RESUMO
ATG2 proteins facilitate bulk lipid transport between membranes. ATG2 is an essential autophagy protein, but ATG2 also localizes to lipid droplets (LDs), and genetic depletion of ATG2 increases LD numbers while impairing fatty acid transport from LDs to mitochondria. How ATG2 supports LD homeostasis and whether lipid transport regulates this homeostasis remains unknown. Here we demonstrate that ATG2 is preferentially recruited to phospholipid monolayers such as those surrounding LDs rather than to phospholipid bilayers. In vitro, ATG2 can drive phospholipid transport from artificial LDs with rates that correlate with the binding affinities, such that phospholipids are moved much more efficiently when one of the ATG2-interacting structures is an artificial LD. ATG2 is thought to exhibit 'bridge-like" lipid transport, with lipids flowing across the protein between membranes. We mutated key amino acids within the bridge to form a transport-dead ATG2 mutant (TD-ATG2A) which we show specifically blocks bridge-like, but not shuttle-like, lipid transport in vitro. TD-ATG2A still localizes to LDs, but is unable to rescue LD accumulation in ATG2 knockout cells. Thus, ATG2 has a natural affinity for, and an enhanced activity upon LD surfaces and uses bridge-like lipid transport to support LD dynamics in cells.
RESUMO
Aim: Fundoplication fails in approximately 20% of children with severe neurodisability. We aimed to evaluate total esophagogastric dissociation (TOGD) as a primary procedure and as a 'rescue' procedure for severely neurologically impaired children with significant swallowing discoordination and gastroesophageal reflux disease. Methods: Casenotes of 40 children with severe neurodisability who underwent TOGD between 2005 and 2015 were retrospectively reviewed. Of these, 33 were primary procedures and 7 were 'rescue' procedures following failed fundoplication. Results: Median age at surgery was 3 years 7 months (range 1 month to 13 years 11 months). Preoperatively, all children had symptoms of regurgitation, retching or vomiting and 70% of children had an unsafe swallow. There were 5 early complications related to surgery in 4 children requiring surgical intervention. One child died following relaparotomy for esophagojejunal anastomotic breakdown because of multiorgan failure. Gastrostomy feeding was established by a median of 6 days (range 2 to 25 days) and median hospital stay was 10 days (range 4 to 280 days). There were 5 late complications. Median follow-up was 13 months (range 1 month to 8 years 4 months). All children have had resolution of gastroesophageal reflux. Thirteen percent of children experience bloating or pain on feeding and 26% of children experience retching unrelated to gastroesophageal reflux. There were 8 late deaths unrelated to surgery. Conclusion: TOGD should be considered as a primary and definitive procedure in selected severely neurodisabled children who are at higher risk of failure of fundoplication, recurrent aspiration and a reduced quality of life.
Assuntos
Transtornos de Deglutição/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Esôfago/cirurgia , Refluxo Gastroesofágico/cirurgia , Estômago/cirurgia , Adolescente , Anastomose Cirúrgica/efeitos adversos , Criança , Pré-Escolar , Transtornos de Deglutição/etiologia , Feminino , Refluxo Gastroesofágico/etiologia , Humanos , Lactente , Tempo de Internação , Masculino , Doenças do Sistema Nervoso/complicações , Qualidade de Vida , Estudos RetrospectivosRESUMO
Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.
Assuntos
Biomarcadores Tumorais/metabolismo , Queratina-7/metabolismo , Doença de Paget Extramamária/metabolismo , Doença de Paget Extramamária/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Virilha/patologia , Humanos , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Pênis/patologia , Prognóstico , Escroto/patologiaRESUMO
Imatinib mesylate, a tyrosine kinase inhibitor targeting the Bcr-Abl protein, c-kit (KIT) and the platelet-derived growth factor receptors (PDGFR), is an important part of the therapeutic armamentarium used in chronic myelogenous leukemia and gastrointestinal stromal tumors. A multitude of dermatological toxicities occur with the clinical use of this drug, ranging from various acute rashes to Steven-Johnson syndrome. Hyperpigmentation of the skin is a less frequent side effect. This phenomenon may be linked to alterations in the c-kit signaling pathway, which plays an important role in melanogenesis. A similar cutaneous phenotypic expression is manifested in families carrying congenital tyrosine II domain mutations of c-kit. We present a unique case of long-term persistent hyperpigmentation that occurred after the treatment with imatinib and describe the possible pathogenetic mechanisms involved. Elucidation of the mechanisms of action of imatinib in the skin may open future directions for the treatment of pigmentary disorders.
Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Hiperpigmentação/induzido quimicamente , Piperazinas/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/efeitos adversos , Benzamidas , Biópsia por Agulha , Doença Crônica , Relação Dose-Resposta a Droga , Esquema de Medicação , Seguimentos , Humanos , Hiperpigmentação/patologia , Mesilato de Imatinib , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Piperazinas/uso terapêutico , Proteínas Tirosina Quinases/efeitos adversos , Proteínas Tirosina Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Medição de RiscoRESUMO
This paper describes a collaborative project that joins academic perspectives and clinical practice perspectives in a focused clinical experience. This activity involves 3rd quarter associate degree nursing students in a medical-surgical course. Instructors identified the need to provide an activity to develop intravenous therapy skills and provide increased opportunities, thus increasing technical skill and assessment skills. This led to the development of the focused clinical experience. During this clinical rotation, the students rotate through either a Same Day Surgery unit or an endoscopy unit for one of their clinical days. The primary objective of this clinical day is to provide intravenous therapy. The duration of this project was a 10-week quarter of the curriculum and involved 38 students in the 2002 class and 30 in the 2003 class. Results indicate a very positive learning experience for the student, as well as a collaborative and contributing effort by the students for the staff. The staff, on the other hand, assists in providing a mentoring role in shared expertise. Collaborative partnerships between academia and practice can help bridge the gap by providing opportunities to share perceptions, creating an environment for shared knowledge, and networking opportunities, leading to further enabling preparation for potentially future staff.
Assuntos
Comportamento Cooperativo , Educação em Enfermagem/métodos , Internato não Médico/métodos , Desenvolvimento de Programas/métodos , Currículo , Educação em Enfermagem/organização & administração , Avaliação Educacional/métodos , Humanos , Internato não Médico/organização & administração , Ohio , Estudos de Casos Organizacionais , Avaliação de Programas e Projetos de Saúde , Ensino/métodosRESUMO
BACKGROUND: Keloids are exuberant, disfiguring scars that result from an abnormal healing process. Current established treatment strategies include surgical resection, triamcinolone steroid injection, pressure therapy, silicone therapy, and radiotherapy. None of these therapies, either alone or in combination, offers consistent recurrence-free rates above 70 to 80 percent. The antiproliferative, antifibrotic cytokine, interferon alpha-2b, may be useful in keloid management because of its ability to interfere with collagen synthesis and fibroblast proliferation. METHODS: To determine the efficacy of interferon alpha-2b in keloid management, the authors prospectively evaluated the effects of interferon alpha-2b as postexcisional adjuvant therapy for keloids. Thirty-nine keloids in 34 patients were photographed, measured, and surgically excised. The wound bed was injected twice with either interferon alpha-2b (treatment group; n = 13 keloids) or triamcinolone (control group; n = 26 keloids) at surgery and 1 week later. The patients were followed up in the plastic surgery clinic. RESULTS: The trial protocol was terminated at midtrial surveillance. Among the 13 keloids that were treated with postoperative intralesional interferon alpha-2b, seven recurred (54 percent recurrence rate). In contrast, in the 26 keloids that received triamcinolone (control group), only four recurred (15 percent recurrence rate). Recurrence in either group did not correlate with location of the keloid or race. CONCLUSION: Interferon does not appear to be effective in the clinical management of keloids.
Assuntos
Interferon-alfa/uso terapêutico , Queloide/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Queloide/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Recidiva , Falha de Tratamento , Triancinolona/uso terapêuticoRESUMO
BACKGROUND: Nevus sebaceus of Jadassohn (NS) has the classic presentation on the head and neck of a yellow-orange-colored, waxy, pebble-like, papule or plaque. Its reported malignant potential varies between 0.8% and 50%. The common location of NS on the temporal hairline leaves a cosmetic defect. METHODS: We retrospectively reviewed a consecutive series of patients with NS located in the temporal scalp region. Thirteen patients were included. Twelve patients were reconstructed with a temporal flap. One patient had a primary linear scalp closure after excision. Clinical, histopathologic, surgical, and photographic records were used to review the clinical, anatomic, and pathologic presentation of the lesions. Reconstructions were rated on a scale of 1-5 by two independent examiners. The cosmetic results were also assessed by the patients. RESULTS: Patients ranged in age from 3 to 40 years. All of the lesions were located in the temporal area of the scalp. All cases were pathologically determined as NS. Two cases contained basal cell carcinoma (15%). Two cases were re-excisions of confirmed NS. One case was excised and closed with difficulty using a linear primary closure. Rotation flaps based on the superior temporal artery were used for the reconstruction of the defects in 12 patients. Nine of the flaps were anterior rotation flaps and three were posterior. The average score for the cosmetic results of the patients was 3.75, with the lowest score being 2, and the highest 5. The score for the linear closure was 2. CONCLUSION: A rotation flap based on the superficial temporal artery is an excellent reconstructive solution for NS located in the temporal scalp region.