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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

At least 19 recordsLinked to original sources
PubMed1998

Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7.

cDNAs for three human Wnt receptors, Frizzled-1 (FZD1), Frizzled-2 (FZD2), and Frizzled-7 (FZD7), have now been cloned and characterized. The FZD1, FZD2, and FZD7 genes encode the 647-, 565-, and 574-amino-acid proteins, respectively. FZD1, FZD2, and FZD7 share a common structure consisting of seven transmembrane domains, a cysteine-rich domain in the N-terminal extracellular region, and the C-terminal Ser/Thr-Xxx-Val motif. Relatively large amounts of FZD 1 mRNA, 4.5 kb in size, were detected in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary and in fetal lung and kidney. FZD2 mRNAs 4.0 and 2.4 kb in size were detected in adult heart, fetal brain, lung, and kidney. The level of FZD7 mRNAs 5.0 and 4.0 kb in size was high in adult skeletal muscle and fetal kidney, followed by fetal lung, adult heart, brain, and placenta. The FZD1 and FZD7 genes have been mapped to human chromosome 7q21 and 2q33, respectively.

Adult↗
PubMed1998

Full-length complementary DNA of hepatitis C virus genome from an infectious blood sample.

We constructed a full-length complementary DNA (cDNA) clone of hepatitis C virus (HCV) from a blood sample of an HCV carrier. The blood from the carrier was eventually transfused to a patient who later developed typical posttransfusion hepatitis C. It was also shown to be infectious to chimpanzees. We obtained 12 overlapping cDNA fragments altogether, covering the entire HCV genome. By subcloning and sequencing, clones considered to constitute the major population were selected. We could also detect 98 base pairs of extra sequences at the 3' end of the genome. After confirming the overlapping sequences, we combined the fragments to make a full-length cDNA. The HCV population in the donor was heterogeneous, as determined by their nucleotide sequences of the hypervariable region in envelope protein, but a few virus clones were selected in the recipient after transmission. The similar convergence of the virus population was previously observed when the same blood sample was injected into a chimpanzee. Interestingly, virus clones isolated during the acute phase in the recipient and the chimpanzee had sequences in the hypervariable region identical to that of the full-length cDNA clone. The full-length cDNA clone of HCV constructed in this study may originate from infectious virus clones.

Amino Acid Sequence↗
PubMed1998

Dedifferentiated chordoma: a case report.

Dedifferentiated chordoma, i.e. chordoma with a sarcomatous component, is a rare bone tumor. This case report is of a dedifferentiated chordoma in the sacrococcygeal region in a 50-year-old male. The patient was initially diagnosed as having a leiomyosarcoma at the first medical consultation, but after the tumor recurred it was proven to be a dedifferentiated chordoma. The primary tumor, which measured 7 x 5 cm, was located in front of the sacrum so as to compress the rectum forward. The resected specimen showed histological features of chordoma, but the presence in some parts of the tumor of spindle-shaped epithelial cells led to a misdiagnosis of leiomyosarcoma. Thirty-six months later, a local recurrent tumor measuring 24 x 17 cm was identified and promptly resected. The recurrent tumor showed features of pleomorphic cell sarcoma mimicking malignant fibrous histiocytoma. In the pleomorphic sarcomatous area, many mitotic figures were seen, and the MIB-1 labeling index was greater than 40%, which was higher than that of the conventional chordoma area. From histological and immunohistochemical examination, the resected tumor was proven to be a dedifferentiated chordoma. This case highlights the importance of careful study of suspected chordoma to allow early identification of sarcomatous components. When we encounter a chordoma with a spindled epithelial component, we need to distinguish this tumor from a dedifferentiated chordoma and other spindle cell sarcomas such as leiomyosarcoma.

Bone Neoplasms↗
PubMed1998

Correlation of a polymorphism in the interleukin-1 receptor antagonist gene with hepatic fibrosis in Japanese alcoholics.

The aim of this study was to determine whether there is any association between interleukin-1 receptor antagonist (IL1-Ra) genotype and alcoholic liver disease. The IL1-Ra genotype was assessed in 102 Japanese male alcoholic liver disease patients and 46 healthy subjects by polymerase chain reaction with leukocyte DNA. The distribution of IL1-Ra genotype and the allelic frequencies in Japanese healthy subjects are both significantly different from that previously reported in Caucasians (A1/A1 genotype: 95.7% in Japanese vs. 54.0% in Caucasians, p < 0.001; A1 allele: 97.8% vs. 73.4%, p < 0.001). The frequency of A1 heterozygotes tended to be higher in Japanese alcoholics with fibrosis, compared with those without fibrosis (14.9% vs. 2.9%). Furthermore, within the fibrotic groups, cumulative alcohol intake was significantly lower in A1 heterozygotes than in the A1 homozygotes (877 +/- 118 kg vs. 1369 +/- 90 kg,p < 0.05). In conclusion, a genetic polymorphism in the IL1-Ra gene may influence the risk of developing hepatic fibrosis in Japanese alcoholics. The same study should be conducted in Caucasian patients having more frequency of IL1-Ra A1 heterozygotes.

Adult↗
PubMed1998

Thromboembolic complication in atrial fibrillation in a long-term follow-up--the relationship with underlying disease, type of atrial fibrillation, and antithrombotic therapy.

The incidence of thromboembolic complications among 288 patients with atrial fibrillation (AF) who were followed up during an average period of 7.2 years was examined retrospectively. The annual incidence of thromboembolic complications was 1.6% in total, 1.7% in valvular heart disease (n=128), and 2.1% in non-valvular heart disease (n=117). No thromboembolism occurred in lone AF (n=43), defined as the complete absence of any underlying disease. The type of AF before embolic attack was chronic in 26 cases and paroxysmal in 6 cases. The cardiac rhythm at the time of the embolic attack was AF, except in 2 cases in which ECG was not recorded. In all patients with thromboembolic complications who were receiving antithrombotic therapy during the follow-up, the anticoagulant effect just before the embolic attack was found to be insufficient. Major bleeding was not observed in the patients receiving antithrombotic therapy. Thromboembolism in AF in long-term follow-up tends to occur more frequently in patients with underlying heart disease and in those with chronic AF compared rather than paroxysmal AF; it rarely occurs in lone AF. We should not hesitate to administer sufficient anticoagulant therapy in AF patients who are at high risk of developing thromboembolic complications.

Adult↗
PubMed1998

[Outcome of TAE for hepatocellular carcinoma: comparative study of SMANCS-TAE and non-SMANCS/LpTAE].

The therapeutic effectiveness of transcatheter arterial embolization (TAE) with intraarterial infusion of SMANCS/lipiodol mixture was retrospectively compared to TAE with intraarterial infusion of epirubicin/lipiodol mixture in initial treatment of 54 patients with unresected hepatocellular carcinoma. The therapeutic effects were evaluated by the rate of tumor necrosis after the initial procedure and the cumulative survival rate. Eighteen patients were treated with SMANCS, and 36 patients were treated with epirubicin. There was no significant difference in patient background between the two groups; the hepatic functional reserve was not seriously disturbed in most of the patients, and multiple hepatic lesions were seen in half the patients. Complete tumor necrosis assessed by the imaging of dynamic CT one month after TAE was seen in approximately 40% of the cases in each group. Local recurrence was seen in half the patients after assessment of complete tumor necrosis within one year in both groups. There was no significant difference in survival period. There was also no significant difference of the frequency and degree of the side effects. In conclusion, no distinct difference of outcome was found in the two groups in this comparative study. Further studies in many cases over a longer period will be needed to elucidate the effects of SMANCS in TAE.

Aged↗
PubMed1997

Association between frequency of amino acid changes in core region of hepatitis B virus (HBV) and the presence of precore mutation in Japanese HBV carriers.

To elucidate the relationship between the frequency of core mutations and precore mutation of hepatitis B virus (HBV) in Japanese HBV carriers, we investigated the nucleotide sequence of the precore/core region of HBV in 26 Japanese HBV carriers [15 who were HBe antigen-negative (HBeAg-) and 11 who were HBeAg-positive (HBeAg+)]. The number of amino acid changes (5.9 +/- 3.8) in the core region of HBV in HBeAg-carriers was significantly greater than that in the HBeAg+ carriers (1.5 +/- 1.0; P < 0.005). The precore stop codon mutation was found in 93.3% of HBeAg-negative HBV carriers, while no precore mutation was found in the HBeAg-positive HBV carriers, suggesting that the frequency of core mutations may be associated with the presence of the precore stop codon mutation. However, there was no significant difference in the frequency of amino acid changes among HBeAg-HBV carriers. The mean number of core amino acid changes of liver cirrhosis patients, chronic active hepatitis patients, chronic persistent hepatitis patients, and asymptomatic carriers were 2.7 +/- 1.5, 6.0 +/- 2.2, 4.7 +/- 1.2, and 8.4 +/- 5.3, respectively. We detected hot spots for core mutations, which showed characteristic localizations and specific substitutions: Gly-87, Leu-97, and Thr-130 were detected exclusively in patients with chronic liver disease with or without HBeAg. To address further the relationship between frequency of core mutations and the presence of the precore stop codon mutation, we investigated the precore/core nucleotide sequence serially along with seroconversion in three patients with chronic hepatitis B in whom the hepatitis either became inactive or remained active after the seroconversion. Emergence of the precore stop codon mutation and a significant increase in core amino-acid changes after seroconversion were noted in all three patients. Our results suggest a close association between the frequency of core amino acid changes and the presence of the precore stop codon mutation; some characteristic core mutations may be associated with the clinical course of chronic hepatitis B in Japanese patients.

Adult↗
PubMed1997

Induction of autoimmune-like hepatic and ductal lesions by administration of lipopolysaccharide in mice undergoing graft-versus-host reaction across MHC class I difference.

In this paper, we examined the induction of autoimmune-like histologic changes in the liver and other organs of mice undergoing graft-versus-host reaction (GVHR) with MHC class I disparity by the administration of bacterial lipopolysaccharide (LPS), on the assumption that stimulation with LPS could be an exacerbating factor. Spleen cells of C57BL/6 (B6) mice were injected twice into (B6 x bml) F1 recipient mice at an interval of 7 days to induce MHC class I GVHR and then challenged with 1 microg of LPS intravenously on the next day of the cell transfer. The hepatic lesions of the group of MHC class I GVHR mice challenged with LPS showed marked cellular infiltration at the portal area and focal necrosis was observed in the hepatic lobule. The major infiltrating cells were CD8+, and others including CD4+ cells being of minor populations. In addition, ductal lesions in extrahepatic organs, including the pancreas and salivary glands also showed marked cellular infiltration. Thus, we have demonstrated that LPS induced ductal lesions in mice with MHC class I disparity. CD8+ cells were detected at the destructive hepatic lesions, which might be effector cells. These findings indicate that LPS might be one of the potential factors which augment autoimmune-like lesions.

Alanine Transaminase↗
PubMed1997

Present status of autoimmune hepatitis in Japan--correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis.

BACKGROUND/AIMS: A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS: Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS: The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Adolescent↗
PubMed1997

Clinical efficacy of lactulose in cirrhotic patients with and without subclinical hepatic encephalopathy.

Seventy-five cirrhotic patients with hyperammonemia in the past or at the time of the study were randomly divided into two groups (treated with lactulose or nontreated) in 14 hospitals in Japan. Thirty-six cirrhotic patients were diagnosed as having subclinical hepatic encephalopathy (SHE), and 39 were diagnosed as non-SHE. SHE was diagnosed when the results of all three of the quantitative psychometric tests used (number connection test, and symbol digit and block design tests of the Wechsler adult intelligence scale [revised]) were abnormal as compared with age-matched normal values. The mean number of abnormal psychometric test results and the prevalence of SHE were used for a quantitative evaluation of the efficacy of the lactulose treatment. Twenty-two of the SHE patients were treated with lactulose (45 mL/d) for 8 weeks, and the other 14 SHE patients did not receive lactulose. In the SHE patients administered lactulose, the results of the quantitative psychometric evaluation were significantly improved at 4 and 8 weeks after the beginning of the lactulose administration. The SHE had disappeared in 10 (50%) of the 20 treated patients at week 8, but it persisted in 11 (85%) of the untreated 13 patients. We concluded that lactulose treatment in cirrhotic patients with SHE is effective with respect to psychometric tests.

Administration, Oral↗