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【medical-news】杵状指到底向我们泄露了什么？
By Steve Mitchell
ScienceNOW Daily News
27 May 2008
Club-shaped fingers can be a warning sign for serious lung and heart conditions, but the cause of the disorder has remained a mystery for more than 2400 years. Now, researchers may have taken a step toward solving the puzzle by pinpointing the mutation that spurs a rare type of clubbing.
Clubbing, or swelling of the fingertips, is one of the first symptoms medical students are taught to look for because it can signal lung cancer, heart disease, or other grave conditions. The father of medicine himself, Hippocrates, first described clubbing about 450 B.C.E., but researchers have yet to figure out what triggers the swelling.
Seeking a genetic clue, a team led by David Bonthron, a clinical geneticist at the University of Leeds, U.K., went looking for the DNA glitch behind primary hypertrophic osteoarthropathy (PHO). The rare condition, which accounts for only 3% to 5% of clubbing cases, results in enlarged fingertips and joint pain but does not cause the other underlying disorders--although some patients also develop heart disease.
Bonthron's team scanned the genomes of six PHO patients from three different families and found that they all had a mutation in the HPGD gene. The gene encodes an enzyme that breaks down prostaglandins, hormonelike molecules that promote inflammation and help regulate fluid balance and blood flow--processes that could affect clubbing. Further examination showed that the patients had higher-than-normal levels of a prostaglandin called PGE2, confirming that the mutation leads to a faulty enzyme that doesn't properly break down prostaglandins, the researchers report this week in Nature Genetics. The finding suggests that a urine test for elevated prostaglandin levels could help doctors diagnose this type of clubbing and that the condition could be reversed with existing drugs that block prostaglandins.
Overproduction of prostaglandins could also be the cause of the clubbing associated with lung cancer, heart disease, and other illnesses, Bonthron says. Although patients with these ailments don't have the HPGD mutation, he explains, other aspects of their conditions, such as the tumors that occur with lung cancer, trigger a rise in prostaglandins.
Manual Martinez-Lavin, a rheumatologist at the National Institute of Cardiology in Mexico City, Mexico, agrees that the finding could offer insight about the cause of other forms of clubbing. But he doubts that elevated prostaglandins directly produce finger swelling. That's because the compounds have been used to treat peptic ulcers, and there is no indication of finger abnormalities in these patients, he notes.
Instead, says Martinez-Lavin, elevated levels of prostaglandins might somehow enable another molecule called vascular endothelial growth factor (VEGF) to cause clubbing. Previous studies have shown that PHO patients have elevated levels of VEGF, which can trigger symptoms of clubbing, including the accumulation of fluid, he says.
http://sciencenow.sciencemag.org/cgi/content/full/2008/527/2 Club-shaped fingers can be a warning sign for serious lung and heart conditions, but the cause of the disorder has remained a mystery for more than 2400 years. Now, researchers may have taken a step toward solving the puzzle by pinpointing the mutation that spurs a rare type of clubbing.
杵状指可能是严重心肺疾病的一个信号。但是杵状指形成的原因2400多年来仍是个谜。目前，
研究者的发现进一步揭示了该谜题，他们指出某基因的突变导致了一种稀有类型的杵状指的发生。
Clubbing, or swelling of the fingertips, is one of the first symptoms medical students are taught to look for because it can signal lung cancer, heart disease, or other grave conditions. The father of medicine himself, Hippocrates, first described clubbing about 450 B.C.E., but researchers have yet to figure out what triggers the swelling.
杵状指或者说指尖水肿是医学生们最先认识的一种提示肺肿瘤，心脏病或者其他严重疾病的症状。医学之父希波格拉底在早在公元前４５０年首先描述了该症状，但是研究者们至今才指出是什么引发了水肿。
Seeking a genetic clue, a team led by David Bonthron, a clinical geneticist at the University of Leeds, U.K., went looking for the DNA glitch behind primary hypertrophic osteoarthropathy (PHO). The rare condition, which accounts for only 3% to 5% of clubbing cases, results in enlarged fingertips and joint pain but does not cause the other underlying disorders--although some patients also develop heart disease.
为了发现基因方面的线索，英国丽兹大学遗传学家David Bonthron带领的小组企图在原发性肥大性骨关节病的患者上找到某些基因的变异。然而这种基因变异的情况只发生在３％－５％的杵状指患者中，并且只引起指尖增粗和关节疼痛而没有引起其他潜在的病变——虽然一些患者也有心脏病。，
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作者:admin@医学,生命科学 2011-08-13 05:14
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