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Biomedical subjects

M Ohto

Publications and source records attributed to M Ohto.

At least 73 records · Page 4Linked to original sources
PubMed1993

Hemodynamics of the left gastric vein in portal hypertension.

BACKGROUND: Esophageal varices reflect the hemodynamics of the left gastric vein, which can now be studied by Doppler ultrasonography. The purpose of this study was to elucidate the hemodynamic features of the left gastric vein in portal hypertension. METHODS: Flow direction and velocity in the left gastric vein were examined by the pulsed Doppler flowmeter in 53 healthy adults and 216 patients with liver cirrhosis. RESULTS: Flow direction was hepatopetal in all healthy controls, whereas it was hepatofugal in 72% of the patients with esophageal varices. In the early stage of mild esophageal varices, flow direction was still hepatopetal. However, in portal pressure > 250 mm H2O, hepatofugal flow was highly frequent (56 of 59 patients, 95%). Hepatofugal flow velocity in patients with varices was 8.5 +/- 2.5 cm/s in mild varices, 11.6 +/- 2.4 cm/s in intermediate varices, and 13.8 +/- 3.4 cm/s in marked varices. Variceal bleeding was frequent in patients with a flow velocity > 15 cm/s (7 of 14 patients, 50%). Flow velocity in the left gastric vein increased after ingestion of glucose in 43 of 56 patients with esophageal varices. CONCLUSIONS: In portal hypertension, as the size of varices enlarged, hepatofugal blood flow in the left gastric vein increased in parallel. High flow velocity in the left gastric vein was strongly associated with variceal bleeding. Increase of blood flow after ingestion of glucose suggests postprandial increase in variceal flow.

Administration, Oral↗
PubMed1993

Precore mutations and core clustering mutations in chronic hepatitis B virus infection.

BACKGROUND: Mutant hepatitis B virus is often associated with severe liver damage. The purpose of this study is to elucidate the relationship between mutations in hepatitis B precore/core gene and the severity of liver damage. METHODS: The hepatitis B precore/core gene from 20 patients with chronic hepatitis B virus infection was studied by polymerase chain reaction and direct sequencing. RESULTS: Missense mutations in the core gene were only found in patients with chronic active hepatitis. Three mutation clustering regions of core gene, codons 48-60, 84-101, and 147-155, had higher substitution rates than other regions. All patients with chronic active hepatitis had missense mutation(s) either in codons 84-101 or in codons 48-60. There was a trend of increasing substitutions in the precore/core gene from e antigen-positive asymptomatic carriers to e antibody-positive patients with chronic active hepatitis. CONCLUSIONS: These data suggest that (1) severe liver damage in chronic hepatitis B virus infection is related to the clustering missense mutations in codons 48-60 and 84-101 of core gene and that (2) the emergence of precore stop codon mutation and missense mutations around the carboxy-terminal processing site of precore/core protein (codons 147-155) may be the adaptive mechanisms of hepatitis B virus to decrease production and secretion of viral protein and retain the viral persistence.

Adult↗
PubMed1993

The effect of interferon alpha and prednisolone on the serum concentrations of the aminoterminal domain of procollagen type III(PIIIP) and type IV (7-S collagen) in patients with chronic hepatitis B.

Since interferons are reported to inhibit collagen synthesis in vivo and in vitro, they are possible anti-fibrogenic drugs. However, little is known about the effect of interferons on connective tissue metabolism in liver disease. To investigate the effect, serum concentrations of the aminoterminal domain of procollagen type III and type IV (7-S collagen) were measured in 16 patients with chronic hepatitis B during alpha interferon treatment. The levels were also determined during prednisolone withdrawal treatment to investigate the effect on hepatic collagen turnover. In patients with chronic hepatitis B, the serum levels of both markers were significantly elevated before any treatment (procollagen type III: 1.10 +/- 0.39 U/ml, 7-S collagen: 6.69 +/- 3.71 ng/ml) compared with levels in 41 healthy volunteers (pro-collagen type III: 0.53 +/- 0.13 U/ml, P < 0.001; 7-S collagen: 4.72 +/- 0.57 ng/ml, P < 0.001). Both levels were even more elevated during interferon therapy (procollagen type III: 1.36 +/- 0.58 U/ml, P < 0.05; 7-S collagen: 8.77 +/- 4.68 ng/ml, P < 0.01). On the other hand, serum procollagen type III and 7-S collagen levels were both decreased during prednisolone treatment (procollagen type III: 0.62 +/- 0.13 U/ml, P < 0.001; 7-S collagen: 4.66 +/- 1.69 ng/ml, P < 0.01). These preliminary data suggest that interferon alpha enhanced, but prednisolone inhibited the turnover of procollagen type III and IV in the liver. Further study is required to interpret this observation in relation to anti-fibrotic therapy.

Adolescent↗
PubMed1993

Protective effects of FUT-175 on acute massive hepatic necrosis induced in mice following endotoxin injection and immunization with liver proteins.

Experimental autoimmune hepatitis was induced in C57BL/6 mice by immunization with syngeneic liver protein and adjuvant. Hepatitis was characterized by marked cellular infiltrates, but hepatic necrosis was mild to moderate. A small dose of endotoxin (25 micrograms/mouse) produced lethal hepatitis with elevation of serum transaminase levels in these mice. The endotoxin-induced reactions were completely inhibited by i.p. administration of FUT-175 (5 mg/kg), a synthetic protease inhibitor, 1 h before the endotoxin injection. In vitro experiments showed that two-thirds of the inflammatory infiltrates were monocyte/macrophages. Cytotoxicity against syngeneic hepatocytes was significantly increased by the addition of endotoxin (25 micrograms/ml), but the same dose of endotoxin alone had no effect on the viability of hepatocytes. The endotoxin-induced increase in cytotoxicity was prominent in the glass-dish adherent (monocyte/macrophage enriched) fraction and was also demonstrated after depletion of T-cells. However, elevated cytotoxicity did not occur when FUT-175 (> 1 x 10(-7) M) was present throughout the assay period. These results seem to indicate that the hepatotoxic effects of endotoxin are mediated, at least in part, by monocytes or macrophages infiltrating the liver following immunization of liver proteins. Our results also suggest that FUT-175 has protective effects against endotoxin-induced hepatotoxic reactions.

Acute Disease↗
PubMed1993

Expression of HCV E2/NS1 protein as a fusion protein with maltose binding protein: detection of anti-E2/NS1 antibody in chronic liver disease.

The presence of anti-E2 antibody was investigated in the serum samples of 46 patients with liver disease, who were positive for hepatitis C virus-RNA, and in five subjects HCV-RNA-negative acting as controls. Antibody to E2/NS1 protein was found in seven of 46 (15%) of the patients with liver disease but in none of the control subjects. In one patient who was treated successfully with interferon, the levels of anti-E2 gradually decreased and then finally disappeared after treatment. This suggests that the E2/NS1 protein may play a role in active viral replication.

ATP-Binding Cassette Transporters↗
PubMed1993

Mutations in core nucleotide sequence of hepatitis B virus correlate with fulminant and severe hepatitis.

Infection with hepatitis B virus leads to a wide spectrum of liver injury, including self-limited acute hepatitis, fulminant hepatitis, and chronic hepatitis with progression to cirrhosis or acute exacerbation to liver failure, as well as an asymptomatic chronic carrier state. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes. To investigate the reason why the extreme immunological attack occurred in fulminant hepatitis and severe exacerbation patients, the entire precore and core region of hepatitis B virus DNA was sequenced in 24 subjects (5 fulminant, 10 severe fatal exacerbation, and 9 self-limited acute hepatitis patients). No significant change in the nucleotide sequence and deduced amino acid residue was noted in the nine self-limited acute hepatitis patients. In contrast, clustering changes in a small segment of 16 amino acids (codon 84-99 from the start of the core gene) in all seven adr subtype infected fulminant and severe exacerbation patients was found. A different segment with clustering substitutions (codon 48-60) was also found in seven of eight adw subtype infected fulminant and severe exacerbation patients. Of the 15 patients, 2 lacked precore stop mutation which was previously reported to be associated with fulminant hepatitis. These data suggest that these core regions with mutations may play an important role in the pathogenesis of hepatitis B viral disease, and such mutations are related to severe liver damage.

Adult↗
PubMed1993

[Treatment of common bile duct stones by peroral cholangioscopy].

Endoscopic papillotomy (EPT) has become a popular form of treatment in managing common bile duct stones. But it may fail in difficult cases such as large stones of over 20 mm, confluence stones, and impacted stones. Over the past 5 years, our success rate in clearing the bile duct by conventional endoscopic techniques (mechanical lithotripsy) was about 90 per cent. Recently, we have performed electrohydraulic lithotripsy or laser lithotripsy with peroral cholangioscopy in these difficult cases. Complete clearance of the duct was obtained in all 23 patients who underwent peroral cholangioscopic lithotripsy. No complication occurred. In conclusion, peroral endoscopic treatment of common bile duct stones should be safe and effective.

Aged↗
PubMed1993

[Percutaneous ethanol injection (PEI) for small hepatocellular carcinoma].

Percutaneous ethanol injection (PEI) was applied to 162 lesions in 133 patients with hepatocellular carcinomas (HCC) 3 cm or less in diameter (small HCC) between Aug. 1983 and Apr. 1992. Histological findings in resected specimen for which PEI had previously been performed before surgery showed that PEI could completely necrotize an HCC of 32 mm in diameter. The antitumoral effect by PEI could correctly be evaluated by enhanced CT. The 1-, 3-, 5- and 7-year survival rates after PEI calculated by the Kaplan-Meier method were 95.9%, 60.5%, 36.9% and 21.7%, respectively. The survival rate of post-PEI patients with I or II grade in clinical stage was better than that of those with III. Recurrence occurred in hepatic areas different from the original lesion in 27.8% in one year and 63.6% in three years after PEI, rates quite similar to those of recurrence after surgical resection for HCCs of 3 cm or less in diameter. For such recurrence, PEI alone was then repeated in half of the 76 patients. Complications caused by PEI were not serious and did not necessitate intensive care. Because of its anti-tumor therapeutic effect and minimal damage to the liver, PEI might be considered a viable alternative to surgery for most patients with small HCC.

Carcinoma, Hepatocellular↗
PubMed1993

[Usefulness of percutaneous biopsy under sonographic control and histological examination in the early diagnosis of hepatocellular carcinoma].

We evaluated the usefulness of percutaneous biopsy under sonographic control and histological examination in the early diagnosis of hepatocellular carcinoma (HCC) in comparison with CT and angiography. 121 patients in whom hepatic nodules 3cm or smaller in size were found by ultrasound as suspected HCC underwent percutaneous biopsy, CT and angiography. 118 patients were finally diagnosed as HCC. Correct diagnosis of HCC was obtained by each modality in relation to tumor size as follows: 87.3% by histological examination, 55.1% by CT, 52.5% by angiography. However, the diagnostic capability of these modalities for HCC 1.5cm or smaller in size was as follows: 88.5% by histological examination, 34.6% by CT, and 23.1% by angiography. Cytology using a biopsy specimen was performed in 26 patients and it showed a positivity of 61.5%. In conclusion, for a definitive diagnosis of small HCC 1.5cm or less in size, the current imaging modalities have some limitations. On the other hand, percutaneous biopsy and histological examination are the most reliable and indispensable for making a definite diagnosis of small HCC.

Adult↗
PubMed1993

Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction: increase of the virus in advanced liver disease.

We developed a quantitative method of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction. With this method, 36 patients with type C chronic liver disease were analyzed for the copy number of circulating hepatitis C virus in 50 microliters of serum. The amounts of hepatitis C virus RNA ranged from 10(1) to 10(7) copies in the 36 patients. The average amount of hepatitis C virus RNA was 10(3.3 +/- 2.2) copies in 12 patients with chronic persistent hepatitis, 10(5.7 +/- 1.6) copies in 12 patients with chronic active hepatitis and 10(6.0 +/- 1.6) copies in 12 patients with cirrhosis (including 4 patients with hepatocellular carcinoma). The amount of hepatitis C virus RNA in serum was significantly less in patients with chronic persistent hepatitis than in patients with chronic active hepatitis or cirrhosis (p < 0.01), and it tended to increase according to the progression of histopathological changes of the liver. Furthermore, it was revealed that the amount of hepatitis C virus RNA became exponentially larger as the term from infection became longer. Quantification of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction may have many applications for the study of clinical features of hepatitis C virus infection.

Adult↗
PubMed1993

Prospective assessment of donor blood screening for antibody to hepatitis C virus and high-titer antibody to HBcAg as a means of preventing posttransfusion hepatitis.

Since December 1989, the Japan Red Cross Blood Bureau has screened blood donors for hepatitis C virus antibody on the basis of enzyme-linked immunosorbent assay and high titers of antibody to HBc antigen. To elucidate the effectiveness of the new screening tests in preventing posttransfusion hepatitis, the incidence of posttransfusion hepatitis after the introduction of the new tests (December 1989 to December 1990) was compared with the incidence before their introduction (January 1982 to December 1988). The incidence of posttransfusion hepatitis was 9.8% (219 of 2240), with a mean transfusion volume of 10.2 units, before the screening and 3.7% (12 of 326), with a mean transfusion volume of 14.7 units, after the introduction of the new tests. Statistical analysis revealed a significant decrease of incidence of posttransfusion non-A, non-B hepatitis after the introduction of the new tests (X2 = 10.9, p < 0.01). Posttransfusion hepatitis B occurred in 3 of 2,240 recipients (0.13%) before the introduction of HBc antibody testing. No cases of posttransfusion B viral hepatitis developed after the introduction of the new tests. Hepatitis C virus antibody status was investigated in 7 of 12 posttransfusion hepatitis patients who contracted the disease after the new screening tests were initiated. Hepatitis C virus antibody seroconversion occurred in three of the seven cases (43%), as detected on first- and second-generation hepatitis C virus antibody assays and reverse-transcription polymerase chain reaction.

Aged↗
PubMed1993

[ADH 2, 3 and ALDH 2 gene frequency in Japanese alcoholics].

To elucidate genetic susceptibility to alcoholic liver injury (ALD), polymerase chain reaction (PCR) method assay was developed to detect point mutations in each gene and gene frequency in various liver diseases was studied. It was shown previously that ALDH2(1) gene was more frequently found in patients with ALD (confirmed in this study), probably because they are able to consume too much alcohol (non-flushing type). This study revealed that, in addition to this ALDH heterogeneity, ADH heterogeneity may correlate with the severity of alcoholic liver injury, especially in those was low ADH activity and tend to have severe damage.

Alcohol Dehydrogenase↗
PubMed1992

Detection of antibody to hepatitis C E2/NS1 protein in patients with type C hepatitis.

Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein. Approximately 80 kDa protein was obtained containing 38 kDa E2/NS1 protein. The antibody to this protein was detectable in the same serum from which the sequence was amplified. It was also detectable in none of 7 acute hepatitis, in 2 of 12 chronic persistent hepatitis, in 3 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was detectable in none of 10 normal subjects. In 3 cases who were positive for the antibody before the interferon treatment, it became undetectable after the treatment. Thus, it seems that the antibody is not a neutralizing antibody and is related to active viral replication.

Base Sequence↗
PubMed1992

Determination of nucleotide sequence of active site for catalytic properties of ADH3 genes.

Alcohol dehydrogenase genes show polymorphism. gamma subunits, which are encoded by ADH3 genes, have two subtypes according to the single base substitution of codon 271 and 349. This mutation of codon 271 directly determines subtypes with different catalytic properties. However, there has been no simple technique to detect nucleotide changes at codon 271. Specific amplification of nucleotides around codon 271 was difficult because of homologous nucleotide sequences around the region among 3 ADH genes (ADH1, 2 and 3). We have developed a method to amplify the ADH3 gene alone with a modification on 3'-end of primer by polymerase chain reaction. Approximately 200 nucleotides including codon 271 of ADH3 gene were sequenced, and genotypes of ADH3 gene were determined in 30 Japanese individuals. This method may facilitate the studies on racial differences of genotypes and involvement of ADH genes in patients with alcoholic liver disease.

Alcohol Dehydrogenase↗
PubMed1992

High incidence of ras gene mutation in intrahepatic cholangiocarcinoma.

The DNA sequences around codons 12, 13, and 61 of the ras gene were analyzed by polymerase chain reaction and direct sequencing in 18 intrahepatic cholangiocarcinomas. The ras gene mutations were found in 9 of 18 (50%): 6 in K-ras codon 12, 1 in K-ras codon 13, 1 in K-ras codon 61, and 1 in N-ras codon 12. The incidence of mutations was higher in the hilar type of intrahepatic cholangiocarcinomas, especially when these tumors were large. The incidence and spectrum of the mutations were almost the same as those reported in colon cancers, possibly indicating similar etiologic agent(s) in the carcinogenesis of both cancers.

Adenocarcinoma↗
PubMed1992

Nucleotide sequence of prothrombin gene in abnormal prothrombin-producing hepatocellular carcinoma cell lines.

A protein induced by vitamin K absence or antagonist II, PIVKA-II is synthesized in the liver and possesses a structure similar to prothrombin except that ten glutamic acid residues in amino-terminal Gla domain are not completely gamma-carboxylated and are functionally inactive. This protein can be detected in the plasma of patients with hepatocellular carcinoma (HCC) and used as a new tumor marker. To analyze the mechanism of PIVKA-II production in HCC tissue, the prothrombin gene of PIVKA-II-secreting HCC cell lines was sequenced to detect the mutation in the Gla domain and carboxylase recognition site of leader sequence located on exons I and II that may cause the inhibition of carboxylation. Exons I and II and donor and acceptor site of intron I of the prothrombin gene in two HCC cell lines, PLC/PRF/5 and huH-2, were analyzed by polymerase chain reaction (PCR), and the product was sequenced directly. In addition, RNA samples of these cell lines were used for complementary DNA synthesis, followed by PCR and sequencing. The nucleotide sequences of the Gla domain in both HCC cell lines were conserved. One nucleotide change was detected at nt.554 (adenine to guanine), but this did not influence the amino acid sequence. Splicing sites between exons I and II, the leader sequence of the precursor prothrombin, and protease target sites also were conserved as the reported prothrombin gene, and mutations reported for other des-gamma-carboxy coagulation factors were not detected. These results also were confirmed by DNA analysis of seven human fresh-frozen samples (three PIVKA-II-positive HCC samples and four control specimens). The mechanism of PIVKA-II production in HCC is still unclear, but it is not caused by mutation in the prothrombin gene.

Amino Acid Sequence↗
PubMed1992

Non-A, non-B chronic hepatitis is chronic hepatitis C: a sensitive assay for detection of hepatitis C virus RNA in the liver.

To study the role of hepatitis C virus in non-A, non-B chronic hepatitis, 49 liver biopsy samples from 40 patients with non-A, non-B chronic hepatitis and 9 control patients were analyzed by complementary DNA/polymerase chain reaction. Two segments of the HCV genome, one in the nonstructural region and the other in the noncoding region, were amplified by two sets of primer pairs. With use of the nonstructural region primers, hepatitis C virus RNA was detected in 24 (60%) of 40 patients with non-A, non-B chronic hepatitis. Of these 40 patients, RNA was detected in 19 (70%) of 27 patients positive for antibody to hepatitis C virus and in 5 (38%) of 13 patients negative for antibody to hepatitis C virus. However, with the noncoding region primers, hepatitis C virus RNA was detected in 38 (95%) of 40 patients with non-A, non-B chronic hepatitis. Of these patients, the RNA was detected in 26 (96%) of 27 patients positive for antibody to hepatitis C virus and also in 12 (92%) of 13 patients positive for antibody to hepatitis C virus. Hepatitis C virus RNA was not detected in any of the control patients. Sequence analysis showed homology between our samples and the prototype to be only 66% to 77% in the nonstructural region but 99% to 100% in the noncoding region. We conclude that almost all patients with non-A, non-B chronic hepatitis in Japan are currently infected with hepatitis C virus, regardless of the presence or absence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗