Yuji Hoshino

Expressions of receptor gene for hepatocyte growth factor in kidney after unilateral nephrectomy and renal injury

The renal expressions of the receptor gene (c-met) for hepatocyte growth factor (HGF) were examined in unilateral nephrectomy (UNX), renal ischemia or folic acid administration. The levels of c-met mRNA were increased rapidly in all rat models at 6h after the operations. On the other hand, the expression of c-met mRNA in a kidney cell line (MDCK cells) was down-regulated for 8 h after HGF addition, indicating that c-met mRNA induction in rat models may be independent of the stimulated production of HGF. The stimulated expression of c-met in these models suggest that HGF may play an important role in renal hypertrophy after UNX and regeneration after ischemic or nephrotoxic injury.

Detection and analysis of replicating hepatitis C virus RNA in hepatocellular carcinoma tissues.

Although persistent hepatitis C virus infection is closely associated with the development of hepatocellular carcinoma, the nature of hepatitis C virus replication in the hepatocellular carcinoma tissue has not been fully characterized. To study this, carcinoma and non-carcinoma tissues were obtained from five patients with hepatocellular carcinoma. Total RNA was recovered from each tissue, and a portion of the envelope gene of replicating hepatitis C virus was amplified by minus-strand-specific reverse transcription and nested polymerase chain reaction. The amplified cDNA was examined by single strand conformation polymorphism analysis and sequencing. Hepatitis C virus replication was detected in both carcinoma and non-carcinoma tissues in four patients who were positive for serum hepatitis C virus markers. In one patient, a single species with identical envelope 2 genome was obtained from both carcinoma and non-carcinoma tissues. In the other three patients, the replicating hepatitis C virus existed as a mixture of 2-5 species with different but highly homologous (82-99%) envelope 2 genomes (quasispecies populations). The constitution of viral populations was different between carcinoma and non-carcinoma tissues. A total of ten sequences were recovered; four sequences were found in both tissues, two were found in carcinoma tissues, and four were found in non-carcinoma tissues. The difference in the constitution of quasispecies populations between carcinoma and non-carcinoma tissues confirms the unequivocal replication of hepatitis C virus in both tissues, and may imply the presence of different biological properties among hepatitis C virus with different sequences.

NORMAL HUMAN CHROMOSOME 5, ON WHICH A FAMILIAL ADENOMATOUS POLYPOSIS GENE IS LOCATED, HAS TUMOR SUPPRESSIVE ACTIVITY

The suppressive activity of normal human chromosome 5 was detected by means of the chromosomal transfer technique using DT cells as recipients. A hybrid clone, which exhibited reduced tumorigenicity, contained chromosomal regions such as 5pter-p15, q21 and q33-qter. Since a familial adenomatous polyposis gene has been reported to be located at 5q21-q22, the suppressive activity of chromosome 5 might be due to this gene.

Expression of the hepatocyte growth factor receptor in the regenerating rat liver

The c-met oncogene product is a cell-surface receptor, which ligand is believed to be the hepatocyte growth factor. We studied the expression of c-met oncogene in the regenerating rat liver after either partial hepatectomy or CCl4-induced liver injury. Northern blot analysis showed that after partial hepatectomy the transcripts of c-met decreased at 8 h, reached the minimum at 36 h, and returned to the steady level on the seventh day. In contrast with the hepatectomized liver, the transcripts of c-met increased after CCl4 treatment. These observations suggest that c-met transcription may be regulated differently depending on regeneration signals.

Two case reports of primary biliary cirrhosis associated with interstitial nephritis.

症例1は56歳男性. 1991年に原発性胆汁性肝硬変 (PBC) と診断されウルソデオキシコール酸 (UDCA) を内服し経過良好であった. 1994年頃より徐々に血清クレアチニン値が上昇した. 1997年に腎生検で間質性腎炎と診断されプレドニゾロン (PSL) 内服を開始した. PSL内服を開始しクレアチニン値は改善した. 症例2は55歳女性. 1994年PBCと診断されUDCA内服にて経過良好であった. 1996年頃より徐々に血清クレアチニン値が上昇し1997年腎生検で間質性腎炎と診断された. 尿細管性アシドーシスの合併も指摘された. PSL内服を開始して, クレアチニン値は改善した. PBCと間質性腎炎の合併は稀であり, 症例報告が3例みられるのみである. PBCの経過中に血清クレアチニンの軽度の上昇がみられた場合には間質性腎炎の合併を念頭におく必要があると考えられた.