Familial clustering of HCV.
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Chronic Disease↗
Biomedical subjects
S Nishiguchi
Publications and source records attributed to S Nishiguchi.
Detection of hepatitis C virus antibody in the absence of viral RNA in patients with autoimmune hepatitis.
OBJECTIVE: To determine whether laboratory findings showing antibodies to hepatitis C virus (HCV) in patients with autoimmune hepatitis represent false-positive results and to identify possible explanations for true-positive results in these patients. DESIGN: Cross-sectional. SETTING: University-based hospital. PATIENTS: Fifty-two patients with non-A, non-B chronic hepatitis as a control group and 26 patients with classic chronic active autoimmune hepatitis. MEASUREMENTS: Comparison of the results of five kinds of assays of HCV antibodies and HCV RNA. MAIN RESULTS: Of 52 patients with non-A, non-B chronic hepatitis, HCV antibodies (anti-HCV) were detected in 42 patients (81%; 95% CI, 67% to 90%) by a first-generation enzyme-linked immunosorbent assay (ELISA-I), in 39 patients (75%) by Sp42 ELISA, in 37 patients (71%) by RIA-I, in 49 patients (94%) by ELISA-II, and in 48 patients (92%) by RIBA-II. We found HCV RNA in 47 patients (90%; CI, 79% to 97%). Of the 26 patients with autoimmune hepatitis, anti-HCV were detected in 23 patients (88%; CI, 70% to 98%) by ELISA-I, in 12 (46%) by both RIA-I and Sp42 ELISA, in 20 (77%) by ELISA-II, and in 9 (35%) by RIBA-II. However, HCV RNA was found in only five of these patients (19%; CI, 7% to 39%). None of our patients, including controls, had antibodies to superoxide dismutase. Of the 21 patients who had autoimmune hepatitis that was completely responsive to steroid therapy, 18 had anti-HCV by ELISA-I, but 13 of these patients had negative results by RIBA-II, and only two patients had HCV RNA. Of the five patients who did not respond to steroid treatment, all had anti-HCV by ELISA-I, four had negative results by RIBA-II, and three had HCV RNA. CONCLUSIONS: Testing for HCV antibodies in patients with autoimmune hepatitis frequently elicits positive results when the ELISA-I or ELISA-II tests are used. Most of these appear to represent false-positive results because HCV RNA is usually absent from the serum. Such false positivity may result from previous infection with HCV or from cross-reaction of an epitope of HCV. Other patients with apparent autoimmune hepatitis who fail to respond to corticosteroid therapy may actually have chronic hepatitis C (or other non-A, non-B hepatitis) infection.
Adult↗
Transmission of hepatitis C virus from mothers with chronic hepatitis C without human immunodeficiency virus.
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False Positive Reactions↗
Reduction by interferon-alpha of levels of c-myc protein and DNA synthesis in a human hepatoma cell line mediated by inhibition of putrescine synthesis.
Interferon-alpha inhibited increases in ornithine decarboxylase, intracellular putrescine, and DNA synthesis as human hepatoma cells were stimulated to grow. Interferon-alpha inhibited the increase in the c-myc protein level, but not its mRNA level. Added putrescine abrogated the effects on c-myc protein and DNA synthesis. Interferon-alpha seemed to inhibit the increase in the c-myc protein level post-transcriptionally by reducing the putrescine level, inhibiting DNA synthesis.
Blotting, Northern↗
Evidence for phosphoramidon-sensitive conversion of big endothelin-1 to endothelin-1 in isolated rat mesenteric artery.
The effect of phosphoramidon, a metalloproteinase inhibitor, on the pressor response to big endothelin-1 (big ET-1) in the isolated perfused rat mesenteric artery was examined. Big ET-1 (10(-9)-10(-7) M) caused a concentration-dependent increase in the perfusion pressure. The pressor response was markedly suppressed by phosphoramidon (10(-5) M). The inhibitor did not influence the ET-1 (5 X 10(-11)-10(-8) M)-induced pressor action. Big ET-1 (5 X 10(-8) M)-induced pressor action was accompanied by an increase in immunoreactive (IR)-ET in the perfusate, and this increase was suppressed by the addition of phosphoramidon. IR-ET in the perfusate was confirmed to be ET-1, as determined by reverse-phase HPLC. These findings strongly suggest that phosphoramidon-sensitive metalloproteinase contributes to the conversion of big ET-1 to ET-1, in vivo.
Animals↗
Therapeutic efficacy of interferon on HCV-RNA in chronic hepatitis C.
The efficacy of interferon therapy for chronic hepatitis C were evaluated by the changes of serum RNA of the hepatitis C virus (HCV) by the polymerase chain reaction. Before the treatment, HCV-RNA was detected in all of the 17 patients. 5 patients given IFN for 4 weeks, 12 cases given IFN by the 2 weeks/on 2 weeks off schedule (4 cases given 4 cycles and 8 given 6 cycles). Immediately after the treatment ended, the HCV-RNA was not detected in 12 (71%) cases. Five cases were persistently positive for HCV-RNA and showed continuously abnormal level of ALT. In 7 of 12 cases who became negative for HCV-RNA just after the treatment ended, HCV-RNA was detected again at first and 12th month after therapy. The ALT level were continuously abnormal in 4 of these 7 cases during and after the treatment, and became normal transiently in the other 3. In the 5 cases who became persistently negative (at least 1 year), ALT level decreased to normal or near-normal during follow up for more than one year. According to our results, we classified the therapeutic efficacy of IFN therapy for chronic hepatitis C. Type I response is complete response. In this type, HCV-RNA became negative persistently and ALT became normal or near-normal for at least 12 months after therapy. Type II is partial response. In this type, HCV-RNA became negative transiently and ALT level was transiently normal or poor. Type III is ineffective. In this type, HCV-RNA did not become negative and the effect for ALT was poor.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of single ethanol administration on hepatic ornithine decarboxylase induction and polyamine metabolism.
The effects of a single ethanol administration on ornithine decarboxylase induction, polyamine metabolism and DNA synthesis in rat liver after partial hepatectomy were studied. Ethanol given 1 hr before partial hepatectomy at the dose of 2, 3 or 5 gm/kg body wt inhibited the increase in ornithine decarboxylase activity and that in the putrescine level in the liver 4 hr after partial hepatectomy. The hepatectomy increased the amount of ornithine decarboxylase messenger RNA expressed, and this amount was unaffected by ethanol administration. Further, ethanol did not accelerate the degradation of ornithine decarboxylase 4 hr after partial hepatectomy, indicating that the inhibition of ornithine decarboxylase activity caused by ethanol was not caused by a decrease in the ornithine decarboxylase messenger RNA level or by the acceleration of ODC degradation. The single dose of ethanol inhibited [3H]thymidine incorporation into the hepatic DNA 24 hr after partial hepatectomy. The suppression of [3H]thymidine incorporation was partially reversed by the administration of putrescine. These results suggested that ethanol inhibits the increase in ornithine decarboxylase activity after transcription, suppressing the accumulation of putrescine, which prevents DNA synthesis in response to hepatectomy.
Animals↗
Mother-to-child transmission of hepatitis C virus.
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Female↗
Detection of hepatitis C virus antibodies and hepatitis C virus RNA in patients with alcoholic liver disease.
The relationship between alcoholic liver disease and hepatitis C virus was studied in 80 patients by searching for hepatitis C virus RNA with the polymerase chain reaction and by measuring hepatitis C virus antibodies. By C-100 enzyme-linked immunosorbent assay, hepatitis C virus antibodies were found in 2 of 10 patients with fibrosteatosis, 8 of 20 patients with alcoholic hepatitis, 14 of 19 patients with chronic hepatitis and 19 of 31 patients with cirrhosis. Percentages of patients with antibodies found by C-100 radioimmunoassay and by enzyme-linked immunosorbent assay based on sequence peptide 42 were lower; of the 16 patients with a low titer by C-100 enzyme-linked immunosorbent assay, 10 were negative by radioimmunoassay and 6 were negative by sequence peptide 42. By a second-generation recombinant immunoblot assay, hepatitis C virus antibodies were found in 1 of 10 patients with fibrosteatosis, 2 of 20 patients with alcoholic hepatitis, 15 of 19 patients with chronic hepatitis and 18 of 31 patients with cirrhosis. Hepatitis C virus RNA was found in 1 of 10 patients with fibrosteatosis, 3 of 20 patients with alcoholic hepatitis, 13 of 19 patients with chronic hepatitis and 20 of 31 patients with cirrhosis. Of the 37 patients with hepatitis C virus RNA, 31 had antibodies by C-100 enzyme-linked immunosorbent assay (25 patients at a high titer [cut-off index greater than 6]), and 31 had antibodies by second-generation recombinant immunoblot assay. Patients with cirrhosis and hepatitis C virus RNA had higher ALT activity than such patients without hepatitis C virus RNA (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Effects of single ethanol administration on liver regeneration in rats].
The effects of a single ethanol administration on liver weight gain, RNA synthesis, DNA synthesis, and polyamine metabolism as parameters of liver regeneration in rat liver after partial hepatectomy were studied. Ethanol, given 1 hr before partial hepatectomy at the dose of 3 g/kg, inhibited RNA synthesis 4 hr after partial hepatectomy and DNA synthesis 24 hr after partial hepatectomy in the liver, but did not affect liver weight gain. Further, we studied the effects of a single ethanol administration on polyamine metabolism in order to elucidate the mechanism of the inhibition of liver regeneration by ethanol. Ethanol inhibited the increase in the putrescine level in the liver 4 and 8 hr after surgery, which was a metabolic product of ornithine decarboxylase. But spermidine and spermidine levels in the liver were not affected by ethanol administration. Hepatic spermidine N1-acetyl transferase activity increased by ethanol administration 6 hr after partial hepatectomy in compensation for the suppression of putrescine. Judging from these results, a single dose of ethanol inhibited liver regeneration polyamine metabolism after partial hepatectomy in rats.
Acetyltransferases↗
Antithrombin III Kumamoto: identification of a point mutation and genotype analysis of the family.
We previously reported a variant antithrombin III (AT III Kumamoto) associated with a 31-year-old female who suffered from recurrent thrombotic episodes. To define the molecular basis for the variant AT III, we used a combination of genomic amplification followed by cloning, sequencing, and hybridization with allele-specific oligonucleotide probes. We obtained evidence for a cytosine to thymine transition in exon 2 (codon 47) of the AT III gene in the proband. This mutation converts arginine 47 to cysteine. Oligonucleotide hybridization procedures were used for confirmation of the mutation and for genotype analysis of the family members.
Adult↗
Effects of putrescine on D-galactosamine-induced acute liver failure in rats.
We studied the effect of putrescine on acute liver failure caused in rats by two injections of 1 gm/kg D-galactosamine. The hepatic polyamine level rose only slightly in the D-galactosamine-injected rats treated with glucagon and insulin, and [3H]thymidine incorporation into DNA increased little; these hormones did not improve the survival rate. When D-galactosamine-injected rats were given putrescine, the putrescine concentration in the liver increased and the survival rate of the rats was significantly higher than that of control rats given only D-galactosamine. Putrescine administration tended to lower the serum level of alanine aminotransferase in rats injected with D-galactosamine, so the polyamine might have a protective effect on hepatocytes. Putrescine significantly increased [3H]thymidine incorporation in the liver; thus it accelerated liver regeneration. Difluoromethylornithine decreased the level of putrescine in the liver, decreasing both [3H]thymidine uptake and the survival rate. In the rats treated with D-galactosamine, in which liver damage was so severe that treatment with glucagon and insulin was ineffective, the intraperitoneal administration of putrescine increased the survival rate in acute liver failure. This probably resulted mainly from activation of liver regeneration and possibly from a protective effect of putrescine on the liver.
Alanine Transaminase↗
Changes in interferon receptors on peripheral blood mononuclear cells from patients with chronic hepatitis B being treated with interferon.
We studied the binding of 125I-labeled human interferon-alpha to peripheral blood mononuclear cells and the activity of 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells obtained from 21 patients with chronic hepatitis B who were treated with human interferon-alpha or interferon-beta. Fourteen patients were given interferon daily for 4 wk. Interferon receptors per cell decreased to about 50% of baseline but increased to baseline by 2 wk after therapy ended. The activity of 2',5'-oligoadenylate synthetase rose about fivefold during therapy, decreasing to baseline by 1 wk after the end of therapy. The seven other patients were given interferon daily for 2 wk, no interferon for 2 wk and then interferon daily for 2 wk more. During both periods of therapy on this schedule, interferon receptors decreased to about 50% but returned to baseline 1 wk after the interferon was stopped. The activity of 2',5'-oligoadenylate synthetase increased about fivefold during both the first and second periods of therapy and decreased to baseline 1 wk after interferon was stopped. Close negative correlation existed between the number of interferon receptors and the 2',5'-oligoadenylate synthetase activity. The results of interferon therapy could not be predicted by either the numbers of interferon receptors before therapy or by the decrease in this number during therapy.
2',5'-Oligoadenylate Synthetase↗
[Clinical investigation of orthodontic treatment of palatally impacted canines, using ballista spring appliance].
Impacted maxillary caries are often treated in the orthodontic practice. However palatally impacted maxillary canines occur in a small. They require active orthodontic traction in those cases in which surgical exposure alone will not be enough to erupt. The purpose of this article is to describe useful orthodontic treatment for the palatally impacted caries by using the ballista spring appliance. Case 1: A girl 12 years 5 months of age had Angle Class 1 malocclusion with anterior cross bite and crowding teeth. Case 2: A woman 28 years 2 month of age had Angle Class 1 malocclusion with crowding teeth. The results were as follows: 1. After the impacted canines retracted and guided into the dental arch in correct position, the condition of the canines and tissues around have been stabilized. 2. The ballista spring appliance was effective in pulling the palatally impacted maxillary canines forward vertical direction.
Adult↗
[Interferon-alpha/beta receptors in patients with chronic HBV infection].
We analyzed the binding of 125I-labelled IFN-alpha to peripheral blood mononuclear cells in 19 healthy controls, 25 asymptomatic HBV carriers (AsC), and 69 patients with HBs antigen positive chronic liver disease (CLD). Histological examination showed that of the 69 patients with CLD, 14 had chronic persistent hepatitis (CPH), 46 had chronic active hepatitis (CAH), 9 had liver cirrhosis (LC). The mean number of IFN-alpha/beta receptor sites per cell totaled 1270 +/- 340 in the healthy controls, 1440 +/- 290 in AsC, and 1600 +/- 480 in CLD (with 1770 +/- 480 in CPH, 1580 +/- 490 in CAH, and 1420 +/- 410 in LC). HBV carriers had more IFN-alpha/beta receptor sites than the healthy controls (AsC: P less than 0.1, CLD: P less than 0.01). In CLD, patients with LC tended to have fewer IFN-alpha/beta receptor sites than those with CPH or CAH. The number of IFN-alpha/beta receptor sites in CLD was correlated with the HBe antigen titer (P less than 0.01), and activity of HBV-DNA polymerase (P less than 0.05). These results were suggested that IFN-alpha/beta receptor sites was higher at the HBV carrier state, and correlated with viral replication.
Carrier State↗
[Rapid prenatal diagnosis of familial amyloidotic polyneuropathy using DNA amplification].
We have used in vitro DNA amplification by the polymerase chain reaction for prenatal diagnosis of familial amyloidotic polyneuropathy (FAP) in a German family. Fetus DNA was prepared from chorionic villus sampling and specific prealbumin DNA sequence that may carry FAP type I mutation was enzymatically amplified. The mutant prealbumin gene could be distinguished by direct DNA analysis with Nsi I using amplified DNA. This method is sufficiently sensitive and rapid that prenatal diagnosis of FAP can be done on the same day when fetal DNA is available.
Amyloidosis↗
[DNA diagnosis of amyloidoses].
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Adolescent↗
Prediction of esophageal varices in cirrhosis by per-rectal portal scintigraphy.
Portal circulation in patients with chronic liver disease was evaluated by per-rectal portal scintigraphy, and per-rectal portal shunt indices were calculated to estimate the extent of the portosystemic shunt. The purpose was to identify patients with cirrhosis at special risk of developing esophageal varices. The cumulative incidence of varices in 3 years of the study in patients whose shunt index was originally 20% or over, was significantly higher than that in patients whose shunt index was originally under 20%. The cumulative survival rate in 7 years of the study in patients whose shunt index was originally under 70% was significantly higher than that in patients whose shunt index was originally 70% or over. The information obtained by calculating the shunt index could be used by physicians in out-patient clinics when deciding the schedule with which to monitor patients using barium esophagogram or endoscopy, and choosing the examination method.
Esophageal and Gastric Varices↗