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[A brief outline of the evolution of lymphoid tissue and its immunocellular reactivity in vertebrates].

The steps of the phylogenetic development of the lymphoid tissue and its immunolcellular reactivity were studied. It was shown that a gradual change from lymphoid multifunctional cells disposed diffusely in primitive lower vertebrates to the concentration of lymphoid cells into complicatedly arranged lymph nodes was taking place. Common features and species (group) peculiarities of the structure of the lymphoid tissue and its immunological reactivity were studied. The similar succession of immunocellular reactions has the phagocyte reaction as the first link. Then goes the lymphocyte reaction with a following transformation of lymphocytes to blasts and their further differentiation and proliferation into young forms of cells of the plasmocyte row. The antibody-forming cells were found in all the vertebrates studied and their morphology was under research. Species peculiarities of lymphoid cells and their immunoreactivity were studied.

Animals↗

The differential expression of Galectin-1 and Galectin-3 in normal lymphoid tissue and non-Hodgkin's and Hodgkin's lymphomas.

The WHO classification of lymphomas was established on the basis of clinical, morphological, immunohistochemical and genetic criteria. However, each entity displays its own spectrum of clinical aggressiveness. Treatment success varies widely and is not predictable. Since galectins are involved in oncogenesis and the physiology of immune cells, we investigated whether galectin-1 and galectin-3 immunohistochemical expression could differ in 25 normal lymphoid tissues, 42 non-Hodgkins and 14 Hodgkins lymphomas. Immunohistochemical galectin expression was submitted to semi-quantitative and quantitative (computer-assisted microscopy) evaluations. This study is completed by an analysis (by means of quantitative RT-PCR) of galectin-3 mRNA expression in 3 normal lymph nodes, 3 follicular lymphomas (FLs) and 3 diffuse large B-cell lymphomas (DLBCLs). The data show that in normal lymphoid tissue, lymphocytes do not express galectin-1 and rarely express galectin-3. In contrast, galectin-3 was expressed in 8 of the 16 DLBCL cases and in 1 of the 8 FL cases. Furthermore, galectin-3 mRNA was expressed 3 times more in the DLBCLs than in the FLs. While the blood vessel walls of the lymphomas expressed galectin-1, the vessel walls of normal lymphoid tissues did not. This expression of galectin-1 in blood vessel walls was correlated with vascular density. The present study thus shows that DLBCL can be distinguished from normal lymphoid tissue and other lymphomas on the basis of galectin-3 expression.

Galectin 1↗

Localization of beta 1 integrins and their extracellular ligands in human lymphoid tissues.

In this study, we describe the immunocytochemical distribution of the beta 1 integrins (alpha 1 to alpha 6) and their extracellular matrix ligands in human peripheral lymphoid tissues. The results show that within these tissues individual beta 1 integrins are differentially expressed by (sub)populations of stromal cells, including reticular cells, endothelial cells, epithelial cells, and sinus lining cells. The extracellular matrix components studied, eg, collagen I, III, and VI, fibronectin, laminin, and vitronectin, were predominantly associated with the stroma of the lymphoid tissues, and a unique distribution pattern was observed for each of them. Except for alpha 4 (and beta 1), low or no expression of the beta 1 integrins was found on lymphocytes, macrophages, interdigitating cells, and follicular dendritic cells. The results suggest that cell-matrix interactions play a major role in the maintenance of the complex spatial organization of the lymphoid tissue.

Child↗

Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori.

Regression of low-grade B cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori with antibiotic therapy was recently shown in a small number of patients with low-volume tumors. A patient with a > 10 cm nodular gastric mucosa-associated lymphoid tissue lymphoma that caused hematemesis and weight loss is described. Antibiotic therapy of H. pylori resulted in full clinical recovery and resolution of the mass lesion and morphological features of lymphoma on routine histological examination. However, monotypic immunostaining of plasma cells persisted in a separate and grossly normal-appearing region of the stomach. Antibiotic therapy may be of benefit in patients with mucosa-associated lymphoid tissue lymphoma with mass lesions and significant signs and symptoms, but periodic search for residual lymphoma is needed.

Female↗

Primary gastric lymphoma--a tumour of mucosa-associated lymphoid tissue. A histological and immunohistochemical study of 36 cases.

A series of 36 cases of non-Hodgkin's lymphoma of the stomach have been analysed using routine histological techniques and immunohistochemistry. All cases were categorized as follicle centre cell lymphomas. Apart from two cases who had nodal lymphomas followed by gastric lymphomas, all cases appeared to represent primary lymphoma of mucosa-associated lymphoid tissue. It is proposed that the morphology and behaviour of these tumours reflect their origin from gut-associated lymphoid tissue. Physiologically well-differentiated examples show monotypic plasmacytic differentiation. Infiltration of gastric glands by follicle centre cells forming characteristic lympho-epithelial lesions is, we believe, a pathognomonic feature of primary gastric lymphoma. The spread of these tumours is within the mucosa-associated lymphoid tissues involving, in particular, the nasopharynx and lung but seldom spreading to peripheral lymph nodes or bone marrow. This concept of gastric lymphomas as primary neoplasms of gut-associated lymphoid tissue has important implications with respect to the investigation and treatment of this disease.

Adolescent↗

Immunohistochemical localization of smooth muscle myosin in human spleen, lymph node, and other lymphoid tissues. Unique staining patterns in splenic white pulp and sinuses, lymphoid follicles, and certain vasculature, with ultrastructural correlations.

The anatomic distribution of smooth muscle myosin, a contractile protein, was determined in a variety of lymphoid tissues (spleen, lymph nodes, tonsils) with the use of highly specific rabbit antibodies to human uterine smooth muscle myosin and an indirect immunoperoxidase technique. In the spleen, in addition to the anticipated immunoreactivity in the walls of arteries, veins, splenic capsule, and trabeculas, other staining patterns were observed. Smooth muscle myosin-containing cells which comprised the adventitia of the trabecular arteries appeared continuous with myosin-containing reticular cells of the white pulp. The latter cells assumed a circumferential pattern within the periarteriolar lymphoid sheaths, then blended delicately with the red pulp at the marginal zone. Ultrastructurally, immunogold techniques demonstrated that smooth muscle myosin in these cells was localized to cytoplasmic filaments. Within the red pulp, a different and distinct staining pattern was observed for the splenic sinuses. Short, regular, orderly, and repetitive bands of immunoreactivity, aligned parallel to the long axis of the sinus, extended between contiguous ring fibers. By immunoelectron microscopy these structures corresponded to distinct bundles of filaments in the endothelial lining cells of the splenic sinuses. Factor VIII associated antigen was also identified in the splenic lining cells in cryostat and paraffin sections, and ultrastructurally. Within the red pulp of the spleen, the sheaths of sheathed capillaries also revealed strong immunoreactivity for smooth muscle myosin. Other sites of immunohistochemical localization of smooth muscle myosin included dendritic reticulum cells present in reactive follicles and in nodular non-Hodgkin's lymphomas. Certain vascular structures, specifically sinus lining cells and Schweigger-Seidel capillary sheaths of the spleen and postcapillary venules of lymph nodes and tonsils, coexpressed smooth muscle myosin and Factor VIII associated antigen. The patterns of localization of smooth muscle myosin are correlated with anatomic structures and possible tissue functions.

Animals↗

Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma.

Low-grade B-cell bronchial associated lymphoid tissue (BALT) lymphoma is a distinct subgroup of non-Hodgkin's lymphoma. Chronic antigen stimulation, triggered by autoimmune process or persistent infection may precede the development of BALT lymphoma. The lymphoma cells originate from the marginal zone and by invading the bronchial epithelial tissue, give rise to the lymphoepithelial lesion. BALT lymphoma shares the morphologic, immunophenotypic, and cytogenetic characteristics of other mucosa associated lymphoid tissue lymphomas. A majority of the patients are asymptomatic and pulmonary lesions are incidentally discovered on a routine chest radiograph. However, the clinical and radiographic features of BALT lymphoma are nonspecific. The disease is often localized at the time of diagnosis and responds favorably to local treatment, but the optimal management is not clearly defined. Overall, BALT lymphoma has a favorable prognosis and is associated with long-term survival.

Bronchial Neoplasms↗

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in guinea pig lymphoid tissue.

Aryl hydrocarbon hydroxylase (AHH) activity was detected in a variety of guinea pig lymphoid tissues and was increased by intradermal or ip administration of 3-methylcholanthrene AHH levels were generally greater in spleen than in lymph node, bone marrow, or thymus. Similar AHH activities were observed in lymphoid tissues from Sewall-Wright inbred strain 2 and strain 13 guinea pigs. Greater AHH activities were associated with peritoneal and alveolar macrophages than with lymph nodes lymphocytes in the absence of mitogens.

Animals↗

Tonsillar (Waldyer's ring equivalent) lymphoid tissue in the rat: lymphocyte subset binding to high endothelial venules (HEV) and in situ distribution.

We have studied lymphocyte traffic to the Waldeyer's ring equivalent (WRE) lymphoid tissue of the rat, by measuring the in vitro binding of various lymphocyte subsets to high endothelial venules (HEV) in the WRE. In addition, we studied the in situ distribution of these lymphocyte subsets. WRE tissue consists of B and T cell areas; the latter contain HEV. B cells outnumber T cells, and T helper (CD4) cells outnumber T suppressor/cytotoxic (CD8) cells (T/B ratio = 0.7; CD4/CD8 ratio = 5.1). In vitro studies of lymphocyte binding showed that lymphocytes adhere almost equally well to HEV in WRE tissue as to HEV in lymph node (LN) tissue, and much better to HEV in WRE than to HEV in Peyer's patch (PP) tissue. T cells bind better than B cells to HEV in WRE (T/B binding ratio = 1.8), and CD8 cells better than CD4 cells (CD8/CD4 ratio of 2.9-3.2, dependent on cell source). The observed preference of T over B cells in binding to HEV is not reflecting the distribution of these lymphocyte sets in situ. In this respect the WRE takes a unique position, since in other lymphoid organs T/B binding ratios parallels T and B cell distribution in situ. This may suggest a much more rapid passage of T cells through the WRE than through other lymphoid tissues, although other mechanisms cannot be ruled out. The CD8/CD4 binding ratio to HEV in WRE contrasts with situ distribution of these cells also; however, this is found for LN and PP lymphoid tissue too.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dental development and the pharyngeal lymphoid tissue.

Because the teeth are housed and develop within the jaws, skeletal development of the maxilla and mandible is a primary factor in the consideration of any problems pertaining to the developing dentition. Growth of the posterior nasal choanae, the maxilla, and the nasopharynx should be evaluated as a unit in assessing the favorable or unfavorable character of the nasopharyngeal region. Both large and small adenoidal tissues should be examined in light of the morphologic character of the nasopharynx (be it small, large, narrow, or wide) and related to the developing maxilla. Variables in size and location of the maxilla and the pharynx will play an important role in the impact that lymphoid tissue will have on the patency of the nasopharyngeal isthmus. Synchronized growth between the normally developing adenoids and the migration of the maxilla away from the cranial base will produce a balanced environment that precludes nasal obstruction by the presence of adenoids. With time, the changes in spatial relationships between the posterior border of the maxilla and the posterior pharyngeal wall plus atrophy of the adenoidal tissue will generally minimize or eliminate the problems of nasal obstruction and mouth breathing. Growth data may be used to evaluate the status, assess progress, measure comparability, determine inheritance patterns, and confer individuality. Unit-trait inheritance of the teeth, alveolar processes, maxilla, mandible, soft-tissue profile, tongue, pharynx, and lymphoid tissues may well produce more definitive answers to the question of the developing dentition and the pharyngeal lymphoid tissue. Finally, at present, no clinician can categorically state that enlarged tonsils or adenoids per se are responsible for abnormal dentition in the absence of other factors.

Adenoids↗

Prevalence of Helicobacter pylori DNA in recurrent aphthous ulcerations in mucosa-associated lymphoid tissues of the pharynx.

OBJECTIVE: To determine the presence of Helicobacter pylori and, if detected, its potential prevalence in causing recurrent aphthous ulcers confined to mucosa-associated lymphoid tissues of the pharynx. DESIGN: Prospective, controlled clinical trial. SETTING: Otolaryngology Department of Tanta University Hospitals, Tanta, Egypt. PATIENTS: A total of 146 patients with recurrent multiple aphthous ulcers of the oral cavity and pharynx and 20 normal control subjects. INTERVENTIONS: Patients were assigned to group 1 (n = 58), in which the ulcers were strictly limited to the lymphoid tissues, or group 2 (n = 88), in which the ulcers were randomly distributed in the oral cavity and pharynx. Helicobacter pylori DNA was extracted from 3-mm-diameter tissue samples, and polymerase chain reaction amplifications were performed for the 16S ribosomal RNA gene. MAIN OUTCOME MEASURE: Positivity for H pylori. RESULTS: In group 1, 39 patients (67%) were positive for H pylori DNA, while in group 2, 9 patients (10%) were positive (chi(2) test, P<.001). It was not detected in any of the 20 control samples. CONCLUSION: Our results support a possible causative role for H pylori in recurrent aphthous ulcerations with a characteristic distribution and affinity to mucosa-associated lymphoid tissues of the pharynx.

Adolescent↗

Lymphoid tissues targeting of liposome-encapsulated 2',3'-dideoxyinosine.

OBJECTIVE: To improve the pharmacokinetics and lymphoid tissues targeting of 2',3'-dideoxyinosine (ddI) by encapsulation in liposomes. METHODS: The pharmacokinetics and tissue distribution of free and liposome-encapsulated ddI were determined in C57BL/6 mice following intravenous and subcutaneous administration of a single bolus dose (3 mg ddI/kg). RESULTS: Intravenous administration of liposome-encapsulated ddI greatly reduced the systemic clearance of the anti-HIV agent. The elimination plasma half-life of ddI incorporated in 112 and 83 nm liposomes was 46 and 14 times higher than that of the free drug, respectively. The tissue distribution profile of liposomal lipids clearly showed that the use of liposomes allows efficient targeting of lymph nodes and macrophage-rich tissues (spleen and liver) for at least 24 h following intravenous injection. In contrast, the accumulation of liposomes in these tissues was much lower following subcutaneous administration. CONCLUSION: Incorporation of ddI in liposomes greatly improved the pharmacokinetics of the anti-HIV agent after intravenous injection. The use of liposomes could represent a convenient approach to targeting lymphoid tissues. Strategies aimed at improving drug retention within liposomes should further enhance and prolong drug delivery to lymphoid organs.

Animals↗

Demonstration of S-100 protein distribution in human lymphoid tissues by the avidin-biotin complex immunostaining method.

Immunoreactivity for S-100 protein was investigated immunohistochemically in a series of 49 fixed and paraffin-embedded normal, reactive, and neoplastic human lymphoid tissue specimens. The avidin-biotin complex immunoperoxidase method was used, with overnight (12-hour) incubation with a commercially available antiserum to S-100 protein. In addition, cryostat sections were tested with DRC 1 monoclonal antibody to dendritic reticulum cells (DRCs) in three cases and with OKT6 antibody to interdigitating reticulum cells (IRCs) in nine cases. All tissues, including lymph nodes, tonsils, adenoid, spleens, appendices, thymuses, and tissues containing nodular reactive lymphoid infiltrates, demonstrated a consistent immune staining pattern. A striking network composed of dendritic processes that showed finely granular S-100 protein immunoreactivity was observed in most of the follicular germinal centers; a similar dendritic pattern was observed in the follicular centers when the corresponding frozen sections were immunostained with DRC 1. In the extrafollicular areas, the S-100-positive cells topographically and morphologically resembled the IRCs that were demonstrated by OKT6 antibody in the corresponding frozen sections. The results seem to indicate that cells topographically and morphologically similar to IRCs and DRCs in human lymphoid tissues from different sites share immunoreactivity for S-100 protein. The present study confirms the unexpected presence of S-100 protein in dendritic cells of follicular germinal centers by a simple and currently available method.

Antibodies, Monoclonal↗

Pseudo-spikes are common in histologically benign lymphoid tissues.

T cell receptor gene rearrangement is a classic marker of T cell clonality and is a useful adjunct in the diagnosis of T cell lymphomas and leukemias. Rearranged V-J gene segments amplified by polymerase chain reaction (PCR) are traditionally analyzed by polyacrylamide gel electrophoresis. We and others have analyzed TCR-gamma PCR products using capillary gel electrophoresis, which produces single nucleotide resolution and provides improved diagnostic sensitivity over conventional methods. However, with this marked increase in resolution and sensitivity, it is necessary to re-define normal variation of TCR-gamma gene rearrangement in control tissues to allow appropriate interpretation of monoclonality if present. Using DNA capillary gel electrophoresis, we examined the spectrum of normal patterns for TCR-gamma in a variety of T-cell-rich, histologically benign tissue types, including spleen, lymph node, tonsil, and blood, and compared this with the patterns in T cell lymphoma samples. We defined relative peak heights as h1/h2, where h1 represents the peak height of the largest peak above the normally distributed population, and h2 represents the peak height of the normally distributed curve. We found spikes in almost 20% of histologically benign samples with relative peak heights that were more than 0.5 and up to 1.5. We designated these as pseudo-spikes, because they may be mistaken for monoclonal spikes. In contrast, the relative peak height of the T cell lymphoma samples that showed clonal rearrangement was much higher than that of the pseudo-spikes, being at least 2 in 11/11 and at least 3 in 10/11 cases. Our data suggest that peaks with relative height of at least 3 represent a true clonal population in diagnostic samples. Peaks with relative heights of less than 1.5 may be insignificant, while peaks with relative heights between 1.5 to 3 may warrant further evaluation. Although capillary gel electrophoresis is superior in assessing T cell clonality, caution must be exercised when interpreting results, because pseudo-spikes appear to be common in benign tissues with lymphoid populations and are not necessarily indicative of clonal malignant T cell population.

Clone Cells↗

Activation antigen expression on human T cells. I. Analysis by two-colour flow cytometry of umbilical cord blood, adult blood and lymphoid tissue.

Activation antigens (actags) were detected on T cells at low levels of intensity by carefully defining negative cells with a panel of control antibodies. The mean percentage of blood T cells from healthy volunteers that expressed actags were 22% (CD25), 54% (CD26), 38% (CD38), 12% (CD54), 6% (CD69) and 21% (HLA-DR). The variability of actag expression detected by this sensitive method was determined on healthy volunteers by repeated estimation over a year. The percentage of T cells expressing CD25 and CD26 varied no more than repeated estimation of the CD4 T cell subset, whereas other actags showed greater variability. The antigen density of these actags on T cells was determined in relation to CD4 antigen density, and for most actags ranged from 10% to 75% of the level of CD4 antigen density except for CD7 and HLA-DR, which could exceed that of CD4. Different degrees of actag expression characterized T cells from different blood and lymphoid tissues. CD26, CD38 and CD45RA were universally expressed in cord blood at higher antigen density than adult blood. This immature pattern was consistent with recent thymic emigration. CD25, CD45RO, CD54 and HLA-DR progressively increased from cord blood through adult blood to lymphoid tissues, consistent with antigen-driven activation, whereas CD26 and CD45RA decreased. CD69, a very early activation antigen, abruptly increased in lymphoid tissue, exceeding CD25 by two-to-three-fold and suggesting a pre-activation state that may not involve commitment to antigen-driven proliferation. CD7 and CD38 expression was higher in cord blood and lymphoid tissue than in adult blood, indicating both an antigen-independent and -dependent up-regulation.

Adult↗

[Structural and functional organisation of the spleen lymphoid tissue after exposure to hypergravitation].

Using the stereologic methods and quantitative analysis of the cells of lymphoid series in the splenic white pulp of Wistar rats, the changes were studied after continuous 5-day-long exposure to hypergravitation of 2 G. The injurious effect of hypergravitation was manifested in the reduction of the dimensions of periarterial lymphoid sheaths (PALS) and of lymphoid nodules, marginal zone dilatation and the disappearance of lymphoid nodules with germinal centers. Changes in the cell population of the white pulp are indicative of the suppression of blast-transformation and cell reproductive activity (as demonstrated by the disappearance of blast cells and the mitotic cells) and the reduction of lymphocytopoiesis in the organ lymphoid tissue. The proportion of immature plasma cells is increased. The changes demonstrated are more pronounced in PALS than in lymphoid nodules. The significant cellular reorganization of the marginal zones is the reflection of compensatory processes, which develop in response to the injurious effect of hypergravitation on the lymphoid tissue of the spleen.

Animals↗

Expression of the CD30 antigen in non-lymphoid tissues and cells.

Originally, expression of the CD30 antigen was shown to be typical of the tumour cells of Hodgkin's disease (HD) and of anaplastic large cell lymphomas (ALCLs). In reactive lymphoid tissue, CD30 is expressed only in a small population of activated lymphoid blasts. Since then, several reports have been published describing CD30 expression in non-lymphoid tissues and malignancies, such as embryonal carcinomas (ECs), seminomas, cultivated macrophages, two histiocytic neoplasms, decidual cells, and mesotheliomas. As CD30 detection is important in the differential diagnosis of HD and ALCL, the expression of CD30 in different non-lymphoid tissues was re-evaluated by immunohistology and in situ hybridization. Extra-lymphoid CD30 expression was found in 48/51 cases of EC or EC components of germ cell tumours, in decidual cells of 1/10 cases, in activated mesothelium in 16/28 pleural and peritoneal effusions, and in small foci of tumour cells in 2/8 mesotheliomas. CD30 expression was not confirmed in 27 germ cell tumours of the testis without an EC component nor in cultivated macrophages and 17 histiocytic malignancies. The knowledge of these CD30 expression patterns is important for the immunohistological differential diagnosis of anaplastic tumours. The absence of CD30 expression in reactive and neoplastic macrophages does not favour the concept that HD and ALCL are derived from these cells.

Adolescent↗

Distribution of NGF receptors in normal and pathologic human lymphoid tissues.

To identify nerve growth factor (NGF) target cells in normal and pathologic human lymphoid tissues, we have studied the expression of the low-affinity NGF receptor (p75LNGFR) and the high-affinity tropomyosin-related kinase NGF receptor (TrkA). A RNAse protection assay revealed the expression of trk transcripts in thymus, spleen, palatine tonsils and lymph nodes. TrkA immunoreactivity was shown in thymic epithelial cells, cryptic tonsillar epithelium and several monocyte-derived cells including epithelioid and multinucleated Langhans' cells, follicular dendritic cells and interdigitated reticular cells. TrkA immunoreactivity was rarely observed in normal T- and B-lymphocytes, but was intense in lymphoma cells of several B-cell lymphoma subtypes, anaplastic large cell lymphomas and Reed-Sternberg cells. Western blot analysis revealed the presence of p75LNGFR and of p80Trk and glycosylated Trk isoforms (gp110, gp140). p75LNGFR immunoreactivity was detected in epithelial Hassal's bodies, follicular dendritic cells, interdigitated reticular cells, periarteriolar macrophages, endothelial sinusal cells and nerve endings. The broad expression of NGF receptors may be an indicator of neurotrophin activity in lymphoid tissues and suggests their implication in inflammatory or lymphoproliferative disorders.

Antibodies, Monoclonal↗