ABSTRACT
La psoriasis es una enfermedad dermatológica principalmente inmunitaria que se puede desencadenar por diferentes factores, esta patología es de gran importancia médica ya que compromete la calidad de vida de la persona. La psoriasis es una enfermedad que puede tener dificultad en el enfoque diagnóstico por los casos atípicos de su presentación y puede ser confundida con otras patologías. El estudio de la semiología homeopática tiene su complejidad al traducir lo que el paciente expresa en su propio lenguaje al lenguaje homeopático y más específicamente al lenguaje del Repertorio. Ante esto se necesita un conocimiento claro de los síntomas tanto subjetivos como objetivos de la psoriasis. También surgen dificultades al estudiar aisladamente los síntomas, pues ellos forman parte de una totalidad y la mayoría de las veces se asocian e interrelacionan armónicamente dando una imagen coherente, un perfil definido. En este trabajo se presenta una revisión sistemática de la literatura, de tipo cualitativo, narrativo y documental realizado a partir de la búsqueda de síntomas en el repertorio Syntesis asociados con la psoriasis, así como la revisión de las materias médicas de Boericke, Kent, Lathoud, Vannier y Vijnovsky; haciendo énfasis en la condición clínica en estudio. Finalmente se presenta la repertorizacion de un caso de psoriasis
Subject(s)
Humans , Homeopathic Diagnoses , Homeopathic Semiology , Psoriasis/diagnosis , Homeopathic Repertory , Complementary TherapiesABSTRACT
Doppel, a prion-like protein, is a GPI-membrane anchored protein generally not expressed in the Central Nervous System (CNS) of different mammalian species, including human. Nevertheless, in astrocytomas, a particular kind of glial tumors, the doppel encoding gene (PRND) is over-expressed and the corresponding protein product (Dpl) is ectopically localized in the cytoplasm of the tumor cells. In this study we have analysed the sub-cellular localization of Dpl using double-immunofluorescence staining and confocal microscopy examinations in two astrocytoma-derived human cell lines (IPDDC-A2 and D384-MG). Our results confirmed that Dpl is localized in the cytoplasm of the astrocytoma cells and indicated that it is mostly associated with Lamp-1 and Limp-2 positive lysosomal vesicles and, marginally, to the Golgi apparatus and other cellular organelles. Noticeably, none of the examined tumor cells showed a membrane-Dpl localization. The membrane-associated Dpl expression was restored after the transfection of the astrocytoma cells with mutated Dpl-expression vectors in its glycosylation sites. Additionally, Dpl showed altered expression and traffic using the acidotropic agent ammonium chloride, leading to the accumulation of Dpl in nascent exocytic vesicles. Altogether, these results indicated that in the astrocytic tumor cells Dpl has an altered biosynthetic trafficking, likely derived from abnormal post-translational processes: these modifications do not permit the localization of Dpl in correspondence of the plasma membrane and lead to its intracellular accumulation in the lysosomes. In these proteolytic compartments, the astrocytic tumor cells might provide to the degradation of the excess of a potentially cytotoxic Dpl product.
Subject(s)
Astrocytes/metabolism , Brain Neoplasms/metabolism , Glioblastoma/metabolism , Oligodendroglioma/metabolism , Prions/metabolism , Adult , Ammonium Chloride/pharmacology , Astrocytes/ultrastructure , Brain Neoplasms/pathology , Cell Compartmentation , Cell Culture Techniques , Cell Membrane/metabolism , Cell Membrane/ultrastructure , GPI-Linked Proteins , Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Glycosylation , Glycosylphosphatidylinositols/genetics , Glycosylphosphatidylinositols/metabolism , HeLa Cells , Humans , Lysosomes/metabolism , Lysosomes/ultrastructure , Male , Mutant Proteins/analysis , Mutant Proteins/genetics , Mutant Proteins/metabolism , Oligodendroglioma/pathology , Prions/analysis , Prions/genetics , Protein Transport , Recombinant Proteins/analysis , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , TransfectionABSTRACT
Doppel (Dpl) is a paralogue of the mammalian Prion (PrP) protein. It is abundant in testis and, unlike PrP, it is expressed at low levels in the adult central nervous system (CNS). Besides, Dpl overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In this study the doppel gene (PRND) mRNA and protein expression in PRT-HU2 and IPDDC-A2 astrocytoma-derived cell lines was investigated. Northern blot analysis revealed two equally abundant PRND mRNA isoforms, while real-time PCR, on nuclear and cytoplasmic RNA fractions, and cRNA in situ hybridization, on astrocytoma cells and bioptical specimens, showed a nuclear retention of PRND transcripts. Western blot analysis showed that the amount of protein expressed is low compared to the level of mRNA. Moreover deglycosylation studies indicated that Dpl undergoes unusual glycosylation processes. Immunohistochemistry experiments demonstrated that Dpl was mainly localised in the cytoplasm of the astrocytic tumor cells, and that it failed to be GPI-anchored to the cell membrane. This unusual cellular localization was also confirmed through EGFP-Dpl expression in astrocytomas; on the contrary, HeLa cells exhibited the expected Dpl membrane localization. Our findings suggest an aberrant doppel gene expression pattern, characterized by a substantial nuclear retention of the transcript, an altered post-translational modification of the protein and an unusual cytoplasmic localization.
Subject(s)
Astrocytoma/metabolism , Brain Neoplasms/metabolism , Cell Nucleus/metabolism , Prions/biosynthesis , RNA, Messenger/metabolism , Astrocytoma/genetics , Blotting, Northern , Blotting, Western , Brain Neoplasms/genetics , Cell Line, Tumor , Cytoplasm/metabolism , GPI-Linked Proteins , Gene Expression , Gene Expression Profiling , Humans , Immunohistochemistry , Protein Biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Transcription, Genetic , TransfectionABSTRACT
The cellular prion protein (PrP(C)) is a highly conserved protein throughout the evolution of mammals and therefore is thought to play important cellular functions. Despite decades of intensive researches, the physiological function of PrP(C) remains enigmatic. Differently, in particular pathological contexts, generally referred as transmissible spongiform encephalopathies, a conformational isoform of PrP(C), i.e., PrP(Sc), is considered the causative agent of these diseases. In this study, we investigated putative PrP(C) cellular functions through the identification of PrP(C) protein interactants. Using a bacterial two-hybrid approach, we identified a novel interaction between PrP(C) and a two-pore potassium channel protein, TREK-1. This interaction was further verified in transfected eukaryotic cells using co-immunoprecipitation and confocal microscopic analysis of the fluorescent transfected proteins. Importantly, in the cerebellar cortex, the endogenous PrP(C) and TREK-1 proteins exhibited co-localization signals in correspondence of the Purkinje cells. Furthermore, a deletion mapping study defined the carboxyl-terminal regions of the two proteins as the possible determinants of the PrP(C)-TREK-1 interaction. Our results indicated a novel PrP(C) interacting protein and suggested that this complex might be relevant in modulating a variety of electrophysiological-dependent cellular responses.
