Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Neuropathol Appl Neurobiol ; 48(2): e12771, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34648194

RESUMEN

AIMS: TRAPPC11, a subunit of the transport protein particle (TRAPP) complex, is important for complex integrity and anterograde membrane transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported with muscle weakness and other features including brain, liver, skeletal and eye involvement. A detailed analysis of brain and muscle pathology will further our understanding of the presentation and aetiology of TRAPPC11 disease. METHODS: We describe five cases of early-onset TRAPPC11-related muscular dystrophy with a systematic review of muscle pathology in all five individuals, post-mortem brain pathology findings in one and membrane trafficking assays in another. RESULTS: All affected individuals presented in infancy with muscle weakness, motor delay and elevated serum creatine kinase (CK). Additional features included cataracts, liver disease, intellectual disability, cardiomyopathy, movement disorder and structural brain abnormalities. Muscle pathology in all five revealed dystrophic changes, universal hypoglycosylation of alpha-dystroglycan and variably reduced dystrophin-associated complex proteins. Membrane trafficking assays showed defective Golgi trafficking in one individual. Neuropathological examination of one individual revealed cerebellar atrophy, granule cell hypoplasia, Purkinje cell (PC) loss, degeneration and dendrite dystrophy, reduced alpha-dystroglycan (IIH6) expression in PC and dentate neurones and absence of neuronal migration defects. CONCLUSIONS: This report suggests that recessive mutations in TRAPPC11 are linked to muscular dystrophies with hypoglycosylation of alpha-dystroglycan. The structural cerebellar involvement that we document for the first time resembles the neuropathology reported in N-linked congenital disorders of glycosylation (CDG) such as PMM2-CDG, suggesting defects in multiple glycosylation pathways in this condition.


Asunto(s)
Encéfalo/metabolismo , Distroglicanos/metabolismo , Músculo Esquelético/metabolismo , Distrofias Musculares/genética , Proteínas de Transporte Vesicular/genética , Preescolar , Femenino , Glicosilación , Humanos , Lactante , Hígado/metabolismo , Masculino , Distrofias Musculares/metabolismo , Mutación , Proteínas de Transporte Vesicular/metabolismo
2.
3.
Surgeon ; 11(2): 63-6, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22281369

RESUMEN

BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the standard of care in axillary staging of clinically node-negative breast cancer patients. AIMS: To analyze reasons for failure of SLN localization by means of a multivariate analysis of clinical and histopathological factors. METHODS: We performed a review of 164 consecutive breast cancer patients who underwent SLNB. A superficial injection technique was used. RESULTS: 9/164 patients failed to show nodes. In 7/9 patients no evidence of radioactivity or blue dye was observed. Age and nodal status were the only statistically significant factors (p < 0.05). For every unit increase in age there was a 9% reduced chance of failed SLN localization. Patients with negative nodal status have 90% reduced risk of failed sentinel node localization than patients with macro or extra capsular nodal invasion. DISCUSSION: The results suggest that altered lymphatic dynamics secondary to tumour burden may play a role in failed sentinel node localization. We showed that in all failed localizations the radiocolloid persisted around the injection site, showing limited local diffusion only. While clinical and histopathological data may provide some clues as to why sentinel node localization fails, we further hypothesize that integrity of peri-areolar lymphatics is important for successful localization.


Asunto(s)
Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Factores de Edad , Anciano , Axila , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Cintigrafía , Estudios Retrospectivos
4.
J Med Chem ; 59(10): 4926-47, 2016 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-27077528

RESUMEN

Transient receptor potential vanilloid 3 (TRPV3) is a Ca(2+)- and Na(+)-permeable channel with a unique expression pattern. TRPV3 is found in both neuronal and non-neuronal tissues, including dorsal root ganglia, spinal cord, and keratinocytes. Recent studies suggest that TRPV3 may play a role in inflammation, pain sensation, and skin disorders. TRPV3 studies have been challenging, in part due to a lack of research tools such as selective antagonists. Herein, we provide the first detailed report on the development of potent and selective TRPV3 antagonists featuring a pyridinyl methanol moiety. Systematic optimization of pharmacological, physicochemical, and ADME properties of original lead 5a resulted in identification of a novel and selective TRPV3 antagonist 74a, which demonstrated a favorable preclinical profile in two different models of neuropathic pain as well as in a reserpine model of central pain.


Asunto(s)
Ciclobutanos/síntesis química , Ciclobutanos/farmacología , Piridinas/síntesis química , Piridinas/farmacología , Canales Catiónicos TRPV/antagonistas & inhibidores , Calcio/metabolismo , Ciclobutanos/química , Relación Dosis-Respuesta a Droga , Células HEK293 , Humanos , Conformación Molecular , Piridinas/química , Relación Estructura-Actividad , Canales Catiónicos TRPV/metabolismo
5.
Hastings Cent Rep ; 33(1): 27-33, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12613385

RESUMEN

Proposals to compensate families for transplantable organs are gathering momentum. The proposals assume that the body is dissociable from the self and can be treated like property. But such a view is out of step with the rest of the culture.


Asunto(s)
Cultura , Trasplante de Órganos/economía , Obtención de Tejidos y Órganos/economía , Bioética , Comercio , Humanos , Motivación , Trasplante de Órganos/legislación & jurisprudencia , Valores Sociales , Donantes de Tejidos/legislación & jurisprudencia , Obtención de Tejidos y Órganos/legislación & jurisprudencia , Estados Unidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA