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  • 1
    Publication Date: 2018-09-28
    Description: Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term outcomes with standard therapy. To better understand this group of tumors, we evaluated their molecular signature using gene expression profiling. DUSP22- rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of genes associated with JAK-STAT3 signaling, a pathway contributing to growth in the majority of ALCLs. Reverse-phase protein array and immunohistochemical studies confirmed the lack of activated STAT3 in DUSP22- rearranged ALCLs. DUSP22- rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes and showed marked DNA hypomethylation by reduced representation bisulfate sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL cells recapitulated the overexpression of CTAs and other DUSP22 signature genes. In addition, DUSP22- rearranged ALCLs minimally expressed PD-L1 compared with other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA class II. Taken together, these findings indicate that DUSP22 rearrangements define a molecularly distinct subgroup of ALCLs, and that immunogenic cues related to antigenicity, costimulatory molecule expression, and inactivity of the PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like immunogenic molecular signature through the use of demethylating agents and/or immune checkpoint inhibitors.
    Keywords: Immunobiology and Immunotherapy, Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2018-10-05
    Description: The haploid genome of the pathogenic fungus Zymoseptoria tritici is contained on "core" and "accessory" chromosomes. While 13 core chromosomes are found in all strains, as many as eight accessory chromosomes show presence/absence variation and rearrangements among field isolates. The factors influencing these presence/absence polymorphisms are so far unknown. We investigated chromosome stability using experimental evolution, karyotyping, and genome sequencing. We report extremely high and variable rates of accessory chromosome loss during mitotic propagation in vitro and in planta . Spontaneous chromosome loss was observed in 2 to 〉50% of cells during 4 weeks of incubation. Similar rates of chromosome loss in the closely related Zymoseptoria ardabiliae suggest that this extreme chromosome dynamic is a conserved phenomenon in the genus. Elevating the incubation temperature greatly increases instability of accessory and even core chromosomes, causing severe rearrangements involving telomere fusion and chromosome breakage. Chromosome losses do not affect the fitness of Zymoseptoria tritici in vitro , but some lead to increased virulence, suggesting an adaptive role of this extraordinary chromosome instability.
    Print ISSN: 0016-6731
    Topics: Biology
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 158 (1975), S. 451-459 
    ISSN: 1432-0878
    Keywords: Pineal nerve ; Sheep and rabbit fetuses ; Subcommissuralorgan ; Ontogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The presence of a nerve located just caudal to the pineal gland in the mid-sagittal plane is demonstrated in sheep and rabbit fetuses. This nerve lies freely in the subarachnoid space and extends from the pineal gland to a region of the CNS located dorsal to the rostralmost part of the subcommissural organ (SCO). In rabbit fetuses the nerve is observed on days 23 and 24 of gestation; we suggest that it is an ontogenetic equivalent to the pineal nerve of anuran amphibians. The developmental fate of the mammalian fetal pineal nerve is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0878
    Keywords: Pineal gland ; Monkey (Cercopithecus aethiops) ; Cat ; Central innervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Silver-impregnated series of cat and monkey (Cercopithecus aethiops) brains were studied in an attempt to demonstrate the existence of nervous connections between the brain and the pineal gland via the pineal stalk (central pineal connections). The presence of such connections between both the pineal gland and the habenular area, and between the pineal gland and the posterior commissure was verified in this study. A well defined median nerve tract between the pineal gland and the posterior commissure is described.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 230 (1983), S. 259-272 
    ISSN: 1432-0878
    Keywords: Pineal organ, Mongolian gerbil ; Pinealopetal innervation ; Degeneration, synapses ; Habenular lesions ; Acetylcholinesterase-positive neurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Nerve fibers connecting the brain with the pineal gland of the Mongolian gerbil (central pinealopetal fibers) were investigated by means of light and electron microscopy. Several myelinated fibers penetrate from the brain into the deep pineal gland, extend further into the pineal stalk and continue to the superficial portion of the pineal gland. In the centripetal direction these fibers were traced to the stria medullaris and to the habenular nuclei, where they turned laterad and then occupied a position immediately ventral to the optic tract. As shown in electron micrographs, lesions of the habenular area led to degeneration of myelinated fibers and nerve boutons in the deep pineal gland, the pineal stalk and the superficial pineal gland. Only boutons containing clear transmitter vesicles (devoid of a dense core) were observed to degenerate after the habenular lesions. On the other hand, removal of the superior cervical ganglia resulted in degeneration of boutons containing small (40 to 60 nm in diameter) dense-core vesicles. Several of the nerve fibers that penetrate into the deep pineal directly from the brain (central fibers) exhibited a positive reaction for acetylcholinesterase (AChE). AChE-positive perikarya were located in the projections of the stria medullaris, the lateral portions of the deep pineal, the area of the posterior commissure, and the periventricular gray of the mesencephalon. Such perikarya were found neither in the pineal stalk nor in the superficial pineal gland. These results present anatomical evidence that the pineal organ of the Mongolian gerbil receives multiple nervous inputs mediated by peripheral autonomic (i.e., sympathetic) nerve fibers, on the one hand, and by central fibers, on the other.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0878
    Keywords: Pineal gland ; Serotonin ; Immunohistochemistry ; Third ventricle ; Golden hamster, Mesocricetus auratus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Serotonin-like immunoreactivity was investigated in the pineal complex of the golden hamster by use of the indirect immunohistochemical technique. The superficial and deep portions of the pineal gland, and also the pineal stalk exhibited an intense cellular immunoreaction for serotonin. In addition, perivascular serotonin-immunoreactive nerve fibers were observed. Some serotonin-immunoreactive processes of the pinealocytes terminated on the surface of the ventricular lumen in the pineal and suprapineal recesses, indicating a receptive or secretory function of these cells. Several serotonin-immunoreactive processes connected the deep pineal with the habenular area. One week after bilateral removal of both superior cervical ganglia the serotonin immunoreaction of the entire pineal complex was greatly decreased. However, some cells in the pineal complex, of which several exhibited a neuron-like morphology, remained intensively stained after ganglionectomy. This indicates that the indoleamine content of some cells in the pineal complex of the golden hamster is independent of the sympathetic innervation.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Key words Calcitonin gene-related peptide ; Vasoactive intestinal peptide ; Neuropeptide Y ; Colocalization ; Trigeminal ganglion ; Rat (Wistar)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Pituitary adenylate cyclase-activating polypeptide (PACAP)-immunoreactive nerve fibres were demonstrated in the rat pineal gland. These fibres entered the pineal gland through the conarian nerve at the distal tip of the gland. A high density of the fibres was observed in the capsule of the gland, from where the immunoreactive elements penetrated into the pineal perivascular spaces and parenchyma. The majority of PACAP-immunoreactive nerve fibres also contained calcitonin gene-related peptide (CGRP). Some PACAP-immunoreactive nerve fibres contained neuropeptide Y (NPY), but only occasionally was PACAP colocalized with vasoactive intestinal peptide (VIP). After removal of both superior cervical ganglia, a high number of PACAP-containing nerve fibres were still present in the gland. In the nervous system PACAP is present in two isoforms, PACAP-38 and PACAP-27. The concentration of PACAP-38 in the superficial pineal gland was determined by radioimmunoassay to be 20.4 pmol/g tissue at midday and 18.9 pmol/g tissue at midnight. The concentration of PACAP-27 was only about 3% of the concentration of PACAP-38. In summary, this study is the first demonstration of a PACAP-containing innervation of the rat pineal gland. The PACAP concentration in the pineal gland does not exhibit a day-night difference. The colocalization of PACAP with calcitonin gene-related peptide in the pinealopetal nerve fibres indicates that the majority of PACAP-immunoreactive nerve fibres might originate from the trigeminal ganglion.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0878
    Keywords: Pineal gland ; Leu-enkephalin ; Met-enkephalin ; Synaptic contacts ; Paracrine regulation ; European hamster, Cricetus cricetus (Rodentia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract By use of antibodies raised against leu-enkephalin and met-enkephalin immunoreactive, opioidergic bi- and multipolar cells were demonstrated in the pineal gland of the European hamster. Ultrastructural analysis of these opioidergic cells revealed them to be pinealocytes. Processes emerged from the cell bodies and terminated in club-shaped swellings containing many small clear and some larger granular vesicles. Some of the terminals made synapse-like contacts with non-immunoreactive pinealocytes. The presence of the opioidergic pinealocytes strongly indicates that the pineal gland of the European hamster, in addition to its pinealopetal nervous regulation, is regulated by intrapineal peptidergic pinealocytes via a synaptic mechanism. A possible paracrine role of the opioidergic cells must also be considered.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0878
    Keywords: Key words Pineal ; Vasotocin ; Vasopressin ; In situ hybridization ; Neurons ; Bovine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Arginine vasopressin (AVP) is the main antidiuretic hormone in mammals and arginine vasotocin (AVT) in submammalian vertebrates. The possibility that the genetic material encoding AVT is maintained in mammals is controversial. In this study, we investigated by radioactive in situ hybridization the possible presence of the mRNA encoding AVP and AVT, and using immunocytochemistry the presence of structures immunoreactive for AVP and AVT in the bovine pineal gland. In situ hybridization was performed by use of 35S-labelled oligoprobes. Immunocytochemistry was performed using specific polyclonal rabbit antibodies and the avidin-biotin-complex method. In situ hybridization revealed positive signals for both AVP mRNA and AVT mRNA in a few cells scattered throughout the pineal body. Immunocytochemistry revealed thin AVP-immunoreactive fibres in the pineal stalk and the pineal gland. It also revealed staining of several AVT-immunoreactive nerve fibres in both the pineal stalk and the gland. In addition, polyhedral, neuron-like cell bodies from which two to three processes emerged were also AVT-immunoreactive. Thus, our investigation shows the presence of AVP/AVT-immunoreactive cellular structures in the bovine pineal gland. Our data further show the presence of mRNAs encoding both AVT and AVP. We therefore suggest that AVT mRNA is translated into an AVT-like peptide in the bovine pineal.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0942-0940
    Keywords: Peripheral nerve ; Neurilemmoma ; Haemangioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five cases of a peripheral nerve tumour with both neurilemmoma and haemangioma components are reported. Three tumours were intraspinal, one tumour originated in the acoustic nerve, and one was in the brachial plexus. Because of rapid progression these mixed tumours should be considered in the differential diagnosis of intraspinal malignancies.
    Type of Medium: Electronic Resource
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