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  • Articles  (6)
  • Blackwell Science Ltd  (3)
  • Munksgaard International Publishers  (3)
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  • Articles  (6)
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  • 1
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: APAF-1 plays a pivotal role in mitochondria-dependent apoptosis, binding to cytochrome c and favoring activation of caspase-9. It has been shown that epigenetic silencing of the APAF-1 gene is a common event in several metastatic melanoma cells in vitro. We determined, by Western blot, variation in the level of expression of APAF-1 in several human melanoma cell lines and, by immunohistochemistry, in a group of 106 histological samples including benign and malignant melanocytic lesions. We observed APAF-1 down-regulation or loss of expression in two metastatic melanoma cell lines, compared to primary melanoma cell lines. The immunohistochemical analysis revealed a significant difference in APAF-1 staining between nevi and melanomas. In addition, we found a significant negative correlation between APAF-1 expression level and tumor thickness and between primary melanomas and metastases. We conclude that loss of APAF-1 expression can be considered as an indicator of malignant transformation in melanoma.
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In order to identify genes relevant for melanoma development, we carried out cDNA array experiments employing an in vitro model of human melanoma progression, consisting of two cell lines: one, LP, derived from a primary melanoma and the other, LM, from its metastatic supraclavicular lymph node. Basic cDNA array data identified 26 genes as down-regulated in the LM cell line. Northern blot analysis confirmed an effective transcriptional down-regulation for five out of 13 genes analyzed. The products of these five genes belong to different functional protein types, such as transcription and translation regulators (Edg-2, eIF-3 p110, and RNPL/RBM3), extracellular communicators (PRSS11) and members of the major histocompatibility complex (β2-microglobulin). Some previously described differences in expression patterns, such as loss of HLA I, were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of several genes during melanoma progression. In particular, reduced Edg-2 gene product expression was also confirmed in a group of 50 primary melanomas and unrelated metastases. In conclusion, comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been known for a long time that subcortical input drives the specification of cortical areas. Molecular signals mediating this instructive effect from the periphery are poorly understood. In foetal or neonatal rats, ablation of whisker follicles, transection of the infraorbital nerve, inhibition of axonal transport, but not impulse activity blockade, prevent formation of barrels in the primary somatosensory cortex (S1). These findings suggest that a chemical signal, possibly arising from the skin or the follicle, may be responsible for somatotopic pattern formation in S1. Neurotrophins promote survival and differentiation of primary sensory neurons, and are expressed in the whisker pad during development. Neonatal rats received gelfoam impregnated with NGF, BDNF or NT-3 under the whisker pad following surgical denervation of whisker rows D and E on P0. Barrel formation in S1 was assessed on P7 by acetylcholinesterase histochemistry and 5-HT-immunohistochemistry. BDNF and NT-3, but not NGF, promoted development of the cortical barrels corresponding to denervated whiskers. Furthermore, BDNF and NT-3 prevented the lesion-induced expansion of row C barrels, while NGF appeared to promote row C expansion. Our results suggest that BDNF and NT-3 arising from the whisker pad are involved in the formation and/or maintenance of the barrel pattern in S1. These findings are potentially relevant for the prevention of sensory disturbances possibly due to reorganization of central sensory circuits after peripheral nerve lesions in humans.
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study shows that unilateral transection of the infraorbital nerve (ION) in newborn (P0) rats induces apoptosis in the contralateral ventrobasal thalamic (VB) complex, as evidenced by terminal transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) and electron miscroscopy. Double-labelling experiments using retrograde transport of labelled microspheres injected into the barrel cortex, followed by TUNEL staining, show that TUNEL-positive cells are thalamocortical neurons. The number of TUNEL-positive cells had begun to increase by 24 h postlesion, increased further 48 h after nerve section, and decreased to control levels after 120 h. Lesion-induced apoptosis in the VB complex is less pronounced if ION section is performed at P4, and disappears if the lesion is performed at P7. This time course closely matches the critical period of lesion-induced plasticity in the barrel cortex. Nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), applied on the ION stump alone or in combination, are able to partially rescue thalamic neurons from apoptosis. Total cell counts in the VB complex of P7 animals that underwent ION section at P0 confirm the rescuing effect of BDNF and NGF. Blockade of axonal transport in the ION mimics the effect of ION section. These data suggest that survival-promoting signals from the periphery, maybe neurotrophins, are required for the survival of higher-order neurons in the somatosensory system during the period of fine-tuning of neuronal connections. We also propose that anterograde transneuronal degeneration in the neonatal rat trigeminal system may represent a new animal model for studying the pathways of programmed cell death in vivo.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 42 (2003), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A 24-year-old woman was seen in consultation for a painless tumor of 6 cm in diameter of the vulva. The excised oval tumor was situated in the lower part of the dermis and encapsulated (〈link href="#f1"〉Fig. 1A). It was completely composed of multiple adjacent cell complexes, each containing 5–20 laminar cells and resembling Wagner–Meissner touch corpuscles (〈link href="#f1"〉Fig 1B and 1C). The nuclei of the laminar cells were located at the periphery of the corpuscles or were arranged transversely to the long axis of these structures along the lamellae. The nuclei were oval or showed one or several nuclear invaginations. Mitoses were not observed. These corpuscles showed a positive immunohistochemical reaction for S-100 (〈link href="#f1"〉Fig. 1D), vimentin, and neuron-specific endase (NSE) (not shown), but were negative for CD-68, desmin, and α-actin. The gross and microscopic morphology and the immunohistochemical findings were compatible with a diagnosis of Wagner–Meissner neurilemmoma of the vulva. The patient remained disease free for 2 years after surgery.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD1756_1:IJD_1756_f1"/〉(A) Gross appearance of the excised oval tumor of the vulva, situated in the lower part of the dermis and encapsulated. (B) Histologic examination of the excised lesion revealed a monomorphous morphology with typical touch corpuscles with lamellar structures (hematoxylin and eosin; original magnification, × 50). (C) Higher magnification of (B). The nuclei are predominantly located at the periphery of the corpuscles (hematoxylin and eosin; original magnification, × 250). (D) The tactile corpuscles show a positive reaction for protein S-100 (3-amino-9-ethylcarbazide, × 250)
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Apoptosis protease-activating factor-1 (Apaf-1) is a key regulator of the mitochondrial apoptotic pathway, being the central element of the multimeric apoptosome formed by procaspase 9, cytochrome c, and Apaf-1 itself. In this review, the principal aspects about Apaf-1 gene structure and function, and its role in the apoptotic machinery, are described. Moreover, the most recent findings about the involvement of this molecule in melanoma progression and chemoresistance, as well as the clinico-pathological relevance of these findings in the treatment of this deadly disease, are reported.
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