[The clinical utility of the detection of hepatitis C virus genome by polymerase chain reaction].
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Genes, Viral↗
Biomedical subjects
M Ohto
Publications and source records attributed to M Ohto.
[Cases of chronic hepatitis which showed clear changes of serum levels of 7S-collagen in response to steroid and interferon therapy].
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Aged↗
Ultrasonography of cervical lymphadenopathy in a patient with Kikuchi's disease.
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Adult↗
Analysis of ras gene mutations in biliary and pancreatic tumors by polymerase chain reaction and direct sequencing.
Ras gene is one of the oncogenes most commonly detected in human cancers and consists of three families (H-ras, K-ras, N-ras) that are converted to active oncogenes by point mutations occurring in codon 12, 13, or 61. The authors analyzed mutations of these codons in 12 extrahepatic bile duct carcinomas, nine gallbladder carcinomas, and 20 pancreatic tumors (18 pancreatic adenocarcinomas and two islet cell tumors) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Point mutations at K-ras codon 12 were found in all of 18 pancreatic adenocarcinomas and in one bile duct carcinoma, but there were no mutations in the remaining 11 bile duct carcinomas, in all of 9 gallbladder carcinomas, or in two islet cell tumors. A very high incidence of ras gene mutations may be used clinically for the diagnosis of debatable cases of pancreatic adenocarcinoma.
Adenoma, Islet Cell↗
Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing.
The ras gene is one of the oncogenes most commonly detected in human cancers, and it consists of three families (H-ras, K-ras, N-ras). These genes are converted to active oncogenes by point mutations occurring in either codon 12, 13, or 61. We analyzed mutations of these codons in 23 primary hepatic malignant tumors (12 hepatocellular carcinomas, nine cholangiocarcinomas, and two hepatoblastomas) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Of 23 hepatic malignant tumors, point mutations at K-ras codon 12 or K-ras codon 61 were found in six of nine cholangiocarcinomas. In contrast, there were no point mutations in any of 12 hepatocellular carcinomas or two hepatoblastomas around codon 12, 13, or 61 of the ras genes. These observations suggest that ras gene mutations are not related to pathogenesis of hepatocellular carcinoma, but play an important role in pathogenesis of cholangiocarcinoma.
Adenoma, Bile Duct↗
Extrahepatic replication of duck hepatitis B virus: more than expected.
Replication of duck hepatitis B virus in extrahepatic tissue such as pancreas, kidney and spleen has been well documented. To assess whether there is more widespread extrahepatic virus replication, we assayed brain, heart, lung, thymus, pancreas, kidney, spleen and intestine of 1- to 16-wk-old ducklings for the presence of duck hepatitis B virus DNA and mRNA by blotting and in situ methods. Replicative intermediates and single-stranded duck hepatitis B virus DNA and RNA transcripts were detected in the brain, lung, heart, intestine, kidney, pancreas and spleen. In situ hybridization showed evidence of viral replication in the lung epithelium, germinal center of spleen, acinar cell of pancreas and tubular epithelium of kidney. These data suggest that extrahepatic duck hepatitis B virus replication is more widespread than previously thought. It is yet to be determined whether widespread extrahepatic replication is unique to duck hepatitis B virus infection or is a common feature of other mammalian hepatitis B-like viruses.
Animals↗
Histological features and clinical course of large regenerative nodules: evaluation of their precancerous potentiality.
Seventeen patients with cirrhosis and histologically defined, ultrasonically detected, large regenerative nodules of the liver were followed without treatment for more than 1 yr (range = 13 to 51 mo). During the follow-up period, none of the nodules were demonstrated sonographically to have enlarged. Computed tomography and/or hepatic angiography were also performed in 14 patients, but there was no evidence of malignant transformation in these lesions. None of the 17 patients showed acute elevation of serum alpha-fetoprotein levels. Furthermore, four nodules became undetectable by these imaging procedures. Follow-up biopsy performed in seven patients revealed no significant histological changes from the first biopsy sample. However, HCCs developed apart from these large regenerative nodules in four patients. These HCCs suddenly appeared and did not seem to have been derived from preexisting large regenerative nodules. From these observations, it was not possible to regard a large regenerative nodule having no cytological atypia as a high-potential premalignant lesion. Their precancerous potentiality needs to be compared with that of ordinary pseudolobules.
Angiography↗
Relative frequencies of portosystemic pathways and renal shunt formation through the "posterior" gastric vein: portographic study in 460 patients.
Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the "posterior gastric" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%).
Collateral Circulation↗
Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets. A preliminary report.
An in vitro assessment of susceptibility to malotilate was made with peripheral blood mononuclear cells (PBMCs) as targets. PBMCs were incubated with malotilate in the presence or absence of the NADPH generating system and hepatic microsomes. Malotilate cytotoxicity to PBMCs, assessed by trypan blue dye exclusion and lactate dehydrogenase (LDH) release into the culture media, was found to be markedly increased by the addition of the NADPH generating system, indicating that metabolites play a significant role in toxicity. Once the significant role of malotilate metabolites in cytotoxicity was established, we applied this system to patients with suspected malotilate-induced liver injury. It was demonstrated that cytotoxicity was greater in PBMCs which were obtained from patients with chronic active hepatitis with a parallel malotilate-induced liver injury than in those from two different control groups; normal volunteers and patients with chronic active hepatitis who had had long-term malotilate treatment without any adverse reactions. This in vitro system seems to be of value in predicting potential malotilate toxicity in subjects who might be susceptible to this drug.
Adult↗
Heterogeneity and evolution rates of delta virus RNA sequences.
To investigate the geographical divergence of delta virus RNA sequences, 868 nucleotides (nt), including the delta antigen-coding region, were determined in isolates from two Japanese patients, M and S, by polymerase chain reaction and direct sequencing and compared with three previously reported nucleotide sequences. The sequence obtained for hepatitis delta virus RNA from patient M was approximately 92% identical to sequences previously obtained for two other strains of hepatitis delta virus, whereas the sequence of hepatitis delta virus RNA obtained from patient S was approximately 81% identical to the previously sequenced strains. This suggests that delta agent in Japan has a heterogeneous origin and the delta virus RNA sequence from Japanese patient S is the most divergent delta virus isolate yet analyzed. To study the evolution rate of delta virus RNA, viral isolates obtained 3 and 4 years apart from each of two patients were also sequenced. It was estimated that the substitution rate of viral RNA was 0.57 x 10(-3) nt per site per year in patient M and 0.64 x 10(-3) nt per site per year in patient S for the delta antigen gene.
Amino Acid Sequence↗
Detection of hepatitis C virus ribonucleic acid in the serum by amplification with polymerase chain reaction.
Hepatitis C virus (HCV) RNA was detected in the sera of patients with non-A, non-B chronic liver disease by polymerase chain reaction (PCR). RNA was extracted from the serum, reverse transcribed to cDNA, and amplified by PCR. With this method, 30 patients with non-A, non-B chronic liver disease and 10 healthy subjects were tested. HCV RNA was detected in 13 of 16 (81%) anti-HCV-positive patients and also in 7 of 14 (50%) anti-HCV-negative patients, but in none of 10 anti-HCV-negative healthy subjects. Specificity of this method was confirmed by direct sequencing of amplified cDNA segment. The nucleotide sequences (37 nucleotides) obtained from 15 patients showed only 68-78% homology compared with the prototype HCV nucleotide sequence. In addition, of 15 nucleotide sequences, there were 12 different types. But the translated amino acid sequences (12 amino acids) showed 83-100% homology compared with the prototype HCV amino acid sequence. These data suggest the majority of anti-HCV-positive patients are carriers of HCV. But to detect all the viremic patients, the anti-HCV antibody testing may be insufficient. Direct detection of HCV RNA may be useful in the study of virus replication and its association with various liver diseases.
Adolescent↗
[Long-term treatment for non-A, non-B chronic hepatitis--effects on hepatitis C virus (HCV)].
We have treated 16 patients with chronic non-A, non-B hepatitis with short term (7-13 weeks) and long term (1 year) interferon. Sustained effect (normalization) of treatment was noted in all by long term treatment, where 7 of 8 with short term treatment showed flare-ups of transaminase after the therapy. In addition, negative turn of anti-HCV antibody was noted in 2 of 5 patients with long term treatment, whereas such change was noted in none of 6 anti-HCV antibody positive patients treated with short term treatment. These data suggest that long term interferon therapy may change natural course of chronic non-A, non-B hepatitis caused by HCV.
Adult↗
[A combination treatment of transcatheter arterial embolization (TAE) and irradiation for hepatocellular carcinoma (HCC)--evaluation for therapeutic efficacy in comparison with TAE or irradiation alone].
Therapeutic effects of a combination therapy (TAE and irradiation) and a radiation therapy alone were evaluated comparatively in 54 patients with HCCs. Twenty eight patients of them underwent external X-irradiation with a linear accelerator after TAE and the remaining twenty six did irradiation alone. The incidence of partial response was 82.1% in the combination therapy and 69.2% in the radiation therapy. The cumulative rates of survival in the combination therapy were 70.8% (1-year), 37.1% (3-year), and 27.9% (5-year), which were higher than those in the radiation therapy. The cumulative rates of recurrence in the former were lower than those in the latter. The prognoses after the both treatments were poor in the patients with advanced liver cirrhosis (Child C). In the patients with HCCs smaller than 5 cm in diameter or accompanied by portal vein thrombi, the combination therapy was superior to TAE alone in the cumulative rates of survival. It is considered from the above results that the combination therapy is useful in the patients with HCCs when properly selected.
Carcinoma, Hepatocellular↗
[Relationship between ultrasound-findings of low-echoic nodule of hepatic parenchyma in liver cirrhosis and development of hepatocellular carcinoma].
We investigated development of hepatocellular carcinoma (HCC) in 90 patients with liver cirrhosis by follow up study for a period from 6 months to three and half years, making special reference to ultrasound-findings of the parenchyma of the liver. Liver cirrhosis was classified into four types and two, non-nodular and nodular, groups according to low-echoic nodules distributed in the parenchyma. The development of HCC was higher at the rate of incidence in patients of the nodular group than those of the non-nodular. It was more closely related with the male in patients of the non-nodular group, and both the old age and the advanced hepatic injury in those of the nodular group. A rise of the level of serum AFP during a period of the follow up was not observed in relation to the development of HCC and seemed to be ineffective for detection of carcinoma small sized. The echo-types of the parenchyma in liver cirrhosis were most significantly correlated with the development of HCC in comparison with the other etiologic factors.
Adult↗
[Detection of ras gene mutations of primary hepatic malignant tumors by polymerase chain reaction and direct sequencing method].
Ras genes are converted to active oncogenes by point mutations occurring in either codon 12, 13 or 61. We used polymerase chain reaction and direct sequence method for the analysis of these mutations. We examined 13 hepatocellular carcinomas, 8 cholangiocarcinomas, 2 hepatoblastomas and 1 biliary cystadenocarcinoma. Of these tumors, ras gene mutations were detected solely in cholangiocarcinomas. Cholangiocarcinoma showed a high incidence of K-ras gene mutation. Among 8 patients with cholangiocarcinoma, the mutation was detected at codon 12 in 4 and at codon 61 in 1. The incidence of K-ras gene mutation was especially high in the hilar type of cholangiocarcinoma as compared with the peripheral type.
Adenoma, Bile Duct↗
[Utility of percutaneous biliary drainage in patients with hepatic hilar carcinoma in reference to prognosis and associated complication].
We investigated prognosis in 48 patients with hepatic hilar carcinoma (35 treated with percutaneous biliary drainage (PBD) and 13 without PBD) and complication associated with PBD. Survival rate in 20 patients who had no cholangitis within 1 month after PBD was significantly superior to that in 15 patients with cholangitis. The former was 51.9% at 6 months and 13.0% at 1 year. We thought that this result would be helpful in estimating prognosis in patients with hepatic hilar carcinoma treated with combined therapy. Cholangitis within 1 month after PBD was caused from inadequate drainage for separated intrahepatic bile ducts, ERC before PBD and dislodgement of drainage catheter. Survival rate in patients with PBD not accompanied by cholangitis in 1 month after was superior to that in those without PBD. So we thought that PBD could improve prognosis in patients with hepatic hilar carcinoma if they had no cholangitis within 1 month after PBD.
Aged↗
[Diagnostic capability and clinical usefulness of percutaneous histological biopsy of the pancreas under control on ultrasound image using 21 gauge needle].
We evaluated diagnostic capability and clinical usefulness of histological diagnosis of the pancreas by percutaneous biopsy controlled on ultrasound image. Thirty seven patients with pancreas carcinoma and 11 with chronic pancreatitis underwent the procedure using 21 guage-Sonopsy C1 needle (Hakko co. Ltd.). Specimens of the tissue obtained were adequate for histological interpretation in 95.8% of all the 48 patients. The histological judgement referring to the nature of the lesion corresponded in 91.3% with the final diagnosis established surgical exploration, autopsy or long follow up more than one year. In cases of pancreas carcinoma with a successful procedure of the biopsy, histological type of carcinoma was confirmed in 91.4% of the tumors. It proved accordant pathologically with the conclusion based on the resected tumors in 5 of 8 patients operated on after the biopsy. Chronic pancreatitis was histologically diagnosed in 9 of the 11 patients with the biopsy. A confident diagnosis could not be obtained by imaging modalities including ultrasound, X-ray CT, ERCP and angiography in 7 of 37 patients with pancreas carcinoma and 3 of 11 with chronic pancreatitis. Biopsy by this method was so useful as to obtain the correct diagnosis in all these cases but one. Abdominal pain happened most frequently as a adverse effect during the procedure, but disappeared soon after that. There were no serious complications requiring intensive care. In conclusion, percutaneous histological biopsy controlled on ultrasound image may be recommended as a reliable method for making a definite diagnosis providing more valuable information than cytological biopsy, when diagnostic imaging modalities are unsuccessful in elucidating pathology of the pancreas.
Adult↗
[Long-term follow-up results in nonoperated patients with intrahepatic and predominant intrahepatic type of hepatolithiasis].
In order to clarify therapeutic principles of hepatolithiasis associated with a variety of pathological conditions, we studied follow-up results in a term of 5 years after diagnosis in 29 nonoperated patients with intrahepatic gallstones. The patients including 14 males and 15 females underwent direct cholangiography for making diagnosis of the disease consisting of the intrahepatic type (I) and the predominant intrahepatic (IE). Out of the patients, 21 had good results in the follow-up and no one died from the disease or cholangiocarcinoma incidentally occurred. The follow-up results were closely related with the distribution and the location of gallstones in the liver and the grade of severity in clinical symptoms at the diagnosis. The unilateral lober type of the stone distribution had better follow-up results than the bilateral (P less than 0.01), and the peripheral intrahepatic bile duct type of the stone location did better follow-up results than the major (P less than 0.01). The pathological state of mild clinical symptoms showed better follow-up results than that of severe ones (P less than 0.05). The removal of coexisted extrahepatic bile duct stones by endoscopic papillotomy was effective for improving clinical symptoms. The conservative treatment in hepatolithiasis with the type I or IE was generally good in the follow-up results. The follow-up results were various, depending on the pathological conditions at the diagnosis. Accordingly, the treatment of hepatolithiasis must be selected in consideration of pathological conditions.
Adolescent↗