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51.
Higuera Alvarez R Sanso Sureda A Sapiña Camaro A Gómez Cedenilla A 《Gastroenterologia y hepatologia》2008,31(8):497-499
Eosinophilic esophagitis is a rare, recently discovered disease, characterized by esophageal symptoms, such as dysphagia and food impaction, associated with dense eosinophilia on endoscopic biopsy of the esophagus. Other entities such as gastroesophageal reflux disease are absent and there is a lack of response to proton pump inhibitor therapy. This disease mainly affects the pediatric population but is becoming more prevalent in adults. There are several theories on the etiopathogenesis of this entity, which may involve allergies and atopy. In advanced disease, complications such as esophageal stenosis can appear. Treatment is based on dietary elimination, corticosteroids and endoscopic dilatation. We report a case of eosinophilic esophagitis with esophageal stenosis. 相似文献
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Pinós Tomàs Fuku Noriyuki Cámara Yolanda Arai Yasumichi Abe Yukiko Rodríguez-Romo Gabriel Garatachea Nuria Santos-Lozano Alejandro Miro-Casas Elisabet Ruiz-Meana Marisol Otaegui Imanol Murakami Haruka Miyachi Motohiko Garcia-Dorado David Hinohara Kunihiko Andreu Antoni L. Kimura Akinori Hirose Nobuyoshi Lucia Alejandro 《Age (Dordrecht, Netherlands)》2014,36(2):933-943
GeroScience - The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery... 相似文献
53.
Jordon M. Inloes Ku-Lung Hsu Melissa M. Dix Andreu Viader Kim Masuda Thais Takei Malcolm R. Wood Benjamin F. Cravatt 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(41):14924-14929
Complex hereditary spastic paraplegia (HSP) is a genetic disorder that causes lower limb spasticity and weakness and intellectual disability. Deleterious mutations in the poorly characterized serine hydrolase DDHD2 are a causative basis for recessive complex HSP. DDHD2 exhibits phospholipase activity in vitro, but its endogenous substrates and biochemical functions remain unknown. Here, we report the development of DDHD2−/− mice and a selective, in vivo-active DDHD2 inhibitor and their use in combination with mass spectrometry-based lipidomics to discover that DDHD2 regulates brain triglycerides (triacylglycerols, or TAGs). DDHD2−/− mice show age-dependent TAG elevations in the central nervous system, but not in several peripheral tissues. Large lipid droplets accumulated in DDHD2−/− brains and were localized primarily to the intracellular compartments of neurons. These metabolic changes were accompanied by impairments in motor and cognitive function. Recombinant DDHD2 displays TAG hydrolase activity, and TAGs accumulated in the brains of wild-type mice treated subchronically with a selective DDHD2 inhibitor. These findings, taken together, indicate that the central nervous system possesses a specialized pathway for metabolizing TAGs, disruption of which leads to massive lipid accumulation in neurons and complex HSP syndrome.Determining the genetic basis for rare hereditary human diseases has benefited from advances in DNA sequencing technologies (1). As a greater number of disease-causing mutations are mapped, however, it is also becoming apparent that many of the affected genes code for poorly characterized proteins. Assigning biochemical and cellular functions to these proteins is critical to achieve a deeper mechanistic understanding of human genetic disorders and for identifying potential treatment strategies.Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurologic syndrome marked by spasticity and lower extremity weakness (2). Many genetic types of HSP have been identified and are numbered according to their order of discovery [spastic paraplegia (SPG) 1-72] (2, 3). Of these genetic variants, more than 40 have been mapped to causative mutations in protein-coding genes. HSP genes code for a wide range of proteins that do not conform to a single sequence- or function-related class. A subset of HSP genes, including PNPLA6 (or neuropathy-target esterase) (SPG39) (4), DDHD1 (SPG28) (5), and DDHD2 (SPG54) (3, 6–8), code for serine hydrolases. These enzymes have been designated as (lyso)phospholipases based on in vitro substrate assays (9–11), but their endogenous substrates and physiological functions remain poorly understood. The mutational landscape that affects these lipid hydrolases to cause recessive HSP is complex but collectively represents a mix of null and putatively null and/or functional mutations. Moreover, the type of HSP appears to differ in each case, with DDHD1 mutations causing uncomplicated HSP, whereas PNPLA6 and DDHD2 mutations lead to complex forms of the disease that exhibit additional phenotypes including, in the case of DDHD2, intellectual disability. Human subjects with DDHD2 mutations also displayed evidence of brain lipid accumulation as detected by cerebral magnetic resonance spectroscopy (6). Both rodent and human DDHD2 enzymes are highly expressed in the brain compared with most peripheral tissues (6, 9); however, the specific lipids regulated by DDHD2 in the central nervous system (CNS) have not yet been identified.Determining the metabolic function of DDHD2 in the brain is an important step toward understanding how mutations in this enzyme promote complex HSP and for identifying possible therapeutic strategies for the disease. Toward this end, we report herein the generation and characterization of DDHD2−/− mice and a selective DDHD2 inhibitor. DDHD2−/− mice exhibit defects in movement and cognitive function. Mass spectrometry (MS)-based lipidomics (12, 13) revealed a striking and selective elevation in triglycerides (triacylglycerols, or TAGs) throughout the CNS, but not in peripheral tissues, of DDHD2−/− mice. This metabolic change correlated with pervasive lipid droplet (LD) accumulation in neuronal cell bodies of DDHD2−/− mice. Biochemical assays confirmed that DDHD2 possesses TAG hydrolase activity. Finally, wild-type mice treated subchronically with a DDHD2 inhibitor also exhibited significant elevations in CNS TAGs. These data, taken together, indicate that DDHD2 is a principal TAG hydrolase of the mammalian brain and point to deregulation of this pathway as a major contributory factor to complex HSP. 相似文献
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Abdominal Radiology - There is discrepancy in the literature regarding the optimal dose of gadobenate for liver MRI. We evaluated the quality of liver MRIs performed in the same individual using... 相似文献
56.
Piñol V Andreu M Castells A Payá A Bessa X Rodrigo J;Gastrointestinal Oncology Group of the Spanish Gastroenterological Association 《European journal of gastroenterology & hepatology》2004,16(1):39-45
BACKGROUND: Colorectal cancer is the third leading cause of cancer mortality in Western countries. Hereditary nonpolyposis colorectal cancer is the most common type of hereditary colorectal cancer, but its incidence remains controversial, ranging from 1 to 5%. OBJECTIVE: This present prospective, multicentre, nationwide study was aimed at compiling prominent epidemiological and clinical data with respect to hereditary non-polyposis colorectal cancer and other familial colorectal cancer forms in Spain, where information is lacking. METHODS: All patients with a de-novo diagnosis of colorectal cancer and who attended between November 2000 and October 2001 in 25 hospitals all over Spain were registered. Demographic, clinical and tumour-related characteristics of probands, and detailed family history, were obtained. RESULTS: A total of 1872 colorectal cancer patients were included. Clinical diagnosis of hereditary non-polyposis colorectal cancer was established in 46 (2.5%) patients according to the Amsterdam II criteria. Comparison between patients fulfilling either the Amsterdam I or the Amsterdam II criteria revealed no differences with respect to demographic, clinical and tumour-related characteristics. A total of 504 (27.0%) patients had a family history of hereditary non-polyposis colorectal cancer-related neoplasm not fulfilling the Amsterdam criteria (familial colorectal cancer), while 360 (19.2%) patients fulfilled at least one of the Bethesda's criteria. CONCLUSION: These clinicoepidemiological data provide a more accurate characterization of hereditary non-polyposis colorectal cancer and other familial colorectal cancer forms in Spain, with potential implications in preventive strategies. 相似文献
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Fernández-Castro M Andreu JL Muñoz P Silva L 《Rheumatology (Oxford, England)》2005,44(8):1076-7; author reply 1075
SIR, We read with interest the article of Ledingham and Deighton[1] updating the guidelines for prescribing TNF- blockers inadults with rheumatoid arthritis. The guidelines establish thatthe sepsis of a prosthetic joint that remains in situ is animportant exclusion criterion for 相似文献