[Natural course of infants with hepatitis C virus].
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Female↗
Biomedical subjects
S Nishiguchi
Publications and source records attributed to S Nishiguchi.
[Clinical characteristics of HBV and HCV coinfection in patients with chronic hepatitis].
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Chronic Disease↗
Clinical usefulness of evaluation of portal circulation by per rectal portal scintigraphy with technetium-99m pertechnetate.
OBJECTIVE: Portal circulation, in particular the contribution of the inferior mesenteric vein, can be evaluated in a relatively noninvasive way by per rectal portal scintigraphy (J Nucl Med 1988; 29:460-5). The clinical usefulness of the method was evaluated. METHODS: A solution containing technitium-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. By analyses of the curves, the per rectal portal shunt index (SI) was calculated. RESULTS: The SI was higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis, and the SI was higher in cirrhotic patients than in patients with chronic hepatitis or in healthy subjects. The SI was significantly higher when a complication (varices, ascites, or encephalopathy) was present. Correlation between the SI and classic indicators for functional reserve was significant. The SI was significantly related to survival according to results of regression analysis by Cox's proportional hazards model. On the basis of the SI when patients were first examined, the patients with cirrhosis were divided into three groups of roughly equal size: group A, SI under 30%; group B, SI between 30 and 70%; and group C, SI over 70%. The survival rate was lower in group B than in A, lower in group C than in A, and lower in group C than in B. CONCLUSIONS: This method is clinically useful, especially in establishing the prognosis.
Humans↗
Use of immobilized histidine in assay for endotoxin in patients with liver disease.
The Limulus amebocyte lysate (LAL) test has the disadvantage of being influenced by various inhibitors and activators. We have developed a method for the LAL reaction that involves the specific adsorption and isolation of endotoxin using a membrane filter unit and immobilized histidine; in this present study we used the method to measure endotoxin in the plasma of patients with acute or chronic liver disease. The adsorbed endotoxins are separated from LAL-inhibitors or -activators by the membrane filter unit, and their activity is directly assayed with the LAL reagent in a filter cup without any inhibition or activation. The study population consisted of 23 subjects, 3 with fulminant hepatitis and 20 with cirrhosis (9 with esophageal varices and 11 without). All 3 (100%) of the samples of plasma from patients with fulminant hepatitis were positive for endotoxin, as were the samples of 7 (78%) of the 9 patients with cirrhosis and esophageal varices, and 2 (18%) of the 11 patients with cirrhosis but without such varices. The results suggested that this method appears to be useful for assaying the concentration of endotoxin in patients with fulminant hepatitis or cirrhosis of the liver.
Acute Disease↗
Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women, evaluated by dual-energy X-ray absorptiometry.
To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirrhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P < 0.001) and in those with cirrhosis of the liver (P < 0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone.
Absorptiometry, Photon↗
Structures of replacement vectors for efficient gene targeting.
The relationship between DNA structure of replacement vectors and gene targeting efficiency was studied using positive-negative selection. The vectors contained pBR322 DNA, a bacterial neomycin-resistance gene (neo) for positive selection, a herpes simplex virus (HSV) thymidine kinase gene (tk) for negative selection, and a mouse genomic fragment, including exons 1 to 3 of the transthyretin (ttr) gene. The neo gene that confers G418 resistance was inserted into the second ttr exon, and the HSV-tk gene that confers gancyclovir (GANC) sensitivity was added to the 3' end of the ttr fragment. The vectors were linearized by digesting with restriction enzyme(s) and transfected into mouse embryonal carcinoma F9 cells. In this system, the enrichment by GANC selection as well as the frequency of gene targeting was increased by placing the pBR322 DNA at the 3' end of the HSV-tk gene. Adding one more HSV-tk gene at the 5' end of the ttr fragment did not increase the enrichment by GANC selection. This enrichment factor was also increased by reducing the size of the ttr fragment present between the two selection markers. However, it decreased the frequency of gene targeting and, overall, it did not increase the efficiency of isolating targeted clones. When structures of the vector DNA fragments present in 20 G418-resistant and GANC-resistant non-targeted clones were examined by Southern blot analysis, the inefficiency of GANC selection proved to be mostly caused by exonucleolytic degradation of HSV-tk genes progressing from ends of the vectors.
Animals↗
A survey of genes expressed in undifferentiated mouse embryonal carcinoma F9 cells: characterization of low-abundance mRNAs.
As a first step to catalogue mRNAs present in mouse embryonal carcinoma F9 cells, 879 clones corresponding to low-abundance mRNAs were selected from among 2,896 randomly picked up clones of undifferentiated F9 cDNA libraries, using DNA probes complementary to poly(A)+RNAs prepared from undifferentiated F9 cells and to ones prepared from mouse fibroblast L cells. Five-hundred and eighty-two of the 879 clones were partially sequenced, and the subsequent homology search revealed that 201 corresponded to 180 known genes or known DNA sequences, which include not only housekeeping genes but also various tissue-specific genes. Interestingly, at least 24 of the 180 genes are development-related genes in mammals. Among these 24, those for midkine (growth and/or differentiation factor) and interferon-beta are reportedly up-regulated, and those for ECA39 (target for c-Myc regulation), REX-1 (zinc finger protein), and OCT-3 (POU-domain transcription factor) are down-regulated during the development of mouse embryonal carcinoma cells. Thirty-seven of the 582 clones matched the 36 previously reported unidentified ESTs (expressed sequence tags) and the remaining 344 corresponded to 329 novel ESTs. Therefore, partial sequencing of F9 cDNA clones corresponding to low-abundance mRNAs in F9 cells not only provides valuable information concerning development-related genes in mammals, but also many novel ESTs useful for studying mammalian genomes.
Animals↗
Relationship of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma.
To evaluate the correlation between the polyamine metabolism and the degree of malignancy in hepatocellular carcinoma, we measured ornithine decarboxylase activity and polyamine concentrations in neoplastic tissue and adjacent noncancerous tissue from resected specimens of liver from 30 patients. Ornithine decarboxylase activity, polyamines (putrescine, spermidine and spermine) and ornithine decarboxylase mRNA levels were significantly higher in hepatoma tissue than in noncancerous tissue. The activity of this enzyme in the tumor tissue had a negative correlation with the histological degree of differentiation judged according to a modification of the Edmondson and Steiner classification. Resected hepatoma tissue was stained immunohistochemically with antibodies for proliferating cell nuclear antigen (also called cyclin), a marker of cell proliferation. We noted correlation between ornithine decarboxylase activity and the number of cells stained for this antigen (r = 0.882, p < 0.001). These results indicate that ornithine decarboxylase activity is high in human hepatocellular carcinoma, leading to increased intracellular concentrations of polyamines. Ornithine decarboxylase activity also reflected the rate of tumor proliferation and was correlated with the histological findings.
Adult↗
[The managements of nutrition for hepatic cirrhosis].
Hepatic cirrhosis is the end stage in chronic liver diseases and this condition cause the patient's death because of hepatic failure. A prognosis of patients with hepatic cirrhosis depend on the liver function, especially the function of mass of residual hepatocytes and this function expressed by level of serum albumin, cholinesterase (Ch E) or ICGR-15. This function is improved a management of nutrition because hepatocytes are regenerate by intake of protein. In compensated hepatic cirrhosis, hepatocytes are regenerate by dietary intake of 100-120 g/day of protein and the function of mass of residual hepatocytes is increased. The prognosis of these patients with compensated hepatic cirrhosis are improved by this management of nutrition.
Dietary Proteins↗
Measurement of portal systemic shunting by oral and per-rectal administration of [123I]iodoamphetamine, and clinical use of the results.
UNLABELLED: OBJECTIVE. We used a method by which the portal shunt index via the superior mesenteric vein (SI-S) and that via the inferior mesenteric vein (SI-I) could be evaluated simultaneously. The clinical usefulness of the method was studied. METHODS: Scintigraphy was done 3 h after subjects took an enteric-coated capsule containing [123I]iodoamphetamine. At that time, the radionuclide was injected into the rectum. Counts for the lungs and the liver were used to calculate the two shunt indices. RESULTS: The mean SI-S and SI-I tended to be higher for disorders that were more severe, increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis. In cirrhotic patients, the SI-I was higher than the SI-S (p < 0.001). The SI-S and SI-I were both higher in cirrhotic patients with esophageal varices than in such patients without varices (p < 0.05 and < 0.001). The SI-S and SI-I were higher in cirrhotic patients with ascites than in such patients without ascites (p < 0.001 and < 0.01). Correlation between either of these indices and classical indicators of functional reserve was high. The correlation of SI-S with the Child-Turcotte classification and total bilirubin level was higher than the correlation of the SI-I and these indicators of functional reserve. CONCLUSIONS: This method permits assessment of the portal hemodynamics in a relatively noninvasive way, and is clinically meaningful.
Administration, Oral↗
Effect of combined alanine and glutamine administration on the inhibition of liver regeneration caused by long-term administration of alcohol.
We studied the effect of administration of a mixture of alanine and glutamine on the inhibition of liver regeneration caused by alcohol in rats undergoing partial hepatectomy 6 weeks after the start of alcohol administration. DNA synthesis was inhibited 24 hr after partial hepatectomy in rats given alcohol, but treatment with alanine and glutamine partially prevented this inhibition. To identify the mechanism of this effect, polyamine metabolism was studied. Administration of alcohol or alanine plus glutamine had no effect on the activity of ornithine decarboxylase, a rate-limiting enzyme of polyamine metabolism. In the liver, of the three polyamines, only the spermine concentration changed significantly. It decreased during long-term administration of alcohol, and this decrease was prevented by treatment with alanine and glutamine. The level of N(1)-acetylspermidine, the acetylated product of spermidine, was increased by alcohol, and its elevation was significantly less when alanine and glutamine were given. Hepatic spermidine/spermine N(1)-acetyltransferase, the key enzyme of polyamine acetylation, was induced by long-term administration of alcohol, and this induction was suppressed by alanine plus glutamine. The results suggest that treatment with alanine and glutamine can help to prevent the inhibition of liver regeneration caused by alcohol by maintaining the spermine level and suppressing the acetylation of spermidine.
Alanine↗
Endothelium-independent pressor effect of big endothelin-1 and its inhibition by phosphoramidon in rat mesenteric artery.
We asked whether or not the endothelium plays a functional role in the conversion of big endothelin-1 to endothelin-1 in the perfused rat mesenteric artery. In endothelium-denuded preparations, big endothelin-1 produced a much more potent pressor effect than in intact preparations. Phosphoramidon suppressed the big endothelin-1-induced pressor action without affecting the action of endothelin-1, irrespective of the presence or absence of the endothelium. The amounts of immunoreactive-endothelin in the perfusate during perfusion of endothelium-denuded preparations with big endothelin-1 were extremely low compared with those observed in intact preparations and were not significantly suppressed by the metalloproteinase inhibitor, phosphoramidon, in contrast to the case with intact preparations. When synthetic endothelin-1 was perfused in the endothelium-denuded mesentery, the peptide disappeared from the perfusate more rapidly than with intact preparations, suggesting that endothelin-1 generated from big endothelin-1 is effectively trapped by vascular smooth muscle cells in the endothelium-denuded preparation. Our results suggest that the endothelium is not essential for the conversion of big endothelin-1 to endothelin-1, in rat mesenteric artery.
Animals↗
Disruption of the transthyretin gene results in mice with depressed levels of plasma retinol and thyroid hormone.
Transthyretin (TTR) is thought to play a major role in vitamin A metabolism and thyroid hormone transport in mammals. To investigate the physiological role of the TTR protein in development of the embryo and in the adult, we used gene targeting techniques to generate a null mutation at the mouse ttr locus. The resultant mutant animals are phenotypically normal, viable, and fertile. However, levels of serum retinol, retinol-binding protein, and thyroid hormone are significantly depressed in the mutant animals. These observations demonstrate that the TTR protein maintains normal levels of these metabolites in the circulating plasma.
Animals↗
Long-term therapeutic efficacy of interferon for patients with chronic hepatitis C.
Interferon is being used for therapy of chronic hepatitis C, but its long-term results have not been reported. We studied 65 patients with this disease who were monitored for at least 2 years after completion of the therapy. Almost all patients who had responded to therapy at 6 months after the end of therapy had normal levels of alanine aminotransferase (ALT) when evaluated later. The level of ALT became normal for the first time in some patients more than 6 months after therapy ended. The level of ALT in many of the patients without HCV RNA had become normal 6 months after the end of the therapy. One of three schedules was employed: three times weekly long-term; daily for two weeks and none for two weeks in a cycle; and daily for several weeks; 57%, 29%, and 17% of the patients on these schedules came to have normal ALT levels. Patients without HCV RNA at six months after completion of therapy tended to have higher responses in terms an increased level of 2',5'-oligoadenylate synthetase of mononuclear cells in vitro before therapy began. However, therapy three times per week was effective even for some patients judged not responsive to IFN by this test. The results showed that IFN therapy was effective for chronic hepatitis C when judged by long-term results.
Adult↗
Effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment.
We studied the effects of alanine and glutamine administration on the inhibition of liver regeneration by acute ethanol treatment after partial hepatectomy (PH) in rats. When rats were dosed i.p. with ethanol at 2 g/kg at the time of PH, DNA synthesis 48 hr after PH was significantly inhibited, but it was completely reversed by the combined use of alanine and glutamine. Although hepatic ornithine decarboxylase (ODC) activity in the alcohol-treated group 4 hr after PH was significantly inhibited, there was a tendency towards recovery of the ODC inhibition in the alanine and glutamine-treated group. The putrescine (PUT) level in liver which was decreased by ethanol was also increased by the administration of alanine and glutamine. However, the levels of spermidine (SPD) and spermine (SPM) in liver were unaffected either by ethanol or by alanine and glutamine. These results suggest that alanine and glutamine show a protective effect on the inhibition of liver regeneration caused by acute ethanol treatment by improving polyamine metabolism, particularly by increasing hepatic PUT levels.
Alanine↗
Absence of hepatic uptake of Tc-99m phytate in a man with chronic toluene hepatotoxicity.
The case reported here is of a 28-year-old man diagnosed as having toluene hepatotoxicity. He had a 5-year history of exposure to toluene and was admitted to hospital complaining of two episodes of loss of consciousness. The high total bilirubin and the low prothrombin time suggested serious liver dysfunction. Based on histologic examination of a liver biopsy specimen, the diagnosis of toxic liver dysfunction caused by toluene poisoning was made. Hepatic images were not present in Tc-99m phytate scintigrams, but they were present in hepatobiliary scintigrams done with the Tc-99m N-pyridoxyl-5-methyltryptophan. The diagnosis of hepatic reticuloendothelial failure was made.
Adult↗
Vertical transmission of hepatitis C virus (HCV) detected by HCV-RNA analysis.
The rate of transmission of hepatitis C virus (HCV) from patients with chronic hepatitis C to their children was studied. Of the 64 children with a parent with chronic hepatitis C, two (3%) had abnormal alanine aminotransferase (ALT) activities, six (9%) had anti-HCV detected by c100 ELISA, seven (11%) had anti-HCV detected by ELISA-II, and 21 (33%) had HCV-RNA by polymerase chain reaction (PCR). Anti-HCV detected by ELISA-II disappeared within six months in all six infants. Of the five children whose mothers were given a blood transfusion after the child's first birthday, none had anti-HCV or HCV-RNA. In the five families whose elder or eldest offspring had HCV-RNA, all of the younger offspring had HCV-RNA. The vertical transmission rate of HCV was low if judged by the presence of anti-HCV or abnormal ALT values, but the rate was high (33%) if judged by the presence of HCV-RNA.
Adolescent↗
Results of surgery for portacaval shunt in a patient with situs inversus diagnosed and evaluated by per rectal portal scintigraphy.
A 70-yr-old man diagnosed with situs inversus was hospitalized because of hepatic encephalopathy. Per rectal portal scintigraphy showed portal hypertension and a region with high radionuclide activity in the right lateral region of the abdomen. In percutaneous transhepatic portograms, a giant portacaval shunt was seen in the region with high radionuclide activity. After the portacaval shunt was obstructed surgically, the hepatic encephalopathy disappeared. In per rectal portal scintigraphy done 2 wk after surgery, the pattern was normal and the region with high radionuclide activity had disappeared.
Aged↗