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Biomedical subjects

S Nishiguchi

Publications and source records attributed to S Nishiguchi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Use of scintigraphy with 99mtechnetium galactosyl human serum albumin for staging of primary biliary cirrhosis and assessment of prognosis.

BACKGROUND: Conventional models for prediction of survival in patients with primary biliary cirrhosis (PBC) are based on the results of blood tests and on the clinical condition, which may be affected by treatment. We evaluated the usefulness of hepatic receptor imaging with [99mtechnetium]-diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) for the staging and prognosis of PBC without the need for reference to laboratory test results. METHODS: The subjects were 45 patients with PBC, 10 healthy subjects, 62 patients with chronic hepatitis and 144 patients with cirrhosis. Computer acquisition of gamma-camera data was started just before the injection of 185 MBq [99mTc]-GSA and was stopped 20 min later. Time-activity curves were generated from regions of interest (ROI) for the heart and liver. A receptor index was calculated by dividing the radioactivity of the liver ROI by that of the liver-plus-heart ROI 15 min after the injection. An index of blood clearance was calculated by dividing the radioactivity of the heart ROI 15 min after the injection by that of the heart ROI 3 min after the injection. RESULTS: The median receptor index was higher in patients with PBC than in those with cirrhosis. Among patients with PBC, the receptor index was lower in those with stage IV disease than in those in stages I, II or III. The index of blood clearance was lower in patients with PBC than in those with cirrhosis. Among patients with PBC, the index of blood clearance was higher in those with stage IV disease than in those in stages I, II or III. The receptor index was correlated significantly both to the risk score of the Mayo model and to the prognostic index of the Japanese model. The index of blood clearance was also correlated significantly to this score and prognostic index. CONCLUSIONS: Hepatic receptor imaging with [99mTc]-GSA is useful for the evaluation of hepatic functional reserve, staging of PBC and assessment of prognosis.

Asialoglycoprotein Receptor↗
PubMed1999

Correlation of clinicopathologic features of resected hepatocellular carcinoma with hepatitis C virus genotype.

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.

Aged↗
PubMed1999

Effects of continuous hepatitis with persistent hepatitis C viremia on outcome after resection of hepatocellular carcinoma.

The effect of persistent hepatitis C viremia on the outcome after resection of hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C virus (HCV) RNA was evaluated using a reverse transcription polymerase chain reaction method as well as a branched DNA probe method. Clinicopathologic findings were compared between patients with and without viremia and the risk factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not detected in the sera from 7 patients (group 1), but was detected in the sera from the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was significantly higher in group 2 than in group 1. The proportion of patients with active hepatitis was significantly higher in group 2. In group 2, new HCC often developed after the operation and four patients died of liver dysfunction. HCV viremia, high ALT activity, high concentration of total bilirubin, and liver cirrhosis were related to recurrence after the operation. Multivariate analysis indicated that HCV viremia and high ALT activity were independent risk factors for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened the outcome after the resection of HCC by causing new development of HCC and deterioration of liver function. In patients with HCV-related HCC, but without HCV viremia, satisfactory results can be expected after liver resection.

Aged↗
PubMed1999

[Prevalence of TT virus in patients with fulminant hepatic failure in Japan].

A novel virus(TTV) was isolated from patients with post-transfusion hepatitis of unknown etiology. We studied the prevalence of TTV in 26 patients with fulminant hepatic failure. Serum samples at admission from seven(27%) of the 26 patients were positive for TTV. TTV was also detected in 29(27%) of the 106 healthy blood donors. There were no differences in the positive rate between patients with fulminant hepatic failure and healthy blood donors. There were no differences in clinical findings, or duration from onset to coma in patients with and without TTV. However, the outcome of the patients with TTV was significant worse than those without. TTV may not cause severe hepatitis such as fulminant hepatic failure.

Adult↗
PubMed1999

Clinical usefulness of scintigraphy with 99mTc-galactosyl-human serum albumin for prognosis of cirrhosis of the liver.

UNLABELLED: Scintigraphy with 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is useful for evaluating hepatic functional reserve. We assessed the clinical usefulness of this technique, including its value in establishing a prognosis, in patients with cirrhosis of the liver. METHODS: Scintigraphy with 99mTc-GSA was performed in 10 healthy subjects, 42 patients with chronic hepatitis and 158 patients with cirrhosis. Computer acquisition of gamma camera data were started just before the injection of 99mTc-GSA. Time-activity curves for the heart and liver were generated from regions of interest (ROIs) for the heart and the entire liver. A receptor index was calculated by dividing the radioactivity of the liver ROI by that of the liver-plus-heart ROI 15 min after the injection. An index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. RESULTS: The median receptor index was lower in patients with cirrhosis than in patients with chronic hepatitis or in healthy subjects, and the median index of blood clearance was higher. The receptor index was significantly lower when a complication (varices, ascites) was present. The index of blood clearance was significantly higher when a complication (varices and ascites) was present. Correlation of the two indices with classic indicators for functional reserve was significant. On the basis of the receptor index, the patients with cirrhosis were divided into two groups of roughly equal size: group A, receptor index over 0.85, and group B, receptor index 0.85 or less. On the basis of the index of blood clearance, the patients with cirrhosis were divided into two groups of roughly equal size: group A, index of blood clearance < 0.70, and group B, index of blood clearance > or = 0.70. The cumulative survival rates were lower in group B than in group A. CONCLUSION: Scintigraphy with 99mTc-GSA is clinically useful, especially in establishing the prognosis of patients with cirrhosis of the liver.

Ascites↗
PubMed1999

Quantitative analysis and in situ localization of human telomerase RNA in chronic liver disease and hepatocellular carcinoma.

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. High levels of telomerase activity have been detected in most hepatocellular carcinoma (HCC) tissues; very weak telomerase activity is, however, detected in approximately half of nontumorous chronic liver disease tissues. The purpose of this study was to investigate the possible source of this weak telomerase activity in these tissues using quantitative competitive reverse transcription (RT)-polymerase chain reaction (PCR) and in situ RT-PCR. Competitive RT-PCR indicated that the relative amount of human telomerase RNA (hTR) was significantly higher in chronic hepatitis or liver cirrhosis compared with the normal liver (p < 0.005), and in HCC compared with the normal liver (p < 0.001) and with chronic hepatitis or liver cirrhosis (p < 0.0001). In the normal liver tissue, hTR was detected by in situ RT-PCR in occasional sinusoidal cells and nuclei of occasional hepatocytes. In tumor-free liver or tumor-bearing liver, hTR was detected in sinusoidal cells, infiltrating lymphocytes, occasional proliferative bile ductal epithelial cells, and the nuclei of occasional hepatocytes. In HCC, hTR was detected in nuclei of all HCC cells as an intense signal and in sinusoidal cells. These results indicate that the amount of hTR increases in the nuclei of hepatocytes during hepatocarcinogenesis, and that the cells associated with the weak telomerase activity in approximately half of the nontumorous chronic liver lesions are mainly migrating lymphocytes and sinusoidal cells.

Adult↗
PubMed1998

Sox1 directly regulates the gamma-crystallin genes and is essential for lens development in mice.

gamma-Crystallins are major structural components of the lens fiber cells in amphibians and mammals. Many dominant inherited cataracts in humans and mice have been shown to map within the gamma-crystallin gene cluster. Several transcription factors, including PAX6 and SOX proteins, have been suggested as candidates for crystallin gene regulation. Here we show that the targeted deletion of Sox1 in mice causes microphthalmia and cataract. Mutant lens fiber cells fail to elongate, probably as a result of an almost complete absence of gamma-crystallins. It appears that the direct interaction of the SOX1 protein with a promoter element conserved in all gamma-crystallin genes is responsible for their expression.

Animals↗
PubMed1998

Characteristics of patients with hepatitis C virus with and without GB virus C/hepatitis G virus co-infection and efficacy of interferon alfa.

GB virus C/hepatitis G virus (GBV-C/HGV) infection seems to be common among patients with hepatitis C virus (HCV) infection. We studied retrospectively the proportions of patients with GBV-C/HGV RNA and antibodies to the GBV-C/HGV second envelope protein (anti-E2) among 149 subjects with chronic hepatitis C who had received interferon alfa. The clinical characteristics of patients with GBV-C/HGV RNA or anti-E2 were examined, as was the efficacy of the treatment. Stored serum specimens were tested for GBV-C/HGV RNA by the reverse transcription polymerase chain reaction and for anti-E2 by an enzyme-linked immunosorbent assay. Of the 149 patients before therapy, 8 (5%) had GBV-C/HGV RNA only, 72 (48%) had anti-E2 only, and 4 (3%) had both. The mean age of patients with GBV-C/HGV RNA (some with anti-E2) was significantly less than that of patients with anti-E2 only. Results of laboratory and histological evaluations were not different depending on the presence of GBV-C/HGV RNA or anti-E2. The GBV-C/HGV RNA titer decreased during therapy in all 12 patients with GBV-C/HGV RNA; only 4, with a low titer before therapy and with anti-E2 detected at some time, had sustained clearance of GBV-C/HGV. Our results suggested that half of the patients with chronic hepatitis C had been exposed to GBV-C/HGV, but in almost all, the virus had been cleared; also, even chronic GBV-C/HGV infection did not affect the severity of the disease arising from HCV. Interferon alfa treatment was sometimes effective against GBV-C/HGV, and anti-E2 may be associated with clearance of GBV-C/HGV.

Adult↗
PubMed1998

Natural course of portal hemodynamics in patients with chronic liver diseases, evaluated by per-rectal portal scintigraphy with Tc-99m pertechnetate.

Portal circulation can be evaluated in a relatively noninvasive way by per-rectal portal scintigraphy. We used this method to evaluate portal hemodynamics in patients with chronic liver diseases and underlying hepatic viral infection; the patients did not need surgery or sclerotherapy, or refused it, so changes in the natural course were identified. A solution of Tc-99m pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were produced. The per-rectal portal shunt index was calculated from the curves. In a longitudinal study, 70 patients (9 with mild chronic hepatitis, 10 with moderate chronic hepatitis, 7 with severe chronic hepatitis, 22 with cirrhosis but without varices, and 22 with both cirrhosis and varices) were examined at least twice at intervals of 12-102 months (mean, 39 months). The shunt index was higher for more severe disorders, increasing in the order of mild chronic hepatitis, moderate chronic hepatitis, severe chronic hepatitis, cirrhosis without varices, and cirrhosis with varices. The mean annual changes in the mean shunt index were 1.0% in mild chronic hepatitis, 4.4% in moderate chronic hepatitis, 6.1% in severe chronic hepatitis, 10.7% in cirrhosis without varices, and 6.2% in cirrhosis and varices. Cirrhotic patients were arbitrarily divided into two groups of roughly equal size on the basis of the shunt index at the first examination. In those with a shunt index of 30% or more, the mean annual change was 4.7%. The patients with a shunt index of less than 30% had a mean annual change of 11.8%. Changes in the portal hemodynamics were not steady. The shunt index rose gradually as disease advanced from mild to moderate and to severe chronic hepatitis and cirrhosis of the liver, after which the index rose rapidly when varices developed, slowing later.

Cross-Sectional Studies↗
PubMed1998

Relationship between glutathione and polyamine metabolism after partial hepatectomy in alcohol-treated rats.

In a liver regeneration inhibiting model after partial hepatectomy in rats, we determined hepatic glutathione concentration and studied its relation with polyamine, an indicator of liver regeneration. Experiment 1: Male ODS rats and Wistar rats as control were maintained with vitamin C-deficient diets for 2 weeks. In the alcohol group, 3 g/kg of ethanol was administered orally 1 hr before partial hepatectomy. Experiment 2: Wistar rats were divided into four groups, according to the presence or absence of alcohol and vitamin E (VE), and a 6-week pair-feeding was done. As for partial hepatectomy, about 70% of the total liver was excised. As a result, in experiment 1, hepatic glutathione levels were significantly decreased by acute alcohol administration in both ODS and Wistar rats, and its level of alcohol administration group of ODS rats was the lowest. Hepatic ornithine decarboxylase activity and putrescine level 4 hr after partial hepatectomy showed almost a similar behavior, being the lowest in the alcohol administration group of ODS rats. In experiment 2, hepatic glutathione level showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. Hepatic ODC activity and putrescine level 4 hr after partial hepatectomy showed no influence by chronic alcohol administration, but was the lowest in the VE-deficient alcohol administration group. These results clarified that intrahepatic glutathione levels before partial hepatectomy were decreased in the models in which hepatic ODC activities after surgery were suppressed.

Animals↗
PubMed1998

Clinicopathological criteria for multicentricity of hepatocellular carcinoma and risk factors for such carcinogenesis.

Multicentric occurrence is an important characteristic of hepatocellular carcinoma. We evaluated clinicopathological criteria for multicentric hepatocellular carcinoma and identified risk factors for such carcinogenesis. Subjects were 251 consecutive patients undergoing liver resection for hepatocellular carcinoma. One kind of multicentric hepatocellular carcinoma had at least one tumor consisting of well-differentiated hepatocellular carcinoma, together with moderately or poorly differentiated hepatocellular carcinoma located in a separate region. The other kind had an area of well-differentiated component around hepatocellular carcinoma with less differentiation in all occurrences. The outcome of patients with tumors classified in this way was studied. Univariate and multivariate analyses were done to identify risk factors for multicentric hepatocellular carcinoma. The cumulative survival rate was significantly higher in patients with multicentric hepatocellular carcinoma than in patients with hepatocellular carcinoma associated with intrahepatic metastasis. Analysis by Cox's proportional hazard model showed that multicentricity was not a factor in the outcome. The risk of multicentric occurrence increases with progression of chronic liver disease. Univariate analysis showed hepatitis C virus marker and hepatitis B core antibody to be risk factors. By multivariate analysis, the odds ratio for multicentric occurrence in patients infected with hepatitis C virus and with serum hepatitis B virus core antibody compared with patients without either hepatitis C virus or hepatitis B virus was 10.86. This ratio in patients with hepatitis C virus alone was 4.30. These criteria for multicentric hepatocellular carcinoma seem to be clinically useful. Hepatitis C virus infection with or without former infection by hepatitis B virus is a strong risk factor for multicentric hepatocarcinogenesis.

Aged↗
PubMed1998

Effect of alcohol abuse on polyamine metabolism in hepatocellular carcinoma and noncancerous hepatic tissue.

BACKGROUND: Alcohol abuse is a risk factor for hepatocellular carcinoma (HCC) and the recurrence of HCC after resection. We therefore investigated polyamine metabolism, which is important in cell proliferation, HCC tissue, and noncancerous hepatic tissue. METHODS: In 30 patients who underwent liver resection for HCC, 13 patients had drunk 86 gm or more ethanol per day for at least 10 years (group 1), whereas the remaining 17 patients were nondrinkers or occasional drinkers (group 2). The control subjects were five patients who did not have liver disease or abuse alcohol. Tissue ornithine decarboxylase (ODC) activity and polyamine concentrations were measured. RESULTS: ODC activity in the HCC tissue was significantly higher in group 1 than in group 2. ODC activity in noncancerous tissue was significantly higher in group 1 than in group 2 and the control group. The ratio of spermidine/spermine in the HCC tissue was significantly higher in group 1 than in group 2. The ratio in noncancerous tissue was significantly higher in groups 1 and 2 than in the control group. CONCLUSIONS: Alcohol abuse affects polyamine metabolism, which influences the grade of malignancy of HCC. Hepatic tissue has greater potential for carcinogenesis in patients with chronic liver disease and alcohol abuse than in patients without them.

Aged↗
PubMed1997

Fiber-optic-based biomonitoring of benzene derivatives by recombinant E. coli bearing luciferase gene-fused TOL-plasmid immobilized on the fiber-optic end.

TOL plasmid in Pseudomonas putida mt-2 has a series of genes for the degradation of xylene, toluene, and their derivatives to pyruvate and acetaldehyde (or propionaldehyde). Two operons, i.e., upper operon and meta operon, play indispensable roles for the digestion of xylene derivatives: When XyIR protein recognizes xylene derivatives, another controlling gene, xyIS, is activated, which results in the activation of meta operon. Therefore, we have constructed a fusion gene between TOL plasmid and the firefly luciferase gene under the control of XyIR and the promoter of xyIS gene; i.e., by using fusions of the meta operon with promotorless luciferase expression vector from firefly, we have constructed and tested biomonitors for benzene derivatives. Bioluminescence specified by Escherichia coli (pTSN316), carrying xyIR and xyIS promoters, Ampr and luc, was measured in either a benzene derivative-saturated or o-methylbenzyl alcohol-dissolved medium both in the case of cell suspension and in the case of immobilized cell form. The utility of the biosensing system for monitoring in chemical plant drainage was demonstrated with samples supplemented with benzene derivatives. The xyIR-xyIS promoter-lux fusion carried by pTSN316 responded to a benzene-related chemical in sample solutions. Immobilization of the transformed E. coli, at one end of fiber optic, bearing firefly luciferase gene fused to TOL plasmid, has been demonstrated to fabricate a luminescent remote biomonitoring device for the protection of environmental deterioration. Due to the luminescent detection, the detection limits for benzene-related aromatics that are recognized by a binding protein (XyIR) were parts-per-million. We had already submitted a preliminary report concerning the possibility of environmental monitoring based on the above idea by using the transformed E. coli in a cell-suspended solution. This paper describes mainly a fiber-optic-based biomonitoring device for the protection of environmental deterioration.

Bacterial Proteins↗
PubMed1997

Prevalence of GBV-C and hepatitis G virus variants in patients with fulminant hepatic failure in Japan.

BACKGROUND/AIMS: Whether GB virus C and hepatitis G virus participate in fulminant hepatic failure is controversial. We studied the prevalence of the viral RNA in 48 patients. There were possible routes of infection, including blood transfusion, in 22 patients (group 1), and no risk factors in the other 26 (group 2). METHODS: We assayed serum viral RNA with reverse transcription and nested polymerase chain reactions. Serum was obtained at admission, and after transfusion in group 2. RESULTS: Five (10%) serum samples from group 1 at admission had viral RNA of the 5'-untranslated region, and three of these samples had viral RNA of the NS3/helicase region. All five patients had transfusions before sampling. Two (4%) samples from group 2 were positive by both tests only after transfusion. Of two patients, one with non-A-E fulminant hepatic failure survived. Her serum alanine aminotransferase did not increase further after transfusion, but did stay above the reference range during follow-up. The other patient, with infection with hepatitis B virus detected at admission, died. After transfusion, his alanine aminotransferase did not increase further. Partial nucleotide sequences of GB virus C and hepatitis G virus from three fulminant hepatic failure patients and five control patients with chronic hepatitis C were compared with published sequences. A viral variant causing fulminant hepatitis, suggested elsewhere, was not found, nor was all of a characteristic pattern of six mutations found elsewhere. CONCLUSIONS: GB virus C and hepatitis G virus may cause hepatitis, but probably not severe hepatitis such as fulminant hepatic failure.

Base Sequence↗
PubMed1997

Poor association of GBV-C viremia with hepatocellular carcinoma.

BACKGROUND/AIMS: The role of the hepatitis GB virus C in chronic liver disease is unclear. The clinical findings, results of laboratory tests, pathological findings, and outcome after liver resection for hepatocellular carcinoma in patients infected or not infected with GB virus C were compared. METHODS: Serum samples from 213 patients were tested for hepatitis B virus, hepatitis C virus, and GB virus C. Of the 213 patients, 159 had hepatitis C viral RNA or antibodies (group 1), seven had both hepatitis C viral RNA or antibodies and hepatitis B surface antigen (group 2), 25 had hepatitis B surface antigen (group 3), and 22 did not have hepatitis C viral RNA, hepatitis C antibodies, or hepatitis B surface antigen (group 4). RESULTS: GB virus C RNA was detected in 12 of the 213 patients. Of the 12 patients, 11 were in group 1 and one was in group 4. There were no patients with hepatocellular carcinoma associated with GB virus C RNA alone. In groups 1 and 4, there were no differences in clinical findings, results of laboratory tests, pathological findings, or outcome after surgery in patients with and without GB virus C RNA. CONCLUSIONS: These results indicate a poor association of GB virus C viremia with hepatocellular carcinoma. We did not find clinically significant interaction between hepatitis C virus and GB virus C.

Adult↗
PubMed1997

Detection by ligase chain reaction of precore mutant of hepatitis B virus.

The clinical diagnosis of infection with the most common precore mutant of hepatitis B virus (HBV), that with a point mutation from guanine to adenine at nucleotide 83 in the precore region, is important because the disease may progress rapidly despite interferon therapy. A practical method to detect this mutant is needed. With the ligase chain reaction (LCR), target DNA sequences can be amplified and single base mutations can be detected. We tried to detect mutant HBV by the LCR alone, but the limit of detection (10(9) copies per tube) was too high. To increase the sensitivity, we used the LCR on DNA already amplified by the polymerase chain reaction (PCR), and tested serum samples from 23 subjects with chronic HBV infection for mutant and wild-type HBV. As few as 10(2) copies per tube could be detected. The results corresponded with the results of nucleotide sequencing for 22 of the 23 patients. The ratio of clones of mutant and total viruses was estimated for each individual by PCR-coupled LCR. Seroconversion could be identified earlier in the illness by an increase in this ratio than by the decrease in HBeAg. We also tested serum samples from 11 patients with acute liver failure by PCR-coupled LCR. Mutant HBV was detected at a low ratio in all 4 patients with acute self-limited hepatitis (AH). Wild-type HBV coexisted with mutant HBV in 6 of 7 patients with fulminant hepatitis (FH), and the mean ratio of mutant to total HBV was significantly higher than that in AH. PCR-coupled LCR could be used to detect mutant HBV and to estimate the ratio of mutant to total viruses.

Adolescent↗