Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the case of a 39-year-old man who underwent repair of a symptomatic 5-cm abdominal aortic aneurysm. This patient had received a bilateral lung transplant for cystic fibrosis 10 years before this event. He was receiving cyclosporine, prednisone, and azathioprine as immunosuppression therapy. To our knowledge, this is the first reported abdominal aortic aneurysm after lung transplantation, and we note that our patient had a rapidly enlarging aneurysm, as seen in recipients of heart transplants. We postulate that immunosuppression may be related to the development and/or rapid growth of abdominal aortic aneurysms.
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PMID:Abdominal aortic aneurysm after pulmonary transplantation: a case report. 1070 73

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis. The most common mutation, DeltaF508 CFTR, is retained in the endoplasmic reticulum, retrotranslocated into the cytosol, and degraded by the proteasome. In a proteomics screen to identify DeltaF508 CFTR interacting proteins, we found that valosin-containing protein (VCP)/p97, a Type II AAA ATPase that is a component of the retrotranslocation machinery, binds DeltaF508 CFTR, and this interaction is stabilized by proteasomal inhibition. Since wild-type (WT) CFTR has been reported to be inefficiently processed during biogenesis with as much as 75% of the newly synthesized protein degraded by the proteasome, we examined the VCP interaction in Calu-3, T-84, and 16HBE, three epithelial cell lines that endogenously express WT CFTR. The results indicate that when WT CFTR processing is efficient, as demonstrated in Calu-3 cells, VCP does not interact. Interestingly, overexpression of recombinant WT CFTR in Calu-3 cells results in inefficient processing and VCP interaction, demonstrating that CFTR processing efficiency and the VCP interaction are tightly coupled. Furthermore, induction of ER stress and activation of the unfolded protein response result in inefficient processing of WT CFTR in Calu-3 cells and promote the WT CFTR-VCP interaction. The results support the hypothesis that components of the retrotranslocation machinery such as VCP do not interact with CFTR in epithelial cells that endogenously express WT CFTR, since under normal conditions the processing of the WT protein is efficient.
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PMID:VCP/p97 AAA-ATPase does not interact with the endogenous wild-type cystic fibrosis transmembrane conductance regulator. 1727 22

p97/VCP, a member of the AAA-ATPase super family, has been associated with a wide variety of essential cellular protein pathways com prising: (i) nuclear envelope reconstruction, (ii) cell cycle, (iii) Golgi reassembly, (iv) suppression of apoptosis and (v) DNA-damage response [1-6]. In addition, vasolin-containing protein (VCP) dislodges the ubiquitinated proteins from the endoplasmic reticulum (ER) and chaperones them to the cytosol for proteasomal degradation by endoplasmic reticulum-associated degradation (ERAD) [7]. The interactions of VCP in the endoplasmic reticulum-associated degradation (ERAD) pathway determine the substrate selection for proteasomal degradation. Moreover, the interaction with VCP is also required for the ubiquitination of substrate. VCP is phosphorylated by the master cellular kinase, Akt as a mechanism to regulate ERAD [8]. These multiple interactions in protein degradation pathways points to central role of VCP in misfolded protein degradation. VCP has a polyglutamine and ubiquitin-binding capacity and is involved in proteasomal degradation, cytosolic aggregation and processing of polyQ and polyUb aggregates in neurodegenerative and other misfolded protein diseases [9, 10]. Mutations in VCP gene are also linked to a protein deposition disorder, IBMFD [11]. We propose VCP as a therapeutic target for diseases caused by cytosolic protein aggregation or degradation of misfolded protein. We predict that selective interference of VCP interaction(s) with aberrant protein or its ERAD function will be an effective therapeutic site to rescue functional misfolded protein in diseases like cystic fibrosis and alpha-1-trypsin deficiency. The control of VCP expression is also proposed to be a potential therapeutic target in ex-polyQ-induced neurodegenerative diseases [12]. The further functional characterization of VCP and associated proteins in these diseases will help in designing of selective therapeutics.
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PMID:AAA ATPase p97/VCP: cellular functions, disease and therapeutic potential. 1879 39

Cystic fibrosis patients are frequently plagued by infections, often with unusual or hardy organisms. Their infections are only complicated by transplantation. In this report, we review the case of a young woman who had a double lung transplant secondary to cystic fibrosis who developed a lumbar osteomyelitis/discitis several years after transplantation. After treatment, she went on to develop a mycotic abdominal aortic aneurysm. The patient underwent thoracic and abdominal aortic replacement, and histopathology revealed Scedosporium apiospermum infection. The patient recovered well from surgery and was discharged home on long-term antifungal therapy. This represents the first reported case of S apiospermum mycotic aneurysm in a lung transplant patient, and possibly the largest number and longest duration of S apiospermum infections reported in a single patient.
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PMID:Case report of vertebral osteomyelitis and mycotic abdominal aortic aneurysm caused by Scedosporium apiospermum in a lung transplant patient with cystic fibrosis. 2564 5