Serum versus intrahepatic HCV RNA and liver histology
Serum versus intrahepatic HCV RNA and liver histology
复制标题
血清与肝内 HCV RNA 和肝脏组织学比较
作者：
V. Dries;P. Schirmacher;H. Dienes;G. Gerken;R. Bartenschlager
To the Editor: Vu et al. (HEPATOLOGY 2001;34:116-120) recently showed depletion of mitochondrial DNA in liver from 2 patients with Navajo neuropathy (NN) and postulated that the primary defect is in nuclear regulation of mitochondrial DNA copy number. In 1997, we proposed that liver disease in children with NN may result from MDR3 deficiency (HEPATOLOGY 26(suppl):369A). Northern analysis of RNA from the liver of an affected child revealed severe reduction in MDR3 messenger RNA (mRNA) abundance (Fig. 1A), as did reversetranscription polymerase chain reaction (RT-PCR) analysis of liver biopsy samples from 3 other affected children. mRNAs for other canalicular transporters, including MDR1 and MRP2, showed no difference from normal controls. The relation between reduced MDR3 expression and the neurologic symptoms of NN was unclear. However, Northern analysis indicated that MDR3 is expressed in multiple areas of human brain (Fig. 1B). Mdr2, which is the murine form of MDR3, is expressed in the developing brain of normal mice, but is not detected in the brain or liver of mdr2 / mice. These findings suggested that MDR3 dysfunction may also contribute to neurologic aspects of NN. To further assess whether MDR3 deficiency is a causative factor, we attempted to identify a mutation in the MDR3 gene that could account for reduced expression in NN. Although MDR3 message was severely depleted in the liver samples, a weak signal was evident by Northern and RTPCR analysis, indicating the presence of MDR3 mRNA. Full-length complementary DNA clones were assembled from RT-PCR products generated from a patient’s liver RNA. Sequence analysis of these clones failed to identify a mutationintheMDR3mRNA,however,wecouldnotexclude mutations in nontranscribed sequences. To determine whether mutations in MDR3 transcriptional regulatory sequences are associated with decreased mRNA levels, we obtained genomic DNA from 1 NN patient. Sequence was determined from 2.5 kb upstream of the transcriptional start site through exon 1, from the 28 MDR3 exons, and from 100 to 300 nucleotides flanking each exon. No mutations were identified in these regions when the sequence of the patient was compared with that of 64 unaffected controls. These data do not exclude MDR3 as a possible causative factor in NN. Reduced levels of MDR3 expression may result from mutations in the interior of introns, more distal regions of the promoter, or a cis-acting regulatory gene located elsewhere in the genome. Alternatively, selective reduction in MDR3 expression may be secondary to liver damage caused by the primary defect. The search goes on.
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DOI：
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发表时间：
1997-12
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
M. Paine;M. Khalighi;J. Fisher;D. Shen;K. Kunze;C. Marsh;J. Perkins;K. Thummel
通讯作者：
M. Paine;M. Khalighi;J. Fisher;D. Shen;K. Kunze;C. Marsh;J. Perkins;K. Thummel
影响因子：
15.9
作者：
Lown, KS;Bailey, DG;Watkins, PB
通讯作者：
Watkins, PB
影响因子：
10.8
作者：
Benet, LZ;Izumi, T;Wacher, VJ
通讯作者：
Wacher, VJ
改良 Caco-2 单层的咪达唑仑代谢：细胞外蛋白结合的影响。
DOI：
--
发表时间：
1999
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Fisher,JM;Wrighton,SA;Calamia,JC;Shen,DD;Kunze,KL;Thummel,KE
通讯作者：
Thummel,KE