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Persistence and reactivation of bovine herpesvirus 1 in the tonsils of latently infected calves.

Bovine herpesvirus 1 (BHV-1), like other members of the Alphaherpesvirinae subfamily, establishes latent infection in sensory neurons. Reactivation from latency can occur after natural or corticosteroid-induced stress culminating in recurrent disease and/or virus transmission to uninfected animals. Our previous results concluded that CD4(+) T cells in the tonsil and other adjacent lymph nodes are infected and undergo apoptosis during acute infection (M. T. Winkler, A. Doster, and C. Jones, J. Virol. 73:8657-8668, 1999). To test whether BHV-1 persisted in lymphoreticular tissue, we analyzed tonsils of latently infected calves for the presence of viral DNA and gene expression. BHV-1 DNA was consistently detected in the tonsils of latently infected calves. Detection of the latency-related transcript (LRT) in tonsils of latently infected calves required nested reverse transcription-PCR (RT-PCR) suggesting that only a few cells contained viral DNA or that LRT is not an abundant transcript. bICP0 (immediate-early and early transcripts), ribonucleotide reductase (early transcript), and glycoprotein C (late transcript) were not detected by RT-PCR in latently infected calves. When reactivation was initiated by dexamethasone, bICP0 and ribonucleotide reductase transcripts were detected. Following dexamethasone treatment, viral nucleic acid was detected simultaneously in trigeminal ganglionic neurons and lymphoid follicles of tonsil. LRT was detected at 6 and 24 h after dexamethasone treatment but not at 48 h. Dexamethasone-induced reactivation led to apoptosis that was localized to tonsillar lymphoid follicles. Taken together, these findings suggest that the tonsil is a site for persistence or latency from which virus can be reactivated by dexamethasone. We further hypothesize that the shedding of virus from the tonsil during reactivation plays a role in virus transmission.

Animals↗

Lymphoid progenitor cells in human tonsils.

To investigate the occurrence of lymphoid progenitor cells in human tonsils, we studied tonsils from children and adults by immunohistochemistry by using a panel of antibodies to antigens associated with lymphoid progenitor cells, including terminal deoxynucleotidyl transferase (TdT), CD10 (CALLA), CD34, CD99 (p30/32mic2), and CD117 (c-kit), and compared them to reactive lymph nodes. Lymphoid progenitor cells, positive for TdT, CD10, and CD99, but not CD34 or CD117, were readily identified in tonsils from children and adults (TdT, 14 of 15; CD10, 15 of 15; CD99, 11 of 15), but were rarely present in lymph nodes (TdT, 1 of 8; CD10, 1 of 8; CD99, 0 of 8). Lymphoid progenitor cells in tonsils were localized to discrete foci at the periphery of lymphoid lobules adjacent to fibrous septae. Lymphoid progenitor cells are present in human tonsils, and the tonsils are a potential site of postnatal lymphopoiesis. The presence of lymphoid progenitor cells in human tonsils should not be confused with lymphoblastic lymphoma or leukemia.

Adolescent↗

The cellular differentiation of M cells from crypt undifferentiated epithelial cells into microvillous epithelial cells in follicle-associated epithelia of chicken cecal tonsils.

To clarify the cellular origin and the fate of M cells, detailed distributions of the epithelial cells were investigated scanning electron microscopically on the follicle-associated epithelia (FAE) of chicken cecal tonsils. The distribution of M cells was closely related with the situation of the crypt orifices in chicken cecal tonsils. In undeveloped cecal tonsils, the intestinal crypts were localized at the periphery of the FAE. In these tonsils, M cells without microvilli (M(0)) were predominantly populated in the basal region of the FAE, whereas goblet cells and microvillous epithelial cells (MV) were more distributed in the middle to the apical region of the FAE. A few M cells with short microvilli were dispersed throughout the FAE. Significantly shrunk MV (MVs) clustered together in transitional portions from the lateral face to the roof of the FAE. In well-developed cecal tonsils, the crypts also opened at the lateral surface in addition to the periphery of the FAE. In these tonsils, the M(0) accumulated densely in the small areas around the crypt orifices exclusively. No sign of exfoliation of apoptotic epithelial cells was found in the M(0)-accumulated areas and at their peripheral boundaries. The MVs were often clustered in the central regions among the crypt orifices in addition to the roof of the FAE. These findings suggest that M cells are directly derived from the undifferentiated crypt epithelial cells, not fall into apoptotic cell death and further differentiate into MV in the FAE of chicken cecal tonsils.

Animals↗

Terminal deoxynucleotidyl transferase-positive cells in human tonsils.

To study the possible cellular origin of recently recognized indolent terminal deoxynucleotidyl transferase (TdT)-positive T-lymphoblastic proliferations of the tonsils and oropharynx, we studied normal human tonsils for the presence of TdT-positive cells. TdT-positive cells were readily demonstrated in the tonsils from 15 children and adults by immunohistochemical staining. TdT-positive cells were distributed in discrete foci at the periphery of lobules of lymphoid tissue and adjacent to fibrous septa and had the morphologic features of small to medium-sized lymphocytes. Double-antibody staining indicated the TdT-positive cells had the phenotype of uncommitted early lymphoid precursors (CD3-, CD79a-, CD10-). Foci of TdT-positive cells were not identified in 6 reactive lymph nodes studied as controls. These studies indicate that tonsils, like bone marrow and thymus, are sites of lymphopoiesis. The presence of TdT-positive precursor cells in human tonsils may be a factor in the pathogenesis of recently described indolent T-lymphoblastic proliferations involving the tonsils and oropharynx. The presence of TdT-positive cells in human tonsils should not be misinterpreted as evidence of lymphoblastic lymphoma or leukemia.

Adolescent↗

Immunohistochemical analysis of CD71, CD98 and CD99 activation antigens in human palatine and nasopharyngeal tonsils.

OBJECTIVE: Tonsils (palatine and nasopharyngeal) are immunologically active tissues. Due to their anatomical location, they are considered to be the initial defense barrier against the antigens entering into the respiratory and gastrointestinal tract. Tonsils act against these antigens by producing and activating the lymphocytes, which are responsible for the immune response. In order to get information regarding the distribution of cell surface antigens on the epithelial, stromal and lymphoid cells of these organs, we performed immunohistochemical staining by using antibodies against CD99, CD71 and CD98 activation antigens. METHODS: Tissue samples of 20 patients undergoing tonsillectomy and adenoidectomy who presented with recurrent tonsillitis and adenoid hypertrophy in the Otorhinolaryngology Department, Hacettepe University Medical Faculty Hospital, Ankara, Turkey in 2001, were obtained as partial tissue samples apart from pathological examination. Tissues were immunostained by the indirect immunoperoxidase method. RESULTS: Strong CD71 reactivity in macrophages was observed as an indicator of the active role of the macrophages in immunoresponse in the chronic inflammation reaction. The CD98 reactivity on the proliferative basal layer of epithelium was a usual finding, as its detection in epithelial neoplasms and proliferative states is well known. We did not observe any reactivity of CD98 in nasopharyngeal tonsil epithelium and lymphoid cells of either nasopharyngeal or palatine tonsils. The CD99 reactivity was observed in the T-cell dependent area. CONCLUSION: We determined some topographic difference in the expression of some activation antigens in the epithelial, stromal and lymphoid components of the palatine and nasopharyngeal tonsils. Further detailed studies directed to determine the role of these antigens in tonsils would help to understand the role of these molecules in inflammatory events.

Adolescent↗

[Tracheal intubation for two patients with lingual tonsil hyperplasia and prospect of difficult airway management].

Lingual tonsil hyperplasia is rare, but may cause difficult or inpossible tracheal intubation. We experienced two cases of tracheal intubation for lingual tonsil hyperplasia. A 71-yr-old man was scheduled for resection and biopsy of symptomatic hypertrophied lingual tonsils. In this patient, we performed oro-tracheal intubation by rigid laryngoscopy from left oral angle, because left hypertrophied lingual tonsils are smaller than those on the right side. A 44-yr-old man was scheduled for resection of symptomatic hypertrophied lingual tonsils after lingual tonsillitis. In this patient, we performed nasotracheal intubation using fiberoptic bronchoscopy with assist of jaw-lift and tongue-extension. When an anesthesiologist can predict the abnormality of lingual tonsils, these methods might be recommended for difficult airway and intubation. However, it is necessary to prepare a difficult airway management set including laryngeal mask airway, intubating laryngeal mask airway, fiberoptic bronchos-copy and transcutaneous tracheotomy set. And most important is preliminary evaluation of airway and cautious planning of tracheal intubation.

Adult↗

Comparative study of bacteriology in recurrent tonsillitis among children and adults.

INTRODUCTION: Diagnosis and treatment of acute tonsillitis are one of the most common problems seen at an otorhinolaryngology clinic in both adult and paediatric populations. Much has been written about bacteriology of recurrent tonsillitis but it remains a controversial topic. Despite the fact that tonsillitis is so common, consensus seems to be lacking as to the main causative organism and the differences between children and adults. The tonsillar core bacteriology of 233 patients with recurrent tonsillitis who underwent tonsillectomy from January 2000 to June 2003 is presented. METHODS: The patient population was divided into two groups, namely: the paediatric group and the adult group. 132 patients, whose age was more than 12 years, were in the adult group. 101 patients aged between two and 12 years, were in the paediatric group. The bacteriology of the children and adults were tabulated according to their species, and were compared. RESULTS: 138 patients grew single pathogenic bacteria in their tonsillar core culture, 52 grew two different pathogenic bacteria, and the rest (43) grew normal bacterial flora. Staphylococcus aureus was the most commonly-isolated bacterium and accounted for 40.9 percent of the total cultures isolated; its prevalence was the same in the adults and children. Beta-haemolytic Streptococcus was isolated in 23 percent of subjects, and was predominantly from group A (Streptococcus pyogens). Group A beta-haemolytic Streptococci was more prevalent in children. Pseudomonas aeruginosa, which rarely cause pathogenicity in tonsils, was cultured from nine (3.8 percent) of our study subjects. CONCLUSION: This study showed that Staphylococcus aureus is the most common pathogenic bacteria cultured both in adults and children. Klebsiella pneumonia, Streptococcus pneumonia, Escherichia coli and Enterobacter are more prevalent in adults. Haemophilus influenza and Streptococcus pyogens are more prevalent in children. Pseudomonas aeruginosa is not a rare causative organism in recurrent tonsillitis. Since the mechanism of activation of infection in recurrent tonsillitis is unknown, knowing the bacteriology does not help us to treat the disease. However, it may be a stepping stone to eventually understanding whether the bacteria play a role in reactivating recurrent infections. From previous and current studies, there is no relationship between bacteriology and recurrent infections.

Acute Disease↗

Enlarged tonsils and the effect of tonsillectomy. Characteristics of the dentition and facial skeleton. Posture of the head, hyoid bone and tongue. Mode of breathing.

Associations between craniofacial morphology, its development and growth on the one hand and functional factors on the other hand have been eagerly debated in the literature during the last 20 years. The aim of the present thesis, based on five publications, was to evaluate the effect of enlarged tonsils and tonsillectomy on the dento-facial morphology, the posture of the head, the position of the hyoid bone and tongue, and on the mode of breathing. The material comprised 146 Swedish children (66 boys and 80 girls), 5.3-17.3 years old, with a mean age of 10.1 years. Of these children 73 were judged by one otolaryngologist to have enlarged tonsils and were, on this criterion, selected for the investigation. The remaining 73 children comprised the control group and matched the tonsil group for sex and age. The controls were nosebreathers and had no history or symptoms of Ear-Nose-and-Throat-problems. During the investigation 18 of the tonsil children underwent tonsillectomy and 29 remained unoperated. Comparisons between the groups were based on anamnestic and clinical records, measurements on plaster study models and lateral skull radiographs. The results indicate that the children with enlarged tonsils, when compared with the control children, had retroclined lower incisors, protruded upper incisors, shorter lower dental arch, smaller overbite, larger overjet and a greater incidence of lateral crossbites. Furthermore they had retrognathic, posteriorly inclined mandibles, larger anterior lower facial height and skeletal open bite. They also displayed extended headpostures, low posture of the hyoid bone, anterio-inferior posture of the tongue and large oro-pharyngeal depth. 62.5% of the children in the tonsil group were mouthbreathers during the day and 84.7% during the night. The effect of tonsillectomy was mainly associated with a dorsal reposturing of the base of the tongue, change in hyoid bone posture cranially and change to nosebreathing during the night. Furthermore, a decrease in lower inter-molar width and in the tendency to lateral crossbite, as well as a slight increase in the posterior lower facial height had occurred postoperatively. Associations between postural and functional changes mutually, as well as between these changes and morphological changes were found. Enlarged tonsils thus seem to be associated with a characteristic postural and functional pattern, which in its turn seems to have had some influence on the dentition and craniofacial morphology.

Adolescent↗

[Immunomorphologic characteristics of the tonsils and their lymph nodes in human fetuses].

This study was carried out having in view our inadequate knowledge of immunological parameters of human normal tonsils. The purpose of the study was to investigate the development of basic morphological and immunological parameters of organs constituting the functional complex, i. e. palatine, pharyngeal, lingual tonsils and neck lymph nodes that drain them, in human fetuses. Altogether 50 palatine, 31 pharyngeal, 16 lingual tonsils and neck lymph nodes of human fetuses (14 to 32 weeks) were examined. The development and morphology of tonsils as well as the time of lymphocyte settlement were investigated. The pattern of lymphocyte differentiation was studied immunologically. In terms of expression of surface markers, the heterogeneity of T- and B-cell immunity systems and their kinetics in the course of embryogenesis typical of each organ under study were identified. In the complex of organs combined by immune functions, neck lymph nodes can be identified as the pool of T-cells the amount of which makes the total number of the cells in all tonsils. As to B-cells, tonsils contained predominantly EAC-RFC. When compared to tonsils, lymph nodes contained the least quantities of B-lymphocytes.

Adenoids↗

[The palatal tonsils as a part of the lymphatic system. Inflow and outflow of newly-formed lymphocytes].

Many lymphocytes continuously migrate from one lymphoid organ to another. The tonsils are also included in the migratory stream of long-lived lymphocytes. We investigated the question whether newly formed lymphocytes, for example, those produced in the spleen or mesenteric lymph nodes, also migrate to the tonsils and to which compartment. The spleen and mesenteric lymph nodes of normal young pigs were selectively labelled with the DNA precursor 3H-thymidine and one day later smears and sections of the tonsils were autoradiographed. About 1% of all spleen-derived young lymphocytes and about 0.5% of all emigrated mesenteric lymph node lymphocytes were found in palatine tonsils. These were almost exclusively small to medium sized lymphocytes. These cells were mainly found in the interfollicular area around high endothelial venules. Surprisingly high numbers were also located in the reticular epithelium of the crypts, in the corona and even in follicles. In a second series of experiment palatine tonsils were selectively labelled by multiple minute injections of 3H-thymidine. The follicles showed a very high labelling index but labelled lymphocytes were also identified in other compartments. One day later tonsil-derived lymphocytes were found in the spleen and lymph nodes. There is thus a continuous exchange of newly formed lymphocytes between the tonsils and other lymphoid organs.

Animals↗

Investigation of pseudorabies virus DNA and RNA in trigeminal ganglia and tonsil tissues of latently infected swine.

Pseudorabies virus (PRV) nucleic acids in the trigeminal ganglia and tonsils of swine latently infected with the virus were analyzed. By use of DNA-polymerase chain reaction (PCR), 14 of 14 trigeminal ganglia and 12 of 14 tonsils were positive for PRV genomes. By use of RNA-PCR, RNA containing the large latency transcript splice junction were detected in 4 of 4 trigeminal ganglia and 4 of 5 tonsils. In general, results of both PCR procedures indicated that the amounts of PRV DNA and RNA per microgram of cellular nucleic acids were higher in trigeminal ganglia than in tonsils. Identification of peripheral tissues that harbor latent PRV is an important asset for PRV research. The presence of large latency transcript in tonsil tissues, in the absence of virus replication, is a critical characteristic, which indicates that the tonsil is a site of PRV latency. For diagnostic purposes, animals need not be euthanatized to obtain their nervous tissue to determine latency; instead, tonsil biopsy specimens could be obtained from live animals for analysis. For pathogenesis, studies, multiple specimens obtained sequentially from the same animal would be available for examination for the duration of the experiment.

Animals↗

Comparative bacteriology of the surface of normal and pathological palatine tonsils in children.

There are only few studies on the normal bacteriology of tonsils. The purpose of this study was to acquire knowledge about the normal microflora: patients without recurrent tonsillitis (RT) and without tonsil hypertrophy (TH) and to compare these results with the pathological microflora: patients who have recurrent tonsillitis and/or tonsillar hypertrophy. We did 132 cultures of tonsil surface obtained from normal children and 96 cultures from pathological surfaces during the summer and in the winter. Comparing normal and pathological groups, we found Neisseria spp and Enterobacteria spp more frequently in the normal group. There are differences in the surface microflora of tonsils from normal persons and from individuals with tonsillitis.

Adolescent↗

Microanatomical distribution of dendritic cells in normal tonsils.

Lymphoid dendritic cells play an essential role in antigen presentation in primary immune responses and are believed to be important in normal healthy responses of the mucosal immune system. The microanatomical distribution of HLA-DR-positive/S100 antigen-positive dendritic cells was analyzed in 10 normal palatine tonsils. Tonsil biopsies were obtained from 8 normal children undergoing otolaryngological surgery for reasons completely unrelated to tonsil disease. Two samples of normal adult tonsil were also obtained. Standard immunohistochemical methods, with antigen retrieval, were used to detect cell surface markers in formalin-fixed and/or frozen tissue specimens. The clinical identification of these tonsils as normal was confirmed by their microscopic appearance. HLA-DR antigen expression was restricted to lymphocytes, macrophages and dendritic cells; all normal epithelia were negative. S100-positive dendritic cells were readily detected in surface and crypt epithelium and were rare in submucosal sites or follicles. T cells were observed as frequently as dendritic cells in epithelial sites. Dendritic cell density was highest in extrafollicular T cell areas, where CD4-positive lymphocytes were especially abundant. A significant correlation was observed between the total number of different bacterial species isolated from individual normal tonsils and the frequency of dendritic cells in both the crypt epithelium and extrafollicular T cell areas. The number of dendritic cells at the tonsil surface was not similarly related to the bacterial flora.

Child↗

[Beta-lactamase-producing bacteria in recurrent childhood tonsillitis].

Beta-lactamase production by the normal pharyngeal flora could account for the failure of penicillin treatment in patients with recurrent tonsillitis. We studied the microbial flora of tonsils from 22 healthy children (control group) and from 40 children with recurrent tonsillitis who were treated with penicillin. Cultures were made before treatment and repeated 15 days after the first culture. Streptococcus pyogenes was recovered in 25% of the patients in the recurrent tonsillitis group. Beta-lactamase producing bacteria were recovered in 100% of children with tonsillitis and in 86.4% of the healthy children. We found a 65% failure rate of penicillin therapy in recurrent tonsillitis. Our results suggest that beta-lactamase production by pharyngeal organisms does not fully explain the failure of penicillin therapy for recurrent tonsillitis.

Adolescent↗

S-100 protein-positive dendritic cells and CD34-positive dendritic interstitial cells in palatine tonsils.

Dendritic cells (DCs) are effective antigen-presenting cells and have been shown to mature from precursor CD34-positive stromal cells (dendritic interstitial cells, DICs) or monocytes. To gain insight into the local immune response in human tonsils, we investigated immunohistochemically the presence of DCs and DICs in 17 non-hyperplastic and 13 hyperplastic tonsils. Dense infiltrates of S-100-positive DCs were noted in the majority of hyperplastic tonsils, while there were fewer in non-hyperplastic tonsils. DICs were noted specifically at the periphery in the dense hemi-capsule cap that separates the tonsil from the underlying muscle. In addition, their small number suggests that the accumulation of S-100 dendritic cells in hyperplastic palatine tonsils is achieved through migration from other sites rather than through maturation from precursors locally.

Adult↗

Morphology and immunology of the human palatine tonsil.

At the surface of the respiratory and digestive organs the organism first comes into contact nasally and orally with various foreign agents and substances in the air and in food. The palatine tonsils are located at the centre of this strategic region. Immunological processes, both humoral and cellular, are initiated in the different specialised compartments of the palatine tonsils, such as the crypt epithelium, lymphoid follicles and extrafollicular region. Each compartment has a typical composition of lymphocytes and dendritic cell subsets. This review summarises current data on the anatomy, histology, and pathology of the human palatine tonsils, describes their fundamental immunological functions, and provides insight into the various interactions involved in the initiation of immune responses. The palatine tonsil is the only easily accessible human lymphoid organ and is often taken as an example for lymphoid organs. Although affections of the palatine tonsils constitutes an essential part in the clinical routine, it is still controversial whether tonsillectomy is of general benefit. This is of increasing importance since it has been discovered in the last few years that the palatine tonsils are reservoir and replication sites of HIV.

Humans↗

Comparison of histology between recurrent tonsillitis and tonsillar hypertrophy.

To elucidate the aetiology of tonsillar hypertrophy and recurrent tonsillitis, it is important to determine whether a difference exists between these two conditions in microanatomical architecture. The aim of this study was to investigate the difference in follicle size and numbers in tonsils for patients with tonsillar hypertrophy and recurrent tonsillitis using an image analysis method. Our results showed that there was no significant difference in the mean follicle numbers per counting field (40x magnification) between recurrent tonsillitis (4.5 +/- 2.1) and tonsillar hypertrophy (3.8 +/- 0.5). However, the mean follicle area in the tonsillar hypertrophy group (0.23 +/- 0.02 mm2) is significantly (P < 0.01) larger than in the recurrent tonsillitis group (0.15 +/- 0.02 mm2). Our study demonstrates that tonsillar hypertrophy is characterized histologically by an enlargement of follicles compared with chronic tonsillitis, indicating a hyperplastic condition of lymphoid cells in the germinal centres. It may also explain the difference in aetiology and/or immune defence mechanism underlying these two conditions.

Adolescent↗

Clinical observation of palatine tonsils with IgA nephropathy.

We have previously reported that clinical remission could be achieved by combination therapy consisting of steroid pulse therapy and tonsillectomy in patients with IgA nephropathy. However, there is no consensus as to the indications for tonsillectomy in IgA nephropathy (IgAN) patients. To clarify whether there is any correlation between characteristics of removed palatine tonsils and clinical remission rate, we evaluated the relationships between the remission rate of urinary abnormalities and characteristics of 186 IgAN patients (aged 11-65 years) with mild or moderate renal pathology and their tonsils. Remission of proteinuria was observed in 134 patients (72%) and remission of hematuria was observed in 111 patients (60%). There was no significant difference in remission rate of either proteinuria or hematuria in terms of the past history of recurrent tonsillitis, episodes of synpharyngitic gross hematuria, pus plugs in the tonsillar lacunae, size of tonsils, age and the results of tonsillar provocation tests. Our findings suggest that it is very difficult to predict the efficacy of tonsillectomy and steroid pulse therapy based on the gross appearance of tonsils, the tonsillar provocation test or clinical episodes of tonsillitis. Moreover, contraindication of tonsillectomy for aged IgAN patients is not always justified.

Adolescent↗