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Effect of daily injections of ACTH on growth and on the adrenal and lymphoid tissues of two strains of immature fowls.

1. The effects of daily injections of ACTH (30 IU/kg) or physiological saline on growth and on adrenal and lymphoid tissues of Rhode Island Red (RIR) and Light Sussex (LS) chickens were compared at 1, 2 and 3 weeks of age. 2. Saline injections retarded skeletal growth in both strains during the 1st week but only affected weight gain in LS birds. 3. Injections of ACTH depressed growth rate, caused adrenal enlargement and deplenished adrenal cholesterol to the same extent in both strains. 4. ACTH caused a greater reduction in bursal size in RIR than in LS birds. Spleen size was reduced by ACTH only in RIR birds. 5. At 2 and 3 weeks the plasma concentrations of corticosterone of RIR birds were greater than those of LS birds. Plasma corticosterone concentrations were within the normal range 24 h after the last injection of ACTH in both strains. 6. Plasma concentrations of growth hormone was unaffected by ACTH treatment in RIR birds, but it was increased in LS birds after 3 weeks of treatment.

Adrenal Glands↗

Catecholaminergic nerve fibers in bronchus-associated lymphoid tissue: age-related changes.

Age-related changes of the catecholaminergic nerve fibers of the trachea, bronchial smooth muscle, lung capillaries and bronchus-associated lymphoid tissue (BALT) were studied in male Wistar rats aged 3 months (young), 12 months (adult) and 24 months (old/aged). Catecholamine histo- and immuno-fluorescence techniques were used, associated with image analysis and high pressure liquid chromatography with electrochemical detection of nor-epinephrine (nor-adrenaline). In young rats, blue-green fluorescent nerve fibers supply the trachea-bronchial smooth muscle and tracheal and bronchial glands. These structures are innervated by a delicate network of nerve fibers, being rich in varicosities. Pulmonary capillaries are sparsely innervated. The highest nor-epinephrine concentration was found in the trachea and bronchi, followed by BALT. The density and the pattern of noradrenergic nerve fibers of the trachea-bronchial tree or of the pulmonary vessels were similar in young and adult rats. In aged rats, a loss of noradrenergic nerve fibers, involving primarily the supply to the smooth muscle of the trachea-bronchial tree, was observed. Fluorescence microscopic techniques demonstrated a higher sensitivity than nor-epinephrine assay in detecting changes of the sympathetic nerve supply of the trachea-bronchial tree, pulmonary vessels and BALT. The possible significance of reduced noradrenergic nerve supply of the trachea-bronchial-pulmonary tree in aged rats is discussed.

Aging↗

l-selectin and alpha4beta7 integrin, but not ICAM-1, regulate lymphocyte distribution in gut-associated lymphoid tissue of mice.

BACKGROUND: Adhesion molecules on lymphocytes ( l -selectin and alpha4beta7) and endothelium (MAdCAM-1 and ICAM-1) direct lymphocytes into the gut-associated lymphoid tissue (GALT) of mice. Parenteral nutrition and MAdCAM-1 blockade reduce GALT cell mass. This study examined the effects on GALT cell mass of blockade of l -selectin, alpha4beta7, and ICAM-1 with saturating doses of monoclonal antibodies. METHODS: In experiment 1, l -selectin and alpha4beta7 expression were measured by flow cytometry in chow-fed mice. In experiment 2, 49 mice randomly received chow, parenteral nutrition, chow + intravenous (IV) anti-CD62L, chow + IV anti-LPAM-1, or chow + IV isotype control antibody. After 4 days, lymphocyte yields in GALT and respiratory and intestinal IgA levels were measured. In experiment 3, 27 mice randomly received chow, parenteral nutrition, chow + IV anti-ICAM-1 monoclonal antibody, or chow + IV isotype control antibody for 5 days. Lymphocyte counts and IgA levels were determined as in experiment 2. RESULTS: Some 80% of all circulating lymphocytes were positive for l -selectin and alpha4beta7. Lymphocyte counts in the Peyer's patches, lamina propria, and intraepithelial space were lower in the l -selectin and alpha4beta7 blockade groups (3.1, 1.8, and 0.9 x 10(6) and 2.1, 1.9, and 0.7 x 10(6) , respectively) than in the chow group (5.9, 3.0, and 1.7 x 10(6) ; P < .02 vs the l -selectin group and P <.001 vs the alpha4beta7 group) and similar to the levels in the parenteral group. Respiratory and intestinal IgA levels are maintained in all groups except the parenteral group ( P <.04 vs the chow group). ICAM-1 blockade did not influence cell counts or IgA levels. CONCLUSION: Most circulating lymphocytes have GALT homing potential. Their distribution into GALT is hindered by blockade of l -selectin or alpha4beta7, but not by ICAM-1.

Animals↗

Changes in the rat lymphoid tissues after Leydig cell destruction by ethane-1,2-dimethanesulphonate.

Since ethane-1,2-dimethanesulphonate (EDS) causes Leydig cell destruction which may elicit an immune response the lymphoid tissues of sexually mature male rats were examined after an intraperitoneal injection of EDS. The changes observed in the testicular regional lymph nodes confirm an immune response while those observed in the thymus may indicate involvement in the immunological response or be a toxic reaction to EDS.

Animals↗

Distribution of cells bearing the Tac antigen during ontogeny of human lymphoid tissue.

The monoclonal antibody anti-Tac, which binds to the interleukin 2 (IL 2) receptor, was used to identify this antigen in human fetal and adult lymphoid tissue. Liver, spleen, thymus, lymph node, and peripheral blood were examined for Tac-positive cells with the use of frozen sections or cytocentrifuge preparations. The results show that cells in the fetal and neonatal thymus express the Tac antigen; these cells are predominantly located in the medulla. The liver and spleen of both fetus and adult exhibit very few Tac-positive cells. Double staining demonstrates that cells bearing the Tac-antigen stain with Leu-4, an anti-T cell antibody. In adult lymph node tissue, the Tac-bearing cells are predominantly distributed in the interfollicular area, with positive cells also present in the germinal center and mantle zone. The Tac antigen is present on both T and B cells. Few Tac-positive cells are present in the circulating peripheral blood.

Adult↗

Specific transcription of the unrearranged TCR V beta 8.2 gene in lymphoid tissues occurs independently of V(D)J rearrangement.

A truncated T cell receptor (TCR) V beta 8.2 polypeptide expressed on the surface of a precursor lymphoid cell line and on a subset of mesenteric lymph node cells has previously been shown to be encoded by transcripts from unrearranged V beta 8 genes. Germline V beta 8 transcription has now been demonstrated in multiple lymphoid and non-lymphoid tissues in mice of varying ages and in cultured cell lines by reverse transcription-polymerase chain reaction (RT-PCR). Significant levels of V beta 8 germline transcription were found in thymus, spleen, liver and bone marrow and in all lymphoid cell lines studied. Germline V beta 8 transcription in the liver dropped as mice aged, and increased in the bone marrow. Germline V beta 8 transcription was also detectable in thymus, spleen, liver and bone marrow of RAG-1-/- mice. This indicated that it is not dependent upon the presence of mature lymphoid cells, nor necessarily related to V(D)J rearrangement events. Semi-quantitative polymerase chain reaction (PCR) and hybridization with oligonucleotides specific for V beta 8.1, 8.2 and 8.3 showed that the V beta 8.2 gene produced at least 90% of all the germline V beta 8 transcripts in all of the tissues examined. The significance of these results in lymphoid cell development and for models of the regulation of V(D)J rearrangement are discussed.

Alternative Splicing↗

Immunological consequences of intestinal helminth infections in C57BL mice. The effects on lymphoid tissue and reticuloendothelial function.

The characteristics of primary Nematospiroides dubius, mouse-adapted Nippostrongylus brasiliensis and Trichuris muris infections in C57BL mice and their broad effects on lymphoid tissue and reticuloendothelial function have been compared in an attempt to identify correlations between the effects of the parasites and common features of their life cycles. All three parasites increased the size of the spleen and mesenteric node, roughly in proportion to the intestinal worm burden. N. brasiliensis and T. muris caused thymic atrophy, which was not evident with N. dubius even when it was administered intravenously (i.v.) to establish a tissue migration phase. N. brasiliensis accelerated the clearance of I125-labelled polyvinyl pyrrolidone (I125-PVP) from the circulation by increasing uptake by the liver and lungs. N. dubius caused similar increases when given i.v., suggesting that macrophages in these organs are activated by migrating larvae, but did not affect the levels of I125-PVP in circulation. An established intestinal N. dubius infection increased the levels in circulation and in peritoneal cells.

Animals↗

Distribution of laminin variants and their integrin receptors in human secondary lymphoid tissue. Colocalization suggests that the alpha 6 beta 4-integrin is a receptor for laminin-5 in lymphoid follicles.

Laminins are a family of multifunctional basement membrane glycoproteins. Over the last years, many laminin isoforms have been characterized, which were shown to be composed of distinct combinations of variant alpha, beta and gamma chains. Some of these isoforms show remarkable tissue specificity, which suggests functional involvement in local processes. In this study the previously described mAb 4C7, which recognize epithelial basement membranes as well as endothelial basement membranes in lymphoid follicles, was identified as an anti-laminin-5 antibody. Using a set of mAbs against various variant laminin chains we established that specifically the gamma 2 chain of laminin-5 was confined to the endothelial basement membranes of vessels in lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid follicles, whereas other variant laminin chains were also expressed elsewhere in the lymphoid tissue. Additionally, the expression of the known integrin receptors of laminin-5 was also examined. The alpha 6 beta 4 integrin-receptor for laminin was found to be colocalized with the laminin-5 gamma 2 chain on the abluminal surface of endothelial cells, whereas the alpha 3 integrin chain could not be detected in lymphoid follicles. This finding suggests that the alpha 6 beta 4 integrin (and not the alpha 3 beta 1 integrin) serves as a laminin-5 receptor on endothelial cells in the follicular compartment of lymphoid tissue. Furthermore, alpha 6 beta 4 was also found in the same punctuated pattern on FDCs as laminin-5. The function of the laminin-alpha 6 beta 4 complex in this particular localisation is still obscure, but a role in the maintainance of the follicular compartment via hemidesmosome-like attachment sites is postulated.

Antibodies, Monoclonal↗

Expression of Bcl-2 protein and Bcl-2 mRNA in normal and neoplastic lymphoid tissues.

The bcl-2 gene is a unique proto-oncogene that blocks apoptosis; its product is localized on the inner mitochondrial membrane. In non neoplastic human lymphoid tissues, bcl-2 protein is strongly expressed in the small recirculating lymphocytes of the follicular mantle zone; it is expressed less intensely in T-cell areas, and is almost absent from germinal center cells. Bcl-2 mRNA, in contrast to bcl-2 protein, is strongly expressed on most of the latter cells, a similar phenomenon also being observed in peripheral blood lymphocytes (PBL). Resting PBL express both bcl-2 mRNA and protein, while most lymphoblasts in mitogen-stimulated PBL cultures lose bcl-2 protein and become apoptotic, despite expressing higher levels of mRNA. Posttranscriptional regulation of the bcl-2 gene may cause this paradoxical down-regulation of bcl-2 protein and may play an important role in the clonal selection of lymphocytes. Bcl-2 protein is frequently expressed in follicular lymphomas bearing the t(14;18) chromosomal translocation, but it is also widely expressed in many other B- and T-cell lymphomas without bcl-2 rearrangement, showing that mechanisms other than t(14;18) translocation may deregulate bcl-2 expression. Many lymphoid and myeloid cell lines also express bcl-2 protein with no correlation being shown with differentiation stage. Thus, it is conceivable that bcl-2 protein may play a role in the oncogenesis of many hematolymphoid malignancies by interfering with programmed cell death, in concert with other oncogenes or tumor suppressor genes.

Cell Line↗

Mucosa-associated lymphoid tissue lymphoma presented as diffuse swelling of the parotid gland.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct subtype of lymphoma. Parotid MALT lymphoma is a rare tumor that is hard to diagnose by fine-needle aspiration cytology. Therefore, partial parotidectomy is often required for a pathological diagnosis. We report a case of MALT lymphoma presented as unilateral diffuse swelling of the parotid gland, who was diagnosed by partial parotidectomy and underwent radiotherapy.

Biopsy, Fine-Needle↗

Senescence-associated decline of lymphocyte migration in gut-associated lymphoid tissues of rat small intestine.

Scenescence-induced changes in gut-associated lymphoid tissues may contribute largely to the impaired immune responses during aging. Age-related changes in lymphocyte recirculations were investigated in Peyer's patches of rat small intestine. Cell dynamics of labeled T lymphocytes were observed under an intravital fluorescence microscope and compared between young and aged rats. Lymphocyte transport through intestinal lymph was decreased in aged rats. The lymphocyte rolling and adherence in postcapillary venules (PCV) of Peyer's patches was also significantly impaired in aged rats, with decreased expression of L-selectin on lymphocyte surfaces. Immunohistochemical analysis revealed a significant decrease in the CD8-positive cell population in Peyer's patches of the aged group, although mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression in postcapillary venules was unaltered. Lymphocyte adoptive-transfer studies indicated that although both the donor and recipient factors influence the adherence of T cells, the former may play a predominant role in the age-related change. This study clearly demonstrated in situ that T cell migration into Peyer's patches is significantly decreased in the aged intestine, which may reflect the impaired immune responses in the aging process.

Adoptive Transfer↗

Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP).

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common type of lymphoma arising in various tissues throughout the human body. Currently, there is no standard chemotherapy for advanced stage MALT lymphoma. This has prompted us to retrospectively analyse our experience with the MCP regimen (mitoxantrone, chlorambucil and prednisone) in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with histologically verified MALT lymphoma undergoing chemotherapy with MCP were evaluated retrospectively. The MCP regimen consists of mitoxantrone 8 mg/m(2) intravenously on days 1 and 2, chlorambucil 3 x 3 mg/m(2) per os (p.o.) on days 1-5 and prednisone 25 mg/m(2) p.o. on days 1-5. Information analysed included localisation of the lymphoma, clinical stage, pretreatment, number of chemotherapy cycles administered, toxicity, response to treatment, follow-up time, relapse and survival. RESULTS: A total of 15 patients (six females and nine males aged between 34 and 88 years) with histologically ascertained MALT lymphoma undergoing treatment with the MCP regimen were identified from our records. Ten patients had extragastric lymphoma, while five patients suffered from gastric MALT lymphoma. All patients were chemotherapy-naïve, while two had been locally irradiated before application of MCP for recurrent disease. A total of 74 cycles was administered to our patients, with a median number of five cycles per patient. Eight (53%) patients achieved complete remission, six (40%) patients partial response and only one (7%) patient had progressive disease. Subjective tolerance was excellent, and toxicities were mainly haematological, including granulocytopenia World Health Organisation grade 3 and 4 in three patients each. In two patients, this was accompanied by single episodes of uncomplicated herpes simplex infection. At the time of analysis, all patients are still alive. No relapses have occurred after a median follow-up time of 16 (range 12-29) months. CONCLUSIONS: Our data suggest that MCP is an effective and well-tolerated regimen for treatment of patients with MALT lymphoma irrespective of localisation. Judging from our data, MCP also appears to be a feasible regimen in elderly patients.

Administration, Oral↗

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the thymus: report of four cases.

Mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus is extremely rare, and little is known about its clinicopathological features. In this study, we examined four cases of MALT lymphoma in the thymus at our institute in terms of clinicopathological features. Most patients had autoimmune disease or hyperglobulinemia, and they also had cysts in the tumors. Both elevated serum levels of autoantibodies and the polyclonal increase in serum Ig remained almost unchanged after total thymectomy in all patients. We recommend that MALT lymphoma in the thymus should be considered in the differential diagnosis when a cystic thymic mass is found and if the patient is Asian and/or has autoimmune disease or hyperglobulinemia.

Adult↗

Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of Helicobacter pylori.

BACKGROUND: Lymphoma of the mucosa associated lymphoid tissue (MALT) arising in the stomach has been shown to be related to Helicobacter pylori infection, and total regression of gastric lymphoma after successful eradication of H pylori has consistently been reported. MALT-type lymphoma at other localisations, however, has to our knowledge not been linked to H pylori, and eradication of the bacteria has not been studied for management of such lymphomas. PATIENT/METHOD: A 67 year old man was diagnosed with MALT-type lymphoma simultaneously involving the stomach and the colon descendens. In addition to the presence of MALT-type lymphoma, H pylori associated chronic gastritis was diagnosed, and treatment with clarithromycin, metronidazole, and omeprazole was initiated, resulting in its successful eradication. RESULTS: Follow up performed four months later showed regression of the colonic manifestation, whereas the gastric lymphoma did not respond to antibiotic treatment, as assessed by regular follow up for 14 months, in spite of its restriction to mucosa and submucosa. The patient was therefore treated with oral cyclophosphamide (100 mg a day) resulting in partial remission after seven months of continuous treatment. Because of the presence of residual lymphoma, additional irradiation was performed, which led to complete remission of the gastric lymphoma. The patient remains in complete remission 40 months after diagnosis and 26 months after initiation of treatment. CONCLUSION: In the case of concurrent gastric and intestinal low grade MALT-type lymphoma, H pylori eradication may cause regression of the intestinal lesion.

Aged↗

S-100-immunoreactive giant macrophages in lymphoid tissues of the guinea pig.

Giant cells containing S-100 protein of the lymphoid tissues in the guinea pig were studied by immunohistochemistry using S-100 antiserum. S-100-immunoreactive giant cells were dendritic in shape, contained one or two irregular-shaped, euchromatic nuclei, phagosomes of various diameter, numerous mitochondria and microfilaments in the perikaryon, and extended cell processes free of cell organelles. These cells predominantly lined the superficial cortex facing the subcapsular sinus, were less numerously scattered in the medulla of lymph nodes and located at the marginal zone of the spleen. They also stained with S-100 alpha monoclonal antiserum and showed active phagocytosis for aldehyde-fixed red cells or colloidal carbon in the popliteal lymph node and spleen. S-100-immunoreactive giant cells also appeared in the corticomedullary zone of the thymus and in the interfollicular area of the Peyer's patches of the gut. Small sinus macrophages, which exhibited active phagocytosis for colloidal carbon but were less active for red cells in the popliteal lymph node and spleen, were not stained with S-100 antiserum. These findings indicate that S-100-immunoreactive giant cells of the lymph node and spleen are a subpopulation of macrophages different from S-100-negative cells of the small type.

Animals↗

T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10.

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multistep process and can be clinico-pathologically divided into Helicobacter pylori-associated gastritis, low-grade tumors, and high-grade tumors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(11;18)(q21;q21) and t(1;14)(p22;q32) has provided fresh insights into the pathogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transcript between the API2 and the MALT1 genes, whereas t(1;14) (p22;q32) causes aberrant nuclear BCL10 expression. Significantly, nuclear BCL10 expression also occurs frequently in MALT lymphomas without t(1;14)(p22;q32), suggesting an important role for BCL10 in lymphoma development. Thirty-three cases of H pylori gastritis, 72 MALT lymphomas, and 11 mucosal diffuse large B-cell lymphomas (DLBCL) were screened for t(11;18)(q21;q21) by reverse transcription-polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2--MALT1 fusion transcript was not detected in H pylori gastritis and mucosal DLBCL but was found in 25 of 72 (35%) MALT lymphomas of various sites. Nuclear BCL10 expression was seen in 28 of 53 (53%) of MALT lymphomas. Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%). Furthermore, t(11;18)(q21;q21) closely correlated with BCL10 nuclear expression. These results indicate that both t(11;18)(q21;q21) and BCL10 nuclear expression are associated with advanced MALT lymphoma and that their oncogenic activities may be related to each other. (Blood. 2001;98:1182-1187)

Adaptor Proteins, Signal Transducing↗

Molecular pathogenesis of mucosa-associated lymphoid tissue lymphoma.

Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occur in a number of anatomic sites, but share overlapping morphologic and immunophenotypic features. Helicobacter pylori infection has been identified as an etiologic factor in gastric MALT lymphoma, and a growing list of other infectious organisms have recently been shown to be associated with MALT lymphomas at other anatomic sites. Although cause and effect has not been established for most of these infectious agents, our understanding of the biology has significantly improved, in part through the application of standard cytogenetic analyses. The common karyotypic alterations that characterize MALT lymphomas include the trisomies 3 and 18, the translocations t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), t(3;14)(q27;q32), and the recently described t(3;14)(p14.1;q32). This apparent complexity of cytogenetic alterations that have now been implicated in the pathogenesis of extranodal MALT lymphoma serves as a paradigm for molecular cross talk in neoplastic disease. Recent data have shown that at least three of the disparate translocations affect a common signaling mechanism, and thus unify all three under a common pathogenesis, resulting in the constitutive activation of the nuclear factor kappa B (NF-kappaB) pathway. It may be that the new MALT-related translocation involving the FOXP1 gene and other as yet undiscovered translocations may all have in common increased NF-kappaB signaling.

Adaptor Proteins, Signal Transducing↗

Morphometry of normal human lymphoid tissues. Nuclear invaginations and clefts.

We performed morphometric analysis on samples of human lymphoid tissue involved by reactive hyperplasia to assess the basis for the concept of cleaved lymphocyte nuclei in current non-Hodgkin's lymphoma classification. Histologic sections from all regions of lymph node showed considerable variation (usually 9% to 16%) in the proportion of nuclear profiles, with invaginations of at least 0.4 micron. Invaginations sufficiently deep to label nuclear profiles as "cleaved" occurred in 2% or less of lymphocytes of all regions seen on 1-micron plastic-embedded sections. The majority of nuclear invaginations were less than 1.6 micron deep. Analysis of the morphometric data suggests that the nuclei of germinal center lymphocytes undergoing antigen-induced transformation do not progress through a specific phase in which they become increasingly cleft. With the increased angularity and irregularity of lymphocyte nuclear profiles in germinal centers, the "cleaved" appearance of these nuclei in paraffin-embedded sections seems to be due to linear creases and overlapping segments of the nucleus.

Adolescent↗