An immunohistochemical study on the postnatal development of rat nasal-associated lymphoid tissue (NALT)

Summary This study concerns the development of nasal-associated lymphoid tissue in the rat, using immuno- and enzyme-histochemical staining techniques on cryostat sections. Nasal-associated lymphoid tissue is present at birth as a small accumulation of mainly T lymphocytes and non-lymphoid cells; B cells are rare. Distinct areas of T and B cells appear at 10 days after birth; by that time high endothelial venules are also observed. Intra-epithelial lymphocytes are present, most of them being T-helper cells. ED1+ macrophages are seen throughout the tissue. The proportion of ED1+cells does not change during ontogeny. ED2+cells (tissue macrophages) are present predominantly at the border between the lymphoid tissue and the surrounding connective tissue, in all age-groups. ED3+mononuclear cells are scattered throughout the nasal-associated lymphoid tissue of young animals. Later on, the ED3+ cells migrate into the border-area between lymphoid and connective tissue. Ia+ non-lymphoid cells in the nasal lymphoid tissue increase in number during ontogeny. Only a few of them show acid phosphatase activity, indicating that the proportion of classical scavenger macrophages is low. Some of them may be antigen presenting (dendritic) cells. Ia+ dendritic cells also occur between the epithelial cells. Moreover, some epithelial cells express the Ia marker.     

Are all lymphoid blasts in the cell cycle?

Labelling index after one or repeated intravenous injections of 3H-thymidine was measured for various subpopulations of lymphatic cells in different canine lymphoid compartments and correlated with cell morphology. High doses of tritiated thymidine were injected and exposure times of up to 211 days were used. The labelling indices of lymphoid blasts were comparable in all tissues investigated. Labelling index varied from 100% in immunoblasts to 4% in small-sized lymphocytes. Approximately 80% of immunoblasts were labelled 1 h after 3H-thymidine application and 100% labelling was obtained after 12 h repetitive 3H-thymidine labelling. In contrast with mediumsized and large lymphocytes, immunoblasts seem to be rapidly proliferating cells in the dog with almost no G_o cells. Supported by the Deutsche Forschungsgemeinschaft DFG Grant SFB 112     

The fate of intraperitoneally injected carbon particles in cyprinid fish

Summary The lymphoid organs of rosy barb (Barbus conchonius) and carp (Cyprinus carpio) were investigated for their phagocytic uptake of carbon, after its intraperitoneal injection. Carbon handling was similar in both species. It was first detected in the lymphoid organs at 30 min after injection. During the first day, carbon was phagocytized by macrophages situated in the spleen within the ellipsoids and in the red pulp. In head and trunk kidney, carbon was found in macrophages scattered throughout the haemopoietic parenchyma, and in cells lining the blood sinuses. In the spleen, macrophages replete with carbon left the ellipsoidal structures and formed aggregates with pigment-containing macrophages from day 6 onwards. In all lymphoid organs, almost all carbon was ultimately concentrated in the melano-macrophage centres.     

Ultrastructure of the jugular body of Rana pipiens

Summary The jugular bodies in adult Rana pipiens, are surrounded by a capsule of mesothelium and connective tissue, and their parenchyma consists of cell cords arranged in a sinusoidal network. The cell cords are formed by irregular reticular cells, showing numerous filaments and joined together by zonulae adhaerents. The intercellular spaces are filled by reticular fibres and free cells. These latter are small and medium lymphocytes, lymphoblasts, and developing and mature plasma cells. Additionally, free macrophages, neutrophils and acidophils also occur. Sinusoidal blood vessels show thin walls with numerous filaments and pinocytotic vesicles. They exhibit a discontinuous basement membrane, and tight junctions frequently occur between endothelial cells. Occasionally, lymphatic vessels are found and the innervation is principally vasomotor, although nerve endings appear remarkably near reticular cells and lymphocytes. The jugular bodies of adult R. pipiens are plasma cell and antibody-forming organs, whose functional significance is discussed in relation to their ultrastructural organization.     

DISC1-related signaling pathways in adult neurogenesis of the hippocampus

Disrupted-in-schizophrenia 1 (DISC1) is a multifunctional scaffold protein which plays an important role in neurogenesis and neural development in the adult brain, especially in the dentate gyrus (DG) of the hippocampus. Accumulated research has unveiled the role of DISC1 in several aspects of neural development and neurogenesis, such as neuronal maturation, proliferation, migration, positioning, differentiation, dendritic growth, axonal outgrowth, and synaptic plasticity. Studies on the function of this protein have explored multiple facets, including variants and missense mutants in genetics, proteins interactivity and signaling pathways in molecular biology, and pathogenesis and treatment targets of major mental illness, and more. In this review, we present several signaling pathways discussed in recent research, such as the AKT signaling pathway, GABA signaling pathway, GSK3β signaling pathway, Wnt signaling pathway, and NMDA-R signaling pathway. DISC1 interacts, directly or indirectly, with these signaling pathways and they co-regulate the process of adult neurogenesis in the hippocampus.     

Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019)

Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory processes or cancer and reflects no role in the guarding stomach lining. Thus, selective COX-2 inhibition can significantly reduce the adverse effects including GI tract damage and hepatotoxic effects of traditional NSAIDs like aspirin, ibuprofen, etc. Recent developments on COX-2 inhibitors is primarily focused on improving the selectivity index of the drug towards COX-2 along with enhancing the potency of the drug by modifying the scaffolds of Coxibs currently in the market like Celecoxib, Indomethacin, Oxaprozin, etc. We have reported the progress on new COX-2 inhibitors in the last decade (2008–2019) focussing on five heterocyclic rings- Pyrazole, Indole, Oxazole, Pyridine and Pyrrole. The addition of various moieties to these core rings and their structure-activity relationship along with their molecular modelling data have been explored in the article. This review aims to aid medicinal chemists in the design and discovery of better COX-2 inhibitors constructed on these five heterocyclic pharmacophores.     

Human leukocyte formin: a novel protein expressed in lymphoid malignancies and associated with Akt

The very large family of Formin proteins is involved in processes such as morphogenesis, embryonic differentiation, cell polarity, and cytokinesis. A novel human gene from the Formin family, denominated human leukocyte formin gene, was cloned. The cDNA of the gene was determined to be 3959bp long with an open reading frame of 3302bp and computational analysis located this gene on chromosome 17, suggesting that it is composed of 27 exons. Northern blot analysis revealed a restricted expression of mRNA in the thymus, spleen, and peripheral blood leukocytes in normal human tissues. Western blot analysis demonstrated that the protein encoded by this gene is overexpressed in lymphoid malignancies; cancer cell lines and peripheral blood leukocyte from chronic lymphocytic leukemia (CLL) patients. Furthermore, the human leukocyte formin protein was observed to associate with Akt, a critical survival regulator in many different cell types.     

衰老对小鼠胸腺细胞表面抗原表达的影响

采用流式细胞计技术和胚胎胸腺器官体外培养实验研究不同年龄小鼠胸腺细胞的发育。结果表明,随着小鼠年龄的增长,胸腺细胞的细胞表型由Ｐｇｐ－１高向Ｐｇｐ－１低下调表达受阻;老年组小鼠胸腺与幼年组小鼠胸腺相比,含有较多的ＣＤ４和ＣＤ８双阴性细胞和Ｐｇｐ－１阳性细胞,较少ＣＤ４和ＣＤ８双阳性细胞和ＭＥＬ－１４阳性细胞。     

MicroRNAs in Lymphoma: Regulatory Role and Biomarker Potential

Although it is now evident that microRNAs (miRNAs) play a critical regulatory role in many, if not all, pathological and physiological processes, remarkably they have only formally been recognized for less than fifteen years. These endogenously produced short non-coding RNAs have created a new paradigm of gene control and have utility as both novel biomarkers of cancer and as potential therapeutics. In this review we consider the role of miRNAs in lymphoid biology both under physiological (i.e. lymphopoiesis) and malignant (i.e. lymphomagenesis) conditions. In addition to the functional significance of aberrant miRNA expression in lymphomas we discuss their use as novel biomarkers, both as a in situ tumour biomarker and as a non-invasive surrogate for the tumour by testing miRNAs in the blood of patients. Finally we consider the use of these molecules as potential therapeutic agents for lymphoma (and other cancer) patients and discuss some of the hurdles yet to be overcome in order to translate this potential into clinical practice