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Pathogenetic Pathway (pathogenetic + pathway)
Selected AbstractsConfluent and reticulated papillomatosis and acanthosis nigricans in an obese girl: two distinct pathologies with a common pathogenetic pathway or a unique entity dependent on insulin resistance?JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2006SP Cannavň [source] 1334: Autofluorescence: new tool to follow dry eye AMD?ACTA OPHTHALMOLOGICA, Issue 2010MN MENKE Purpose In the pathophysiolgy of dry (atrophic) age related macular degeneration (AMD) aging of the retinal pigment epithelium (RPE) plays a key role. Accumulation of lipofuscin granules in the RPE cells represents a common downstream pathogenetic pathway in AMD. Lipofuscin is derived from chemically modified residues of incompletely digested photoreceptor outer segment discs. Detection of lipofuscin in vivo is possible by using fundus autofluorescence (FAF) imaging. The clinical application and possible implications of autofluorescence imaging in dry AMD will be discussed. Methods When stimulated with light in the blue to green range, lipofuscin granules emit a characteristic yellow fluorescence. FAF imaging using a scanning laser ophthalmoscope allows visualization of the topographic distribution of lipofuscin over large retinal areas. Examples of FAF images will be presented to demonstrate various FAF patterns and to discuss the clinical significance of these findings. Results In areas of geographic atrophy FAF images show very low autofluorescence intensity. This is due to the loss of RPE cells including the lipofuscin granules. In the junctional zone between atrophic and normal retina, levels of increased autofluorescence intensity may occur due to excessive accumulation of lipofuscin in the RPE cells. Longitudinal observations further suggest that the extension of the total area with increased autofluorescence intensity surrounding atrophy at baseline has a strong positive correlation with atrophy progression rate over time. Conclusion FAF imaging is an important diagnostic tool to follow the progression of dry AMD and other degenerative macular diseases and should always be considered in cases were the status of the RPE is unknown. [source] New perspectives in retinal imaging: fundus autofluorescence and age-related macular degenerationACTA OPHTHALMOLOGICA, Issue 2007F HOLZ Fundus Autofluorescence (FAF) imaging using confocal scanning laser ophthalmoscopy is a non-invasive method to to accurately record the topographic distribution of RPE lipofuscin in the human eye in vivo. Excessive lipofuscin accumkulation in the RPE is a common downstream pathogenetic pathway in various complex and monogenetic retinal diseases. Toxic compounds and molecular mechanisms of interference with normal cellular functions have been identified including the dominant fluorophore A2-E. Alterations in fundus autofluorescence (FAF) appearance in eyes with early and late age-related macular degeneration (AMD) can be striking. FAF patterns and distribution do not necessarily correlate with the features of interest in color or angiographic images of eyes with early or late AMD. In the prospective, multicenter FAM study distinct patterns of abnormal FAF were identified and classified in the junctional zone of geographic atrophy (GA). Areas of increased FAF outside GA were associated with variable degrees of loss of retinal sensitivity when tested with microperimetry which suggests a functional correlate of lipofuscin accumulation. Increased FAF preceded the development and enlargement of outer retinal atrophy associated with spread of absolute scotoma in eyes with AMD. Longitudinal examinations showed that the abnormal phenotypic FAF patterns serve as novel prognostic determinants which allows to distinguish fast vs. slow progressors. These findings are relevant and now used to design and carry out interventional trials with agents aimed at slowing down spread of atrophy, e.g. using visual cycle modulators to influence lipofuscinogenesis. Hereby FAF imaging also serves as a mean to accurately delineate and measure areas of GA over time in an automated fashion. A phenotype-genotype correlation was identified for a distinct FAF phenotype subset which was found to represent late-onset Stargardt macular dystrophy mimicking late-stage atrophic AMD. New imaging technologies were recently applied including simultaneous recordings of FAF images and high-resolution, spectral-domain optical coherence tomography (OCT) which allows to identify morphological correlates of abnormal FAF signals in optical biopsies. [source] A clinical perspective of rheumatoid arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2009Hans Ulrich Scherer Abstract In recent years, factors potentially involved in pathogenesis of rheumatoid arthritis have mostly been identified by studying well-defined patient cohorts. Characterization of antibodies from sera of affected patients, family-based heritability studies, genome-wide association scans, the analysis of environmental factors and data from clinical trials have contributed largely to a thorough reassembly of our perception of rheumatoid arthritis. Modified animal models are now crucial to obtain experimental evidence for suggested pathogenetic pathways based on these observations and are currently being developed and explored. Some of the novel pathogenetic aspects, however, already influence decision making in the clinic. [source] OCT4: biological functions and clinical applications as a marker of germ cell neoplasiaTHE JOURNAL OF PATHOLOGY, Issue 1 2007L Cheng Abstract Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the gonads as well as in extragonadal sites, that share morphological patterns and an overall good prognosis, owing to their responsiveness to current surgical, chemotherapeutic, and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features because of their close relationships with normal embryonal development as demonstrated by the pluripotentiality of some undifferentiated GCT variants. The similarities between GCTs and normal germ cell development have made it possible to identify possible pathogenetic pathways in neoplastic transformation and progression of GCTs. Genotypic and immunophenotypic profiles of these tumours are also useful in establishing and narrowing the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development of commercially available OCT4-specific antibodies suitable for immunohistochemistry on paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry is an additional helpful marker both in the differential diagnosis of specific histological subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in managing patients known to be at high risk for the development of invasive GCTs. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Patterns of severe abdominal wall defects: Insights into pathogenesis, delineation, and nomenclatureBIRTH DEFECTS RESEARCH, Issue 3 2007Liliana Vauthay Abstract BACKGROUND: During the last decade, descriptions of malformation complexes involving an abdominal wall defect (AWD) have repeatedly appeared in the literature, and there has been frequent confusion regarding nomenclature, definitions, and delineations. The aims of this work were to evaluate possible embryological relationships among AWD cases, review the related nomenclature, identify patterns involving AWDs, and stress the importance of complete clinical descriptions. METHODS Cases diagnosed as AWD complexes were selected from live- and stillborn infants of the Hospital Materno Infantil Sardá, Buenos Aires, and from the Laboratory of Perinatal Pathology, Buenos Aires, Argentina. They were sorted by the location of the AWD, the umbilical cord length, and the presence or absence of a persistent cloaca. The findings in 26 cases were described, according to proposed definitions. RESULTS: Three patterns could be identified: 1) the AWD involving the umbilical ring, a persistent or exstrophic cloaca, and a spinal cord anomaly; 2) the AWD extending laterally to the umbilical ring, severe unilateral limb defects, and same-sided agenesis of abdominal organs; and 3) the AWD not involving the umbilical ring, clefts, exencephaly, and amputations. Furthermore, overlapping among these patterns was observed, and possible involved mechanisms are discussed. CONCLUSIONS: The observed overlapping among patterns suggested that malformation complexes involving AWDs might not be independent conditions but rather belong to a common and broader spectrum of anomalies. Complete clinical descriptions, the avoidance of synonyms and generalizations, and strictly defined inclusion criteria are proposed for a better understanding of pathogenetic pathways in, and relationships among, AWD complexes. Birth Defects Research (Part A), 2007. © 2006 Wiley-Liss, Inc. [source] | ||||||||||