes at these sites.

Aging↗
PubMed2006

Histology, immunohistochemistry and ultrastructure of the tonsil of the soft palate of the horse.

The tonsil of the soft palate was an oval, flat structure located centro-rostrally on the oral surface of the soft palate. Its stratified squamous non-keratinized epithelium was perforated by holes or small crypts the deeper parts of which were loosely spongiform inter-digitated with lymphoid tissue. These unusual features have not previously been reported in tonsils of any species. Crypts and reticulated epithelium as found in the lingual and palatine tonsils were not observed. Lectins showed varying affinities for specific layers of the epithelium. M cells were not observed. A few Langerhans cells were distributed among surface epithelial cells. Lymphoid tissue was arranged loosely and in isolated lymphoid follicles in the subepithelial lamina propria mucosae. Although IgA+ cells and macrophages were proportionately more numerous the amount of lymphoid tissue was much less than in the lingual and palatine tonsils. Most of the follicular germinal centres lacked a darkly stained corona. CD4 positive were more numerous than CD8+ lymphocytes and were distributed in the parafollicular and inter-follicular areas. Large clusters of mucus acini positive for glycogen, acidic and neutral mucopolysaccharides separated lymphoid tissue from deeply placed striated muscle. Only a few high endothelial venules were observed in the parafollicular and inter-follicular areas. These had relatively few vesiculo vacuolar or other organelles in their high endothelial cells and few lymphocytes attaching to their walls.

Animals↗
PubMed1973

Relationship of adenovirus to lymphocytes in naturally infected human tonsils and adenoids.

Purified lymphocytes from human tonsil and adenoid specimens were cultured with and without phytohemagglutinin. Adenovirus was isolated from lymphocytes of 8 of 90 specimens tested. With one exception, it was necessary to culture the lymphocytes before infectious virus could be detected. Phytohemagglutinin stimulation enhanced the recovery of virus. The results suggest that lymphocytes in tonsils and adenoids may be naturally infected with adenovirus and that, in positive cultures, at least 1 of every 10(7) cells harbors virus or viral precursor at initiation of the cultures. Adenovirus was demonstrated directly in fresh suspensions of unpurified cells from tonsils and adenoids in seven cases. In five of these cases, at least 1 of every 10(6) cells contained infectious virus. Adenovirus was isolated from 61 (62%) of 98 tonsil and adenoid specimens by the conventional method of tissue fragment culture after various periods of cultivation. The viruses isolated were of serotypes 1, 2, 5, and 6.

Adenoids↗
PubMed1999

Immunomagnetic isolation of Streptococcus suis serotypes 2 and 1/2 from swine tonsils.

Isolation of specific serotypes of Streptococcus suis from the tonsils, nasal cavities, and genital tract is difficult, since low-pathogenic serotypes and untypeable strains also inhabit these sites. An immunomagnetic separation (IMS) technique for the selective isolation of S. suis serotypes 2 and 1/2 was standardized. Superparamagnetic polystyrene beads (immunomagnetic beads or IMB) were coated with either a purified monoclonal antibody (MAb) directed to a capsular sialic acid-containing epitope or purified rabbit immunoglobulin G (polyclonal antibody [PAb]), both specific for S. suis serotypes 2 and 1/2. The amount of antibodies required for optimum coating of the beads, the number of IMB required for optimum bacterial recovery, and the nonspecific carryover were considerably higher with the MAb-IMS technique than with the PAb-IMS technique. The sensitivity of the IMS technique was 10(1) CFU/0.1 g of tonsil. The presence of serotype 1/2 bacteria did not considerably affect the recovery rate of a serotype 2 strain and vice versa. To validate the technique, PAb-coated beads were used to study 192 tonsils from animals from S. suis serotype 2- or 1/2-infected herds. Results showed that significantly more positive tonsils were detected by the IMS technique than by the standard procedure. This method represents an innovative and highly sensitive approach for the isolation of S. suis serotypes 2 and 1/2 from carrier animals.

Animals↗
PubMed2000

Cells expressing the Epstein-Barr virus growth program are present in and restricted to the naive B-cell subset of healthy tonsils.

In this paper we demonstrate, for the first time, that Epstein-Barr virus (EBV)-infected cells expressing the lymphoblastoid growth program are present in healthy carriers of the virus. Previously we observed that latently infected naive B cells are present in tonsils only when viral replication is detected, suggesting that these may represent newly infected B cells. We have tested this idea by performing a reverse transcription-PCR analysis for the expression of latent genes (EBNA2 and the EBNA3s) that are characteristically expressed only by newly infected cells expressing the growth latency program. EBNA2 expression is regularly detected in purified naive (IgD(+)) tonsillar B cells (13 of 16 tonsils tested) but was never found in the IgD(-) population (0 of 16). More detailed analysis revealed that the mRNAs for the latent genes EBNA1 (3 of 3 tonsils tested), EBNA3a (3 of 5), EBNA3b (3 of 5), EBNA3c (3 of 5), LMP1 (6 of 6), and LMP2 (5 of 6) were also present in the IgD(+) population, but the EBNA1Q-K transcript, characteristic of nonlymphoblastoid forms of latency, was never detected (0 of 6). Finally, we demonstrate that the latently infected naive (IgD(+)) cells express CD80 (B7.1), a marker characteristically expressed on activated naive lymphoblasts but absent from resting naive B cells. The infected naive (IgD(+)) population in the tonsil therefore has the viral and cellular phenotype of a B-cell directly infected with EBV-an activated lymphoblast expressing the growth program.

B-Lymphocytes↗
PubMed2004

Epstein-Barr virus infection in ex vivo tonsil epithelial cell cultures of asymptomatic carriers.

Epstein-Barr virus (EBV) is found frequently in certain epithelial pathologies, such as nasopharyngeal carcinoma and oral hairy leukoplakia, indicating that the virus can infect epithelial cells in vivo. Recent studies of cell lines imply that epithelial cells may also play a role in persistent EBV infection in vivo. In this report, we show the establishment and characterization of an ex vivo culture model of tonsil epithelial cells, a likely site for EBV infection in vivo. Primary epithelial-cell cultures, generated from tonsil explants, contained a heterogeneous mixture of cells with an ongoing process of differentiation. Keratin expression profiles were consistent with the presence of cells from both surface and crypt epithelia. A small subset of cells could be latently infected by coculture with EBV-releasing cell lines, but not with cell-free virus. We also detected viral-DNA, -mRNA, and -protein expression in cultures from EBV-positive tonsil donors prior to in vitro infection. We conclude that these cells were either already infected at the time of explantation or soon after through cell-to-cell contact with B cells replicating EBV in the explant. Taken together, these findings suggest that the tonsil epithelium of asymptomatic virus carriers is able to sustain EBV infection in vivo. This provides an explanation for the presence of EBV in naso- and oropharyngeal pathologies and is consistent with epithelial cells playing a role in the egress of EBV during persistent infection.

Adolescent↗
PubMed1992

Human tonsil intraepithelial B cells: a marginal zone-related subpopulation.

AIMS: To determine if intraepithelial B cells in reactive human palatine tonsils were similar to the marginal zone cells of the spleen and Peyer's patches. METHODS: Reactive human palatine tonsils were studied using conventional methods of light microscopy, electron microscopy, and a panel of monoclonal antibodies for leucocyte common antigens. RESULTS: Clinically important numbers of marginal zone-related B cells around the mantle zone were absent in lymphoid follicles, but in the cryptal epithelium there were abundant lymphoid cells with centrocyte-like nuclei and clear cytoplasm, intermingled with macrophages and plasma cells. The immunophenotype of these intraepithelial B cells was distinctive and similar to that found in the splenic marginal zone cells (IgM+, IgD-, CD23-, CD10-, CD35+, CD21+, bc12+, KB61+). CONCLUSIONS: Intraepithelial B cells in human tonsil could represent the counterpart of the marginal zone described in Peyer's patches. Their presence within the epithelium could reflect the destination for the malignant B cells in the lymphoepithelial lesion of mucosa associated lymphoid tissue (MALT) lymphomas. Human palatine tonsil lymphoid tissue has morphological, immunophenotypic, and pathological features similar to those of MALT.

B-Lymphocytes↗
PubMed1993

CD23/Fc epsilon RII expression on phytohemagglutinin-A- or phorbol-12myristate-13acetate-Ca(2+)-activated human tonsil T cells.

The low-affinity Fc receptor for IgE, CD23/Fc epsilon RII, has been expressed in T cell lines and pathologic T cells, but its presence on normal human T cells is still debated. We studied the expression of CD23/Fc epsilon RII on purified T cells from normal peripheral blood mononuclear cells (PBMC) or tonsil T cells stimulated with 10 micrograms/ml phytohemagglutinin A (PHA) or phorbol-12myristate- 13acetate (PMA) Ca2+. Using two-dimensional flow cytometry, the tonsil T-cell-enriched population showed > 10% of CD23/Fc epsilon RII expression when coexpressed with the CD3 antigen. CD4+ T cells appear to be principally involved in the expression of CD23/Fc epsilon RII, although we were unable to detect a clear expression of CD23/Fc epsilon RII in PBMC that were activated with either PHA or PMA Ca2+. PHA stimulation resulted in the release of IgE binding factor (IgEBF). The induction of CD23/Fc epsilon RII expression in PHA- and PMA-Ca(2+)-activated T cells was enhanced by IL-4, but not by IgE or IL-6. IL-4 also augmented the PHA- and PMA-Ca(2+)-induced release of IgEBF. The addition of supernatant from the Epstein-Barr virus (EBV)-infected cell line to PHA- or PMA-Ca(2+)-stimulated tonsil T cells did not increase CD23/Fc epsilon RII expression. The expression of CD23/Fc epsilon RII mRNA was detected in RNA prepared from a tonsil T-cell-enriched population by Northern blot analysis.

Blotting, Northern↗
PubMed2006

One-off streptococcal serologic testing in young children with recurrent tonsillitis.

OBJECTIVES: Recurrent acute tonsillitis in children under 4 years of age is usually viral, making antibiotic therapy inappropriate and the indication for tonsillectomy uncertain. Identifying those young children with bacterial infections is therefore important. The purpose of this study was to determine whether one-off streptococcal serologic testing is a useful tool in assessing recurrent acute tonsillitis in young children. METHODS: We performed a retrospective study of 45 children (35 male and 10 female) under the age of 4 years who were found by a staff otolaryngologist to have recurrent acute tonsillitis over a 5-year period and had one-off serologic testing for anti-streptolysin O titers and anti-deoxyribonuclease B levels. Data were collected by chart review. RESULTS: Three children (6.7%) had clearly positive titers for either one or both streptococcal antibodies. Children with negative serologic results were significantly less likely to have shown a significant response to antibiotic therapy for their acute episodes (26% versus 100%; p = .026). Nine children (20%) eventually underwent tonsillectomy, all of whom had negative serologic results. CONCLUSIONS: Anti-streptolysin O and anti-deoxyribonuclease B levels may aid clinical evaluation of recurrent acute tonsillitis in young children in differentiating between those cases due to group A beta-hemolytic Streptococcus and those that are viral in origin.

Acute Disease↗
PubMed2006

Cost-effectiveness of tonsillectomy for recurrent acute tonsillitis.

OBJECTIVES: We used a retrospective case series to perform a preliminary study to determine the clinical effectiveness and cost-effectiveness of tonsillectomy for recurrent acute tonsillitis. METHODS: We studied 25 children and 16 adults who had tonsillectomy for recurrent acute tonsillitis. The adult patients and the children's caregivers were asked to respond to a questionnaire regarding the efficacy of their tonsillectomy. The cost of medical care and the work disability cost for tonsillitis and for tonsillectomy were calculated. We then applied the technique of break-even time analysis to assess when the total health care cost savings from surgery overtook the total cost of tonsillectomy. RESULTS: In children, the overall economic costs (medical costs and work-related costs) were recovered at 1.6 years after tonsillectomy (break-even point). In adults, the overall economic costs (medical costs and work-related costs) were recovered at 2.5 years after tonsillectomy (break-even point). CONCLUSIONS: Tonsillectomy for recurrent acute tonsillitis is both clinically effective and cost-effective for children and adults in Japan.

Acute Disease↗