Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited m...Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation. Methods The patient＇s LDL-R gene coding region was sequenced. The patient＇s lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient＇s heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging （MPI）. Results The patient＇s LDL-R expression, LDL binding and up-take functions were significantly lower than normal control （39%, 63% and 76% respectively）. A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes. Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.展开更多
Background It has been widely observed that infants and young children can reossify large calvarial defects when they are younger than 2 years of age; afterwards, they lose this regenerative potential. Previous studie...Background It has been widely observed that infants and young children can reossify large calvarial defects when they are younger than 2 years of age; afterwards, they lose this regenerative potential. Previous studies have implicated that the dura mater serves as a key regulator of calvarial regeneration. However, the molecular mechanism of calvarial reossification remains elusive. Methods In order to identify the proteins that may participate in this process, we performed a proteome-wide comparison of the protein expression levels of immature and mature dura using 2D electrophoresis and MALDI-TOF mass spectrometry. The Western blotting was used to verify the results of the 2D electrophoresis/MALDI-TOF mass spectrometry. Results Eleven proteins were found to express with significant differences in the immature and the mature dura. Among them, the emergence of vimentin, tropomyosin, 13-actin and y-actin were further confirmed by the Western blotting analysis. Conclusion The proteins and proteomic profiles provide a better understanding of the molecular mechanism of calvarial regeneration.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China （No, 30470722, 30771982, 30772356）, Beijing Natural Science Foundation （No. 7052021, 7062010）, and Science and Technology New Star Funds of Beijing （No. 2004B27, 2005A29）
文摘Background Familial hypercholesterolemia （FH）, caused by low density lipoprotein （LDL） receptor （LDL-R） gene mutations, is associated with increased risk of premature coronary heart disease. Until now, limited molecular data concerning FH are available in China. The present study described the clinical profiles and cell biological defects of a Chinese FH kindred with novel LDL-R gene mutation. Methods The patient＇s LDL-R gene coding region was sequenced. The patient＇s lymphocytes were isolated and the LDL-R expression, binding and up-take functions were observed by immunohistochemistry staining and flow cytometry detection. The patient＇s heart and the major large vessels were detected by vessel ultrasound examination and myocardial perfusion imaging （MPI）. Results The patient＇s LDL-R expression, LDL binding and up-take functions were significantly lower than normal control （39%, 63% and 76% respectively）. A novel homozygous 1439 C→T mutation of the LDL-R gene was detected in the patient and his family. ECG showed atypical angina pectoris. Echocardiogram showed stenosis of the coronary artery and calcification of the aortic valve and its root. Blood vessel ultrasound examination showed the thickness of large vessel intima, and the vessel lumen was narrowed by 71%. MPI showed ischemic changes. Conclusions The LDL-R synthesis dysfunction of FH patients leads to arterial stenosis and calcification, which are the major phenotype of the clinical disorder. The mutation of the LDL-R gene is determined. These data increase the mutational spectrum of FH in China.
文摘Background It has been widely observed that infants and young children can reossify large calvarial defects when they are younger than 2 years of age; afterwards, they lose this regenerative potential. Previous studies have implicated that the dura mater serves as a key regulator of calvarial regeneration. However, the molecular mechanism of calvarial reossification remains elusive. Methods In order to identify the proteins that may participate in this process, we performed a proteome-wide comparison of the protein expression levels of immature and mature dura using 2D electrophoresis and MALDI-TOF mass spectrometry. The Western blotting was used to verify the results of the 2D electrophoresis/MALDI-TOF mass spectrometry. Results Eleven proteins were found to express with significant differences in the immature and the mature dura. Among them, the emergence of vimentin, tropomyosin, 13-actin and y-actin were further confirmed by the Western blotting analysis. Conclusion The proteins and proteomic profiles provide a better understanding of the molecular mechanism of calvarial regeneration.
