المؤلفون: Steagall, Wendy K, Pacheco-Rodriguez, Gustavo, Darling, Thomas N, Torre, Olga, Harari, Sergio, Moss, Joel

المساهمون: W.K. Steagall, G. Pacheco-Rodriguez, T.N. Darling, O. Torre, S. Harari, J. Moss

مصطلحات موضوعية: TSC2, loss of heterozygosity, lymphangioleiomyomatosi, tuberous sclerosi, Female, Gene Expression Regulation, Neoplastic, Human, Lung Neoplasm, Mutation, Skin, Tumor Cells, Cultured, Settore MED/11 - Malattie dell'Apparato Cardiovascolare

الوصف: Lymphangioleiomyomatosis (LAM) is a multisystem disease of women, affecting lungs, kidneys, and lymphatics. It is caused by the proliferation of abnormal smooth muscle-like LAM cells, with mutations and loss of heterozygosity in the TSC1 or, more frequently, TSC2 genes. Isolated pulmonary LAM cells have been difficult to maintain in culture, and most studies of LAM lung cells involve mixtures of TSC2 wild-type and TSC2-null cells. A clonal population of LAM lung cells has not been established, making analysis of the cells challenging. Cell lines have been established from angiomyolipomas, a common manifestation of LAM, and from tumors from patients with TSC. Circulating LAM cells have also been isolated from blood and other body fluids. LAM cells may also be identified in clusters apparently derived from lymphatic vessels. Genetics, patterns of antigen expression, and signaling pathways have been studied in LAM lung tissue and in LAM cell models, although rarely all in the same study. We show here that LAM cells manifest differences in these characteristics, depending on the source investigated, suggesting further studies.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29406787; info:eu-repo/semantics/altIdentifier/wos/WOS:000433972100005; volume:58; issue:6; firstpage:678; lastpage:683; numberofpages:6; journal:AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY; http://hdl.handle.net/2434/748541Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85048227924

الإتاحة: https://doi.org/10.1165/rcmb.2017-0403TRTest
http://hdl.handle.net/2434/748541Test

المؤلفون: Peron A., Au K. S., Northrup H.

المساهمون: A. Peron, K.S. Au, H. Northrup

مصطلحات موضوعية: genetic counseling, genetics of TSC, genotype–phenotype correlation, TSC1, TSC2, tuberous sclerosis complex (TSC), Genetic Association Studie, Genetic Testing, Human, Mosaicism, Mutation, Pedigree, Precision Medicine, TOR Serine-Threonine Kinase, Tuberous Sclerosi, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Settore MED/03 - Genetica Medica

الوصف: Tuberous Sclerosis Complex (TSC) is a multisystem autosomal dominant condition caused by inactivating pathogenic variants in either the TSC1 or the TSC2 gene, leading to hyperactivation of the mTOR pathway. Here, we present an update on the genetic and genomic aspects of TSC, with a focus on clinical and laboratory practice. We briefly summarize the structure of TSC1 and TSC2 as well as their protein products, and discuss current diagnostic testing, addressing mosaicism. We consider genotype–phenotype correlations as an example of precision medicine, and discuss genetic counseling in TSC, with the aim of providing geneticists and health care practitioners involved in the care of TSC individuals with useful tools for their practice.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/30255984; info:eu-repo/semantics/altIdentifier/wos/WOS:000448788500003; volume:178; issue:3; firstpage:281; lastpage:290; numberofpages:10; journal:AMERICAN JOURNAL OF MEDICAL GENETICS. PART C, SEMINARS IN MEDICAL GENETICS; http://hdl.handle.net/2434/760064Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85053903775

الإتاحة: https://doi.org/10.1002/ajmg.c.31651Test
http://hdl.handle.net/2434/760064Test

المؤلفون: ALESI, NICOLA

المساهمون: Alesi, Nicola, PROCOPIO, Antonio Domenico

مصطلحات موضوعية: tuberous Sclerosi, TSC2, osteoclast, bone lesion, CTHRC1, Settore MED/04 - Patologia Generale

الوصف: La maggior parte dei pazienti affetti da Sclerosi Tuberosa mostra lesioni ossee di tipo sclerotico, la cui patogenesi e’ sconosciuta. Le lesioni sclerotiche potrebbero rappresentare un eccessivo e focale accumulo di osso. Lo scheletro e’ continuamente rimodellato dall’azione di osteoblasti, le cellule che producono tessuto osseo e osteoclasti (OC), che lo degradano. Evidenze dimostrano che la perdita di TSC1 o TSC2 negli osteoblasti ha effetto negativo nella maturazione dello scheletro, ma la funzione del complesso TSC1-TSC2 negli OC non e’ noto. Per identificare il ruolo di TSC2 negli OC abbiamo incrociato un topo CtskCRE, in cui Cre e’ espresso negli OC, con un topo Tsc2fl/fl per generare un topo CtskCre; Tsc2fl/fl ora in avanti chiamato Tsc2ΔOC. I topi Tsc2ΔOC maschi presentano un incremento di 3 volte della quantita’ di osso trabecolare a 9 mesi di eta’ (p< 0.01), cosi’ come dello spessore della corticale ossea (1.5 volte, p<0.05). Caratteristiche simili sono osservate a 3 mesi di eta’. Come pronosticato, gli OC derivati da topi Tsc2ΔOC hanno elevazione di mTORC1 ma presentano una normale maturazione ed una normale attivita’ secretoria in vitro. Per studiare la funzione degli OC in vivo, abbiamo misurato i livelli sierici di CTX1, un marker della loro attivita’, trovandolo normale sia nei topi maschi che nelle femmine a 3 mesi di eta’, normale nelle femmine a 9 mesi di eta’ ed aumentato nei maschi a 9 mesi di eta’. La concentrazione sierica di P1NP, un marker di attivita’ degli osteoblasti e’ stata trovata elevata in tutti i gruppi considerati. Gli OC aumentano l’attivita’ degli osteoblasti mediante la secrezione di clastochine, un meccanismo chiamato coupling. L’ RNA messaggero di CTHRC1 (una clastochina) e’ aumentato di 11 volte (p<0.001) nei femori di topi Tsc2ΔOC a 3 mesi cosi come a 9 mesi di eta’. Il nostro modello suggerisce che la perdita di TSC2 negli OC possa stimolare gli osteoblasti a produrre osso tramite la mTORC1 dipendente secrezione di CTHRC1. ; The majority of TSC patients have ...

العلاقة: http://hdl.handle.net/11566/245595Test

الإتاحة: http://hdl.handle.net/11566/245595Test

المؤلفون: Paola Contini, Marco Barberis, Alberto Cavazza, Valerio Di Scioscio, Robin M. T. Cooke, Mario Schiavina, Walter F. Grigioni, Andrea Fabiani, Alessandro Bini, Antonia D’Errico-Grigioni, Annalisa Altimari

المساهمون: Schiavina, Mario, Di Scioscio, Valerio, Contini, Paola, Cavazza, Alberto, Fabiani, Andrea, Barberis, Marco, Bini, Alessandro, Altimari, Annalisa, Cooke, Robin M., Grigioni, Franco, D'Errico, Antonietta

مصطلحات موضوعية: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pathology, congenital, hereditary, and neonatal diseases and abnormalities, Histopathology, Loss of Heterozygosity, Sex Factor, Critical Care and Intensive Care Medicine, Tuberous Sclerosis Complex 1 Protein, Neoplasm Protein, Tuberous sclerosis, Germline mutation, Sex Factors, Tuberous Sclerosis, Antigens, Neoplasm, Lymphangioleiomyomatosi, Intensive care, hemic and lymphatic diseases, Progesterone receptor, Tuberous Sclerosis Complex 2 Protein, medicine, Humans, Lymphangioleiomyomatosis, Tumor Suppressor Protein, business.industry, Tumor Suppressor Proteins, Pneumothorax, medicine.disease, Immunohistochemistry, Neoplasm Proteins, medicine.anatomical_structure, Smooth muscle cell, Tuberous Sclerosi, Sex distribution, TSC1, TSC2, business, Melanoma-Specific Antigen, Tomography, X-Ray Computed, Melanoma-Specific Antigens, Rare disease, Human

الوصف: Rationale: The three previously reported cases of conclusively documented pulmonary lymphangioleiomyomatosis (LAM) in men were associated with definite or probable tuberous sclerosis complex (TSC). Objectives: To describe an unequivocal case of pulmonary LAM occurring in a man with no clinical or genotypic evidence of TSC. Methods: At high-resolution computed tomography, a 37-year-old phenotypically and karyotypically normal man with left pneumothorax and massive pulmonary collapse had widespread thin-walled cysts throughout both lungs. Histological diagnosis of LAM was performed on biopsy material, and immunohistochemically confirmed with the HMB-45 monoclonal antibody. Measurements and Main Results: Remarkably, the HMB-45-positive cells lining the cysts also showed strong reactivity for estrogen and progesterone receptor proteins. TSC was clinically excluded, and TSC1 and TSC2 germline mutations were not detected at DNA analysis. Conclusions: This article indicates that occurrence of LAM may be possible in a chromosomally normal man unaffected by TSC. On diagnostic grounds, the possibility of LAM should be borne in mind when diffuse cystic lung disease occurs in aman, even in the absence of signs of TSC.

وصف الملف: STAMPA

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3788685a1936e903117bcc33a33f6b1bTest
http://hdl.handle.net/11585/74082Test