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S Nishiguchi

Publications and source records attributed to S Nishiguchi.

At least 109 records · Page 6Linked to original sources
PubMed1997

A survey of genes expressed in mouse embryonal carcinoma F9 cells: characterization of expressed sequence tags matching no known genes.

We prepared 2,132 expressed sequence tags (ESTs) from undifferentiated mouse embryonal carcinoma F9 cells and found that 1,416 match known gene and/or protein sequences [Nishiguchi et al. (1996) J. Biochem. 119, 749-767]. To obtain information on the functions of the remaining 716 unidentified ESTs and to develop a system for characterizing ESTs matching no known genes, we analyzed their sequences by (i) repeated database searches, using the BLASTN, BLASTX, TBLASTX, and FASTA programs, (ii) using computer programs developed or modified for this work, such as the WFASTA, ORFTRNS, and MFASTA programs, together with the DBPROSITE and GRAIL programs, and (iii) examining the expression patterns of the corresponding mRNAs in F9 cells and several organs of adult mice, using the digoxigenin-labeled dot-blot method. We found that 216 of the 716 ESTs match known gene and/or protein sequences, and 307 show significant similarities to these sequences, with a Poisson p-value < 0.01. The strategy and usefulness of such analysis for characterizing unidentified ESTs are discussed.

Animals↗
PubMed1997

Evaluation of fulminant hepatic failure by scintigraphy with technetium-99m-GSA.

UNLABELLED: We evaluated the usefulness of hepatic receptor imaging with 99mTc-diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) to establish the diagnosis and prognosis of fulminant hepatic failure (FHF). METHODS: Of the 20 patients, 8 had acute hepatitis and 12 had FHF. Computer acquisition of gamma-camera data started just before the injection of 185 MBq 99mTc-GSA and stopped 20 min later. Time-activity curves for the heart and liver were generated from regions of interest (ROIs) for the whole liver and precordium. A receptor index was calculated by division of the radioactivity of the liver ROI by that of the liver plus heart ROIs 15 min after the injection. An index of blood clearance was calculated by division of the radioactivity of the heart ROI at 15 min by that of the heart ROI 5 min after the injection. RESULTS: The receptor index was less than 0.83 in all patients with FHF, but it was more than 0.83 in all patients with acute hepatitis. The index of blood clearance was more than 0.72 in all patients with FHF but less than 0.72 in all patients with acute hepatitis. All six survivors of FHF had receptor indices of 0.58 or more, but in five of the six patients who later died, the receptor index was 0.58 or less. The index of blood clearance was 0.85 or less in all survivors but 0.85 or more in the same five patients who later died. CONCLUSION: Hepatic receptor imaging with 99mTc-GSA facilitated the evaluation of hepatic function reserve and was useful in establishing the diagnosis and prognosis of FHF.

Acute Disease↗
PubMed1997

Changes in results of Gallium-67-citrate scanning after interferon therapy for chronic hepatitis C.

UNLABELLED: Gallium-67 scanning is useful for early diagnosis and grading of interstitial lung disease. In a study of the side effects of interferon (IFN) on the lungs of patients with chronic hepatitis C, we performed 67Ga scanning before and after IFN therapy. METHODS: The 66 subjects who underwent at least one scanning, before IFN therapy, were 8 patients with chronic persistent hepatitis (CPH), 21 with chronic aggressive hepatitis 2A (CAH-2A), 25 with chronic aggressive hepatitis 2B (CAH-2B) and 12 with cirrhosis. All had underlying hepatitis C viral infection. Of those patients, 20 were examined again within 1 mo after IFN therapy. Patients received an intravenous injection of 340 MBq 67Ga-citrate and were imaged 72 hr later. ROIs were established for anterior views of the lungs (Lu), liver (Li) and soft tissue of the upper arm as background (B). The counts per unit size of each region of interest were used in calculation of the ratios Lu/B and Li/B. RESULTS: The medians of Lu/B were 2.46 in CPH, 2.56 in CAH-2A, 2.50 in CAH-2B and 2.47 in cirrhosis. These differences were not statistically significant. The medians of Li/B were 6.42 in CPH, 6.14 in CAH-2A, 5.11 in CAH-2B and 4.03 in cirrhosis. The differences between the median Li/B of cirrhotic patients and the medians for patients with CPH, CAH-2A and CAH-2B were significant. After therapy, Lu/B was higher than before in 16 of the 20 patients and lower in the four other patients; the overall rise was significant (Wilcoxon rank-sum test). Li/B was higher than before in 11 of the 20 patients and lower in the nine other patients. CONCLUSION: IFN caused uptake of the radionuclide to increase in most patients. This method showed changes in the accumulation of 67Ga-citrate that could have been missed if the results had been inspected by eye. IFN can cause interstitial lung disease, but unlike other drugs with this side effect, the onset seems to be gradual enough to be detected quantitatively by 67Ga scanning.

Adult↗
PubMed1996

A catalogue of genes in mouse embryonal carcinoma F9 cells identified with expressed sequence tags.

We used expressed sequence tags (ESTs) to identify genes expressed in mouse embryonal carcinoma F9 cells and prepared 2132 ESTs from undifferentiated F9 cDNA libraries: 1026 were prepared after randomly selecting clones from one of the libraries and the remaining 1106 ESTs were prepared after classifying 2896 clones of the libraries into four classes, according to the levels and patterns of expression. Among the former 1026 ESTs, 797 (78%) matched known genes, 61 (6%) matched database sequences of uncharacterized cDNAs, and 168 (16%) represented novel genes. The ESTs matching known genes were catalogued according to putative structural and cellular functions. As many as 53% were related to transcription and translation, and 19% were related to energy metabolism, including transcripts of mitochondrial DNA. These percentages were significantly higher in F9 cells than in the human heart and brain, and a human liver cell line, HepG2. We found that approximately 7% of the ESTs corresponding to low-abundance mRNAs are either related to retinoic acid-regulated genes or mammalian development- and/or differentiation-related genes. Cataloguing of the genes expressed in the F9 cells paves the way for isolating genes involved in early mammalian development.

Adult↗
PubMed1996

Effect of vitamin E deficiency on inhibition of liver regeneration by long-term administration of alcohol.

The effects of vitamin E (VE) deficiency on liver regeneration suppressed by long-term administration of alcohol were studied. Male rats were divided into two groups: the alcohol group and the control group. In addition, each group was subdivided into two groups according to the presence or not of VE. Altogether, four groups were provided: a group maintained on the VE-deficient alcohol diet (group EA), a group maintained on the VE-deficient control diet (group EC), a group maintained on the ordinary alcohol diet (group A), and a group maintained on the ordinary control diet (group C). After pair-feeding for 6 weeks, partial hepatectomy was performed to determine the omithine decarboxylase (ODC) activity, polyamine levels, lipid peroxide levels, and DNA synthesis, DNA synthesis at 24 hr after partial hepatectomy was suppressed significantly in the alcohol administration group, regardless of the presence or not of VE DNA synthesis at 48 hr after partial hepatectomy tended to show low values in group EA, compared with group A. As for the hepatic ODC activity, group EA showed the lowest value at 4 hr after partial hepatectomy. Of polyamines, the putrescine level in group EA at 4 hr after partial hepatectomy was significantly low, compared with the other three groups. The levels of spermidine and spermine decreased by long-term administration of alcohol, but the effect of VE deficiency was not found. The lipid peroxide level increased significantly in the VE-deficient diet administration group, but the effect of alcohol administration was not found. These results suggested that the decrease in putrescine after ODC suppression by VE deficiency in addition to the decrease in spermidine and spermine caused by long-term alcohol administration were concerned with suppression of DNA synthesis later.

Animals↗
PubMed1996

Hepatic distribution of blood flow from the superior or inferior mesenteric vein mapped by portal scintigraphy with iodine-123-iodoamphetamine.

UNLABELLED: We previously reported the clinical meaning of measurements of the relative contributions of the superior and inferior mesenteric veins with [123I]iodoamphetamine after oral (in an enteric capsule) and rectal administration. The same method was used to map blood flow in the liver from both of these veins in 82 subjects, 31 with chronic hepatitis and 51 with cirrhosis. METHODS: Three hours after administration of a capsule containing 22.8 MBq of [123I]iodoamphetamine, data showing hepatic blood flow from the superior mesenteric vein were collected for 10 min. Next, 111 MBq of [123I]iodoamphetamine was administered rectally and data showing hepatic blood flow from the inferior mesenteric vein were collected for 30 min. Shunt indices from the superior and inferior mesenteric veins were calculated from these data. RESULTS: In patients with chronic hepatitis, blood from the superior mesenteric vein flowed into the right lobe or both lobes, but, in some patients with cirrhosis, blood from this vein flowed into the left lobe. In some patients with chronic hepatitis, blood from the inferior mesenteric vein flowed into the left lobe, but, in most patients with cirrhosis, the liver was not visualized during this examination and evaluation was not possible. Of the 53 patients in whom blood flow from both veins could be evaluated, 47 had blood from the two veins mixed to some extent in the liver and 6 had portal streamlining, with blood from the superior mesenteric vein going to the right lobe and blood from the inferior mesenteric vein going to the left lobe. CONCLUSION: These results suggest that blood flow in the superior and inferior mesenteric veins can be found mixed in the liver in most subjects with liver disease.

Amphetamines↗
PubMed1996

Diagnosis by routine scintigraphy of hepatic reticuloendothelial failure before severe liver dysfunction.

OBJECTIVES: The prognosis of hepatic reticuloendothelial failure is said to be poor. Scanning with the radiocolloid 99mTc phytate is needed for diagnosis; as a rule; only seriously ill patients are so investigated. We use 99mTc phytate for liver scans of almost all inpatients with liver disease. This routine made diagnosis of a mild form or early stage of the disease possible. We evaluated the clinical findings of the five patients we have diagnosed, in an attempt to find why four survived. METHODS: Radiocolloid scans were taken starting 20-30 min after the intravenous injection of 111 MBq of 99mTc phytate. Hepatobiliary images were taken by use of 99mTc pyridoxylidine-5-methyl trytophan, and hepatic receptor images were taken by use of 99mTc-labeled diethylenetriaminepentaacetic acid coupled with galactosyl human serum albumin. RESULTS: The livers were not visible in the radiocolloid scans, so the diagnosis of hepatic reticuloendothelial failure was considered. In the two other imaging examinations, the livers were visible. The cause was identified as heavy alcohol intake in four cases and toluene hepatotoxicity in one case. Histological examinations showed cirrhosis in two patients; the three other patients did not have cirrhosis. All five patients had anemia, and three had infections. One patient died of multiple organ failure, and the four other patients survived. Long-term observation by radiocolloid scanning was possible in one patient in whom radionuclide uptake into the liver rose as hepatic function improved. CONCLUSIONS: This disorder is associated with a temporary decrease in Kupffer cell function and hence is liable to be complicated by infection, which can result in death. If the cause is removed promptly, recovery is likely. There being a mild form of this disease, previously not generally diagnosed, probably accounts for the outcomes being good in all of our patients except the one patient with severe liver dysfunction at the time of diagnosis.

Adult↗
PubMed1995

A replacement vector used to introduce subtle mutations into mouse genes.

A replacement vector convenient for introducing subtle mutations into various mouse genes has been developed using, a model system, the mouse transthyretin-encoding gene (ttr) and mouse embryonal carcinoma F9 cells. The vector consists of part of ttr carrying a subtle mutation in its second exon, and a cassette of the neomycin-resistance (neo)- and herpes simplex virus thymidine kinase (HSV-tk)-encoding genes flanked with a 3-kb duplication of mostly the second intron of ttr. In the first step ('replacement'), part of the endogenous ttr was replaced by vector DNA via homologous recombination, and two such clones, #33 and #77, were isolated from 185 G418-resistant clones by allele-specific PCR. In the second step ('excision'), gancyclovir-resistant colonies were screened, and 7 and 84% of those isolated from clones #33 and #77, respectively, were demonstrated to carry the subtle mutation in ttr, without the cassette of selection markers. In five independently isolated random integrants of the same vector DNA, the cassette of selection markers was excised efficiently by recombination within the duplication.

Animals↗
PubMed1995

Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.

Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients but whether it prevents carcinogenesis is unknown. In a prospective randomised controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma. 90 patients with compensated chronic active hepatitis C with cirrhosis were randomly allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45 patients) or symptomatic treatment (45 controls), and were followed up for 2-7 years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80 IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not significantly different between the two groups. The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls (p = 0.021). The mean change in the serum albumin level was higher in the IFN-alpha group (p < 0.001). The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%) and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p = 0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional hazards). IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis, and its use was associated with a decreased incidence of hepatocellular carcinoma.

Antineoplastic Agents↗
PubMed1995

Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma.

Ornithine decarboxylase (ODC) plays an important role in cell growth, and its activity is regulated by many mechanisms. The biochemical characteristics of ODC in malignant cells differ from those of ODC in normal cells. To determine whether novel changes occur in ODC in neoplastic tissue, we compared the nucleotide sequence of ODC cDNA obtained from human hepatoma tissue as determined by reverse transcriptase-PCR with that of ODC cDNA obtained from nontumorous tissue in the same patients. There were three point mutations accompanied by replacements of amino acids in hepatoma tissue with other amino acids or a stop codon. In one poorly differentiated hepatoma, codon 415, CAA was converted to TAA, resulting in replacement of Gln-415 by a stop codon. The mutated ODC protein produced by translation in a reticulocyte-lysate protein synthesizing system was truncated and stabilized in an ATP antizyme-dependent degradation system. These findings suggest that formation of a truncated and stabilized ODC protein due to point mutation is one reason why ODC activity is high in human hepatoma tissue.

Base Sequence↗
PubMed1995

Evaluation of portal circulation through the superior mesenteric vein with an enteric capsule of [123I]iodoamphetamine.

We report a method by which the contribution of the superior mesenteric vein to the portal blood flow can be evaluated noninvasively. An enteric-coated capsule containing [123I]iodoamphetamine is given by mouth 3h before the examination. The data obtained are treated by computer to calculate the portal shunt index (SI) through the superior mesenteric vein. The SI was higher for more severe liver disorders, Increasing in the order of chronic persistent hepatitis, chronic aggressive hepatitis, and cirrhosis. The SI was higher in cirrhotic patients than in chronic hepatitis patients or healthy volunteers (both, P < 0.0001). The SI was higher in cirrhotic patients with esophageal varices than in such patients without varices (P < 0.05). The SI was higher in cirrhotic patients with ascites than in such patients without ascites (P < 0.001). The SI was higher in cirrhotic patients with encephalopathy than in those without encephalopathy (P < 0.01). Correlation was significant between the SI and classical indicators of functional reserve. This method is clinically useful.

Administration, Oral↗
PubMed1995

Primary biliary cirrhosis complicated by severe hypoxemia.

The case reported here is of a 61-year-old woman diagnosed with hepatopulmonary syndrome. She had had severe hypoxemia for 5 years. In room air, her arterial oxygen tension was low, and although we anticipated that treatment with oxygen would increase it, the treatment failed to do so. Pulmonary perfusion imaging with Tc-99m-labelled macroaggregated albumin showed an arterio-venous shunt in the lungs. Blood tests and liver scanning with Tc-99m-labelled galactosyl human serum albumin showed abnormalities of liver function, and per-rectal portal scintigraphy with Tc-99m pertechnetate showed severe portal hypertension. Inspection of a biopsy specimen taken under ultrasonographic guidance showed primary biliary cirrhosis of Scheuer stage I. The causes of hepatopulmonary syndrome are unknown, but seem to include a decrease in hepatic functional reserve, portal hypertension, or other factors. The development of hepatopulmonary syndrome due to portal hypertension in this patient is of interest.

Biopsy↗