Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FAP is characterized by progressive polyneuropathy and autonomic dysfunction and the latter consists of marked orthostatic hypotension, disturbed bowel movement, impotence and urinary incontinence. All these autonomic symptoms severely affect patient's daily activity. The precursor protein of amyloid fibrils in this disease is a variant form of transthyretin (TTR) in serum. Since TTR is produced mainly in the liver, liver transplantation has been employed for FAP patients as only one curative treatment. During the past 12 years more than 50 FAP patients underwent liver transplantation in Japan and the five-year survival rate of them was 77%. Early intervention (less than 5 years after onset) can provide a better chance of improving patients' condition after transplantation and gastrointestinal autonomic symptoms that include severe episodic nausea, vomiting, and alternating constipation and diarrhea significantly relieve shortly after operation. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Among them the presence of an autonomic failure in FAP patients seems to be contraindication for this challenging operation.
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PMID:[Autonomic dysfunction in FAP: its therapeutic effect by liver transplantation]. 1743 6

Amyloidosis is a group of disorders that can manifest in virtually any organ system in the body and is thought to be secondary to misfolding of extracellular proteins with subsequent deposition in tissues. The precursor protein that is produced in excess defines the specific amyloid type. This requires histopathological confirmation using Congo red dye with its characteristic demonstration of green birefringence under cross-polarized light. Gastrointestinal (GI) manifestations are common and the degree of organ involvement dictates the symptoms that a patient will experience. The small intestine usually has the most amyloid deposition within the GI tract. Patients generally have nonspecific findings such as abdominal pain, nausea, diarrhea, and dysphagia that can often delay the proper diagnosis. Liver involvement is seen in a majority of patients, although symptoms typically are not appreciated unless there is significant hepatic amyloid deposition. Pancreatic involvement is usually from local amyloid deposition that can lead to type 2 diabetes mellitus. In addition, patients may undergo either endoscopic or radiological evaluation; however, these findings are usually nonspecific. Management of GI amyloidosis primarily aims to treat the underlying amyloid type with supportive measures to alleviate specific GI symptoms. Liver transplant is found to have positive outcomes, especially in patients with specific variants of hereditary amyloidosis.
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PMID:Amyloidosis of the gastrointestinal tract and the liver: clinical context, diagnosis and management. 2736 50

Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with known functions, many peptides have been identified in mammalian brain for which the cognate receptors have not been identified. Similarly, dozens of "orphan" G protein-coupled receptors have been identified in the mammalian genome. While it would seem straightforward to match the orphan peptides and receptors, this is not always easily accomplished. In this review we focus on peptides named PEN and big LEN, which are among the most abundant neuropeptides in mouse brain, and their recently identified receptors: GPR83 and GPR171. These receptors are co-expressed in some brain regions and are able to interact. Because PEN and big LEN are produced from the same precursor protein and co-secreted, the interaction of GPR83 and GPR171 is physiologically relevant. In addition to interactions of these two peptides/receptors, PEN and LEN are co-localized with neuropeptide Y and Agouti-related peptide in neurons that regulate feeding. In this review, using these peptide receptors as an example, we highlight the multiple modes of regulation of receptors and present the emerging view that neuropeptides function combinatorially to generate a network of signaling messages. The complexity of neuropeptides, receptors, and their signaling pathways is important to consider both in the initial deorphanization of peptides and receptors, and in the subsequent development of therapeutic applications.
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PMID:Orphan neuropeptides and receptors: Novel therapeutic targets. 2917 50