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Cytoplasmic Granules (cytoplasmic + granule)
Selected AbstractsSecretory activity in medullary thyroid carcinoma: A cytomorphological and immunocytochemical studyDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2007D.Sc., Dilip K. Das M.B.B.S., F.R.C.Path., Ph.D. Abstract Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level. Diagn. Cytopathol. 2007;35:329,337. © 2007 Wiley-Liss, Inc. [source] Cytology of the central zone of the prostateDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2003Lars Egevad M.D., Ph.D. Abstract The prostate has three anatomical regions: the peripheral, transition, and central zones (CZ). The CZ has distinct histological features, but its cytological morphology has not been described. This study was done on surgical specimens to ensure that samples were representative of the CZ, and that no prostatic intraepithelial neoplasia (PIN) or cancer contaminated the smears. An incision was made in the CZ of 51 prostatectomy specimens, and cells were scraped from cut surfaces. After exclusion of samples contaminated by PIN or cancer or with poor cell yield, 39 Giemsa-stained smears remained for analysis. Large branching epithelial sheets with geographic architecture and crowded nuclei were seen in 97% of smears. Epithelial clusters with elongated palisaded nuclei were identified in 80% of cases, but were always a minor component. Visible nucleoli (97%), cytoplasmic vacuoles (97%), and smooth muscle cells in the background (95%) were common. Blue-green cytoplasmic granules resembling seminal vesicle pigment were seen in 97%. Magenta-colored cytoplasmic pigment, similar to granules seen in other regions of the prostate, was found in 74%. Recognition of CZ epithelium as a benign constituent of prostate cytology is important because elongated cells, crowded nuclei, and visible nucleoli may otherwise be misinterpreted as PIN or cancer. Diagn. Cytopathol. 2003;28:239,244. © 2003 Wiley-Liss, Inc. [source] Altered subcellular location of phosphorylated Smads in Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2006Uwe Ueberham Abstract A number of growth factors and cytokines, such as transforming growth factor beta 1 (TGF-,1), is elevated in Alzheimer's disease (AD), giving rise to activated intracellular mitogenic signaling cascades. Activated mitogenic signaling involving the mitogen-activated protein kinases (MAPKs) and other protein kinases might alter the phosphorylation states of structural proteins such as tau, resulting in hyperphosphorylated deposits. Many intracellular signaling proteins are potential targets of misregulated phosphorylation and dephosphorylation. Recently, a crosstalk between MAPKs and Smad proteins, both involved in mediating TGF-,1 signaling, has been reported. Although TGF-,1 has previously been shown to be involved in the pathogenesis of AD, the role of Smad proteins has not been investigated. In this study we thus analysed the subcellular distribution of phosphorylated Smad2 and Smad3 in the hippocampus of both normal and AD brains. Here we report on strong nuclear detection of phosphorylated Smad2 and Smad3 in neurons of control brains. In AD brains these phosphorylated proteins were additionally found in cytoplasmic granules in hippocampal neurons, within amyloid plaques and attached to neurofibrillary tangles. Our data suggest a critical role of Smad proteins in the pathogenesis of AD. [source] The 21st century renaissance of the basophil?EXPERIMENTAL DERMATOLOGY, Issue 11 2006Current insights into its role in allergic responses, innate immunity Abstract:, Basophils and mast cells express all the three subchains of the high-affinity immunoglobulin E (IgE) receptor Fc,RI and contain preformed histamine in the cytoplasmic granules. However, it is increasingly clear that these cells play distinct roles in allergic inflammatory disease. Despite their presence throughout much of the animal kingdom, the physiological function of basophils remains obscure. As rodent mast cells are more numerous than basophils, and generate an assortment of inflammatory cytokines, basophils have often been regarded as minor players in allergic inflammation. In humans, however, basophils are the prime early producers of interleukin (IL)-4 and IL-13, T helper (Th)2-type cytokines crucial for initiating and maintaining allergic responses. Basophils also express CD40 ligand which, in combination with IL-4 and IL-13, facilitates IgE class switching in B cells. They are the main cellular source for early IL-4 production, which is vital for the development of Th2 responses. The localization of basophils in various tissues affected by allergic inflammation has now been clearly demonstrated by using specific staining techniques and the new research is shedding light on their selective recruitment to the tissues. Finally, recent studies have shown that basophil activation is not restricted to antigen-specific IgE crosslinking, but can be caused in non-sensitized individuals by a growing list of parasitic antigens, lectins and viral superantigens, binding to non-specific IgE antibodies. This, together with novel IgE-independent routes of activation, imparts important new insights into the potential role of basophils in both adaptive and innate immunity. [source] Mast cells in the amphibian brain during developmentJOURNAL OF ANATOMY, Issue 3 2010Claudia Pinelli Abstract This is the first descriptive study of ontogenesis and anatomical distribution of mast cells in the developing brain of three different amphibian species. In the toad and the green frog, mast cells are preferentially located in: (i) the meningeal lining (pia mater), (ii) the choroid plexuses, both anterior and posterior, and (iii) the neuropil, in close association with the epithelial cell lining of blood vessels. It is only in the perennially aquatic African clawed frog that mast cells never appear inside brain ventricles and within the neuropil. Mast cells first become identifiable in brain of different species in different stages of development. While there are differences in the number of mast cells in different species at different stages of development, the number nearly doubles in all three species during the transition from pro-metamorphic stage of larval development to the peak of metamorphic climax. Furthermore, the number of mast cells is comparatively higher in the toad and remarkably lower in the fully aquatic Xenopus laevis, in which species the first appearance of identifiable mast cells during larval development occurs much later than in equivalent stages of development of the toad and the green frog. The secretory nature of mast cells can be assumed by the presence of cytoplasmic granules, which may show species-specific texture. Further experimental analyses are required to unveil the usefulness of mast cells in the amphibian brain. [source] Exposure to cadmium-contaminated soils increases allergenicity of Poa annua L. pollenALLERGY, Issue 10 2010R. Aina To cite this article: Aina R, Asero R, Ghiani A, Marconi G, Albertini E, Citterio S. Exposure to cadmium-contaminated soils increases allergenicity of Poa annua L. pollen. Allergy 2010; 65: 1313,1321. Abstract Background:, Pollution is considered as one main cause for the increase of allergic diseases. Air pollutants may cause and worsen airway diseases and are probably able to make pollen allergens more aggressive. Previous studies looked at traffic-related air pollution, but no data about the effects of polluted soils on pollen allergens are available. We aimed to assess the effects of plant exposure to cadmium-contaminated soil on allergenicity of the annual blue grass, Poa annua L, pollen. Methods:,Poa plants were grown in soil contaminated or not contaminated (control) with cadmium. At flowering, mature pollen was analyzed by microscopy, to calculate the percentage of pollen grains releasing cytoplasmic granules, and by proteomic techniques to analyze allergen proteins. Allergens were identified by sera from grass pollen,allergic patients and by mass spectrometry. Results:, Pollen from Cd-exposed plants released a higher amount of allergenic proteins than control plants. Moreover, Cd-exposed pollen released allergens-containing cytoplasmic grains much more promptly than control pollen. Group 1 and 5 allergens, the major grass pollen allergens, were detected both in control and Cd-exposed extracts. These were the only allergens reacting with patient's sera in control pollen, whereas additional proteins strengthening the signal in the gel region reacting with patient's sera were present in Cd-exposed pollen. These included a pectinesterase, a lipase, a nuclease, and a secretory peroxydase. Moreover, a PR3 class I chitinase-like protein was also immunodetected in exposed plants. Conclusion:, Pollen content of plants grown in Cd-contaminated soils is more easily released in the environment and also shows an increased propensity to bind specific IgE. [source] Ancient Weapons for Attack and Defense: the Pore-forming Polypeptides of Pathogenic Enteric and Free-living Amoeboid Protozoa,THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2004MATTHIAS LEIPPE ABSTRACT Pore-forming polypeptides have been purified from several amoeboid protozoans that are well-known human pathogens. Obligate enteric parasites, such as Entamoeba histolytica, and free-living but potentially highly pathogenic species, such as Naegleria fowleri, contain these cytolytic molecules inside cytoplasmic granules. Comprehensive functional and structural studies have been conducted that include isolation of the proteins from their natural sources, monitoring of their biological activity towards different targets, and molecular cloning of the genes of their precursors. In the case of the most prominent member of the protein family, with respect to protozoans, the three-dimensional structure of amoebapore A was solved recently. The amoebic pore-forming polypeptides can rapidly perforate human cells. The antibacterial activity of amoebapores and of related polypetides from free-living protozoa points to a more vital function of these molecules: inside the digestive vacuoles they combat growth of phagocytosed bacteria which are killed when their cytoplasmic membranes are permeabilized. The concommitant activity of these proteins towards host cells may be due to a coincidental selection for an efficient effector molecule. Nonetheless, several lines of evidence indicate that these factors are involved in pathogenesis of fatal diseases induced by amoeboid protozoa. [source] Regional Analysis of the Ependyma of the Third Ventricle of Rat by Light and Electron MicroscopyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2008T. C. Mathew Summary Ependymal lining of cerebral ventricles lies at the interface between the ventricular cavities and the brain parenchyma. Ependymal cells are involved in various functions within the brain and play a major role in the production of the chemical principals of the cerebrospinal fluid. Histological studies on the regional variation of the third ventricular ependyma and the subependyma of adult rats were carried out by light and electron microscopic methods. For light microscopic analysis, methacrylate sections were used. In addition to the routine haematoxylin and eosin (H and E) staining for histological studies, the sections were stained with toluidine blue, cresyl violet and periodic acid Schiff's reagent (PAS). A regional analysis of the ependyma of the third ventricle showed that in most regions the ependyma was monolayered. The sidewalls and floor of the ventral portion of the third ventricle showed a multilayered ependyma. For descriptive purposes at the light microscopic level, the ependymal cells were classified, based on the cell shape (flat, cuboidal or columnar), presence or absence of cilia and the number of cytoplasmic granules present in the cells. Studies of transmission electron microscope have shown that these granules represent the cell organelles of the ependyma. The subependyma also showed a regional morphological variation, and, in most instances, contained glial and neuronal elements. In regions of specific brain nuclei, neurons were the major cell type of the subependyma. PAS staining did not show any positive granules in the ependymal cytosol. Characteristic supraependymal elements were present at the ependymal surface of the third ventricle. [source] Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid,ANNALS OF NEUROLOGY, Issue 6 2009Gregory P. Owens PhD Objective Intrathecal IgG synthesis, persistence of bands of oligoclonal IgG, and memory B-cell clonal expansion are well-characterized features of the humoral response in multiple sclerosis (MS). Nevertheless, the target antigen of this response remains enigmatic. Methods We produced 53 different human IgG1 monoclonal recombinant antibodies (rAbs) by coexpressing paired heavy- and light-chain variable region sequences of 51 plasma cell clones and 2 B-lymphocyte clones from MS cerebrospinal fluid in human tissue culture cells. Chimeric control rAbs were generated from anti-myelin hybridomas in which murine variable region sequences were fused to human constant region sequences. Purified rAbs were exhaustively assayed for reactivity against myelin basic protein, proteolipid protein, and myelin oligodendrocyte glycoprotein by immunostaining of transfected cells expressing individual myelin proteins, by protein immunoblotting, and by immunostaining of human brain tissue sections. Results Whereas humanized control rAbs derived from anti-myelin hybridomas and anti-myelin monoclonal antibodies readily detected myelin antigens in multiple immunoassays, none of the rAbs derived from MS cerebrospinal fluid displayed immunoreactivity to the three myelin antigens tested. Immunocytochemical analysis of tissue sections from MS and control brain demonstrated only weak staining with a few rAbs against nuclei or cytoplasmic granules in neurons, glia, and inflammatory cells. Interpretation The oligoclonal B-cell response in MS cerebrospinal fluid is not targeted to the well-characterized myelin antigens myelin basic protein, proteolipid protein, or myelin oligodendrocyte glycoprotein. Ann Neurol 2009;65:639,649 [source] Role of dystrophins and utrophins in platelet adhesion processBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006Doris Cerecedo Summary Platelets are crucial at the site of vascular injury, adhering to the sub-endothelial matrix through receptors on their surface, leading to cell activation and aggregation to form a haemostatic plug. Platelets display focal adhesions as well as stress fibres to contract and facilitate expulsion of growth and pro-coagulant factors contained in the granules and to constrict the clot. The interaction of F-actin with different actin-binding proteins determines the properties and composition of the focal adhesions. Recently, we demonstrated the presence of dystrophin-associated protein complex corresponding to short dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and Up71), which promote shape change, adhesion, aggregation, and granule centralisation. To elucidate participation of both complexes during the platelet adhesion process, their potential association with integrin , -1 fraction and the focal adhesion system (, -actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays. It was shown that the short dystrophin-associated protein complex participated in stress fibre assembly and in centralisation of cytoplasmic granules, while the utrophin-associated protein complex assembled and regulated focal adhesions. The simultaneous presence of dystrophin and utrophin complexes indicates complementary structural and signalling mechanisms to the actin network, improving the platelet haemostatic role. [source] New indolicidin analogues with potent antibacterial activity,CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2004T.S. Ryge Abstract:, Indolicidin is a 13-residue antimicrobial peptide amide, ILPWKWPWWPWRR-NH2, isolated from the cytoplasmic granules of bovine neutrophils. Indolicidin is active against a wide range of microorganisms and has also been shown to be haemolytic and cytotoxic towards erythrocytes and human T lymphocytes. The aim of the present paper is two-fold. First, we examine the importance of tryptophan in the antibacterial activity of indolicidin. We prepared five peptide analogues with the format ILPXKXPXXPXRR-NH2 in which Trp-residues 4,6,8,9,11 were replaced in all positions with X = a single non-natural building block; N -substituted glycine residue or nonproteinogenic amino acid. The analogues were tested for antibacterial activity against both Staphylococcus aureus American type culture collection (ATCC) 25923 and Escherichia coli ATCC 25922. We found that tryptophan is not essential in the antibacterial activity of indolicidin, and even more active analogues were obtained by replacing tryptophan with non-natural aromatic amino acids. Using this knowledge, we then investigated a new principle for improving the antibacterial activity of small peptides. Our approach involves changing the hydrophobicity of the peptide by modifying the N-terminus with a hydrophobic non-natural building block. We prepared 22 analogues of indolicidin and [Phe4,6,8,9,11] indolicidin, 11 of each, carrying a hydrophobic non-natural building block attached to the N-terminus. Several active antibacterial analogues were identified. Finally, the cytotoxicity of the analogues against sheep erythrocytes was assessed in a haemolytic activity assay. The results presented here suggest that modified analogues of antibacterial peptides, containing non-natural building blocks, are promising lead structures for developing future therapeutics. 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