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Biomedical subjects

S Saitoh

Publications and source records attributed to S Saitoh.

At least 19 recordsLinked to original sources
PubMed2000

Incidence of primary cholangiocellular carcinoma of the liver in japanese patients with hepatitis C virus-related cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma. However, the risk factors for primary cholangiocellular carcinoma of the liver (PCC-L) have not been fully investigated. The authors determined the incidence of PCC-L in patients with HCV-related cirrhosis. METHODS: Between 1980 and 1997, the authors prospectively studied 600 consecutive patients for the appearance of PCC-L; these patients were positive for HCV and later developed cirrhosis. The follow-up period ranged from 0 to 18.5 years (median, 7.2 years). RESULTS: During the observation period, PCC-L developed in 14 patients (2.3%). Among these, 11 (1.8%) had cholangiocellular carcinomas and the other 3 (0.5%) had a combined type of hepatocellular and cholangiocellular carcinoma. Within the same period, hepatocellular carcinoma (HCC) developed in 206 patients (34.3%). The cumulative rates of newly diagnosed PCC-L were 1.6% at 5 years and 3.5% at 10 years, which was about 1000 times higher than the estimated incidence of PCC-L in the general population of Japan. PCC-L was treated by surgical resection in 3 patients who survived for > 3 years. However, the other 11 patients received palliative therapy or chemotherapy. The survival rates among PCC-L patients were 39.3%, 23. 6%, and 16.5% at the end of 1, 3, and 5 years, respectively, and were significantly lower than those of HCC (P = 0.0001). CONCLUSIONS: The results of this study show a relatively high incidence of PCC-L in patients with HCV-related cirrhosis, and also show that this type of liver cancer is associated with a relatively poor prognosis. These results indicate that HCV-related cirrhosis is a major risk factor for PCC-L in Japanese patients.

Adult↗
PubMed2000

Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome.

To examine the chromatin basis of imprinting in chromosome 15q11-q13, we have investigated the status of histone acetylation of the SNURF-SNRPN locus, which is a key imprinted gene locus in Prader-Willi syndrome (PWS). Chromatin immunoprecipitation (ChIP) studies revealed that the unmethylated CpG island of the active, paternally derived allele of SNURF-SNRPN was associated with acetylated histones, whereas the methylated maternally derived, inactive allele was specifically hypoacetylated. The body of the SNURF-SNRPN gene was associated with acetylated histones on both alleles. Furthermore, treatment of PWS cells with the DNA methyltransferase inhibitor 5-azadeoxycytidine (5-aza-dC) induced demethylation of the SNURF-SNRPN CpG island and restoration of gene expression on the maternal allele. The reactivation was associated with increased H4 acetylation but not with H3 acetylation at the SNURF-SNRPN CpG island. These findings indicate that (1) a significant role for histone deacetylation in gene silencing is associated with imprinting in 15q11-q13 and (2) silenced genes in PWS can be reactivated by drug treatment.

Acetylation↗
PubMed2000

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C.

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/ b ratio was 1-5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5-10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis.

Adult↗
PubMed2000

Hepatic vascular side effects of styrene maleic acid neocarzinostatin in the treatment of hepatocellular carcinoma.

Styrene-maleic acid neocarzinostatin (SMANCS) sometimes causes hepatic vascular side effects, including arterial stricture, obstruction, and arterio-portal shunt. A total of 128 intra-arterial SMANCS injection treatments, performed for 89 patients with hepatocellular carcinoma, were analyzed to determine the relationship between angiographic findings and subsequent hepatic vascular injuries. After SMANCS therapy, hepatic arterial stricture or obstruction occurred in 5 patients (5/128; 3.9%), arterio-portal shunting in 12 (12/128; 9.4%), liver shrinkage in 4 (4/128; 3.1%), and cholangitis or biloma in 2 (2/128; 1.6%). Among 23 patients whose plain abdominal X-ray films just after SMANCS injection showed Lipiodol retention in the hepatic artery, 5 patients developed arterial obstruction, 10 developed arterio-portal shunt, and 2, cholangitis or biloma. Among 26 patients with Lipiodol retention in the portal vein, 4 developed hepatic lobe atrophy with aggravation of liver function. Among 3 patients with Lipiodol retention in both the hepatic artery and the portal vein, 1 developed arterio-portal shunt. In 76 treatments without excessive Lipiodol retention, only 1 of the patients developed arterio-portal shunt. Excessive retention of Lipiodol in hepatic vascular beds just after SMANCS therapy was significantly associated with future vascular side effects (22/52 vs 1/76; P < 0.0001). Lipiodol retention in arteries just after SMANCS injection was closely associated with subsequent arterial obstruction or arterio-portal shunt, and Lipiodol retention in the portal vein was related to subsequent hepatic lobe atrophy.

Adult↗
PubMed2000

LAT is essential for Fc(epsilon)RI-mediated mast cell activation.

The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc(epsilon)RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc(epsilon)RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma1, and PLC-gamma2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc(epsilon)RI cross-linking. These results show that LAT plays a critical role in Fc(epsilon)RI-mediated signaling in mast cells.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Relationship between blood pressure level and mortality rate: an 18-year study conducted in two rural communities in Japan.

BACKGROUND: There have been very few studies on life prognosis of cardiovascular disease according to blood pressure stratification in the Japanese. Therefore, in Japan, although treatment of hypertension is possible, albeit at times difficult, due to the availability of various antihypertensive medications, the appropriate time at which treatment should be started remains a problem. OBJECTIVE: To investigate the long-term prognosis of cardiovascular disease in the Japanese general population according to blood pressure stratification in the Japanese. DESIGN: A community-based prospective cohort study of 1996 men and women between the ages of 40 and 64 years at the baseline examination was conducted over an 18-year period. Information on death was obtained from local public health nurses and death certificates. The causes of death were clarified by questionnaires sent to doctors in the hospital in which the deceased was hospitalized, and the causes of death were analysed in each blood pressure category at baseline examination. RESULTS: Mortality from cardiovascular disease increased with increases in the level of blood pressure and was significantly higher in > or = 140 mmHg group in systolic blood pressure and > or = 90 mmHg group in diastolic blood pressure, adjusted for age, sex and other cardiovascular risk factors in the Japanese general population. However, mortality risk from cardiovascular disease did not have a J-shaped relationship with systolic and diastolic blood pressure. CONCLUSION: We conclude that the optimum time for starting treatment in Japanese people is when blood pressure is 140/90 mmHg or less.

Adult↗
PubMed2000

Identification and expression of a Mycoplasma gallisepticum surface antigen recognized by a monoclonal antibody capable of inhibiting both growth and metabolism.

In order to identify antigenic proteins of Mycoplasma gallisepticum, monoclonal antibodies (MAbs) against virulent M. gallisepticum R strain were produced in mice. MAb 35A6 was selected for its abilities to inhibit both growth and metabolism of M. gallisepticum in vitro. The MAb recognized a membrane protein with an apparent molecular mass of 120 kDa. The corresponding gene, designated the mgc3 gene, was cloned from an M. gallisepticum genomic DNA expression library and sequenced. The mgc3 gene is a homologue of the ORF6 gene encoding 130-kDa protein in the P1 operon of M. pneumoniae and is localized downstream of the mgc1 gene, a homologue of the P1 gene. To assess the characteristics of MGC3 protein, all 10 TGA codons in the mgc3 gene, which encode a tryptophan in the Mycoplasma species, were replaced with TGG codons, and recombinant fowlpox viruses (FPV) harboring the altered mgc3 gene were constructed. One of the recombinant FPVs was improved to express MGC3 protein on the cell surface in which the signal peptide of MGC3 protein was replaced with one from Marek's disease virus gB. These results should provide the impetus to develop a vaccine based on MGC3 protein which can induce antibodies with both growth inhibition and metabolic-inhibition activities using a recombinant FPV.

Amino Acid Sequence↗
PubMed2000

Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism.

Bone metabolism is strongly influenced by heredity and environmental factors. To investigate interaction of the effects between vitamin D receptor polymorphism by Fok I and resistance exercise training on bone metabolism, young male subjects with FF genotype (F, n = 10) and Ff or ff genotypes (f, n = 10) followed 1 mo of weight training, and changes in bone metabolism were compared. An additional 14 subjects served as a sedentary control. Biomarkers of bone formation, bone-specific alkaline phosphatase, and osteocalcin were significantly increased by training in both F and f groups. 1, 25-Dihydroxyvitamin D(3), known to upregulate bone formation, was also increased by the training in the f but not in the F group. Bone resorption assessed by cross-linked NH(2)-terminal telopeptide of type I collagen was significantly suppressed by the training, and the decrease in F was greater and longer lasting than that in f group. In conclusion, stimulation of bone formation and suppression of bone resorption occurred within 1 mo in young men. Despite a significant increase in 1,25-dihydroxyvitamin D(3) in the f group but not in the F group, the response of bone metabolism to the training in the F was similar to or greater than that in f group, suggesting a functional difference between vitamin D receptor genotypes f and F.

Adult↗
PubMed1999

Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12.

Although tumor-specific T lymphocytes recognize tumor-associated antigens (TAA) present on their cell surface via major histocompatibility complex (MHC) molecules, T cells require other activating signals. These are provided by costimulatory molecules, including B7-1 (CD80), B7-2 (CD86) and intercellular adhesive molecule 1 (ICAM-1; CD54). Transfecting mouse tumor cell lines with the B7 gene can lead to primary tumor rejection and the establishment of protective immunity. However, some studies have shown that the B7 effect upon T-cell-dependent tumor immunity is limited. Therefore, we examined the antitumor effects of recombinant interleukin 12 (IL-12) and genetically engineered glioma cells expressing B7-1 or both B7-1 and ICAM-1. Vaccination of mice with B7-1-expressing tumor cells substantially inhibited the growth of subcutaneously inoculated gliomas but not those located in the brain. Vaccination with B7-1-expressing tumor cells and systemic recombinant IL-12 (rIL-12) was more effective than either B7-1-expressing tumor cells or rIL-12 alone. Our murine brain tumor model also showed that vaccination with tumor cells expressing both B7-1 and ICAM-1 combined with rIL-12 prolonged survival. We have demonstrated the therapeutic potential of vaccination with rIL-12 and tumor cells expressing both B7-1 and ICAM-1 in the control of glioma growth.

Animals↗
PubMed1999

Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation.

High-fidelity chromosome transmission is fundamental in controlling the quality of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister centromere-connecting proteins, Mis6 and Mis12, are required for correct spindle morphogenesis, determining metaphase spindle length. Thirty-five to sixty percent extension of metaphase spindle length takes place in mis6 and mis12 mutants. This may be due to incorrect spindle morphogenesis containing impaired sister centromeres or force unbalance between pulling by the linked sister kinetochores and kinetochore-independent pushing. The mutant spindle fully extends in anaphase, although it is accompanied by drastic missegregation by aberrant sister centromere separation. Hence, metaphase spindle length may be crucial for segregation fidelity. Suppressors of mis12 partly restore normal metaphase spindle length. In mis4 that is defective in sister chromatid cohesion, metaphase spindle length is also long, but anaphase spindle extension is blocked, probably due to the activated spindle checkpoint. Extensive missegregation is caused in mis12 only when Mis12 is inactivated from the previous M through to the following M, an effective way to avoid missegregation in the cell cycle. Mis12 has conserved homologs in budding yeast and filamentous fungi.

Amino Acid Sequence↗
PubMed1999

An imprinted, mammalian bicistronic transcript encodes two independent proteins.

Polycistronic transcripts are common in prokaryotes but rare in eukaryotes. Phylogenetic analysis of the SNRPN (SmN) mRNA in five eutherian mammals reveals a second highly conserved coding sequence, termed SNURF (SNRPN upstream reading frame). The vast majority of nucleotide substitutions in SNURF occur in the wobble codon position, providing strong evolutionary evidence for selection for protein-coding function. Because SNURF-SNRPN maps to human chromosome 15q11-q13 and is paternally expressed, each cistron is a candidate for a role in the imprinted Prader-Willi syndrome (PWS) and PWS mouse models. SNURF encodes a highly basic 71-aa protein that is nuclear-localized (as is SmN). Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain. Whereas some human tissues express a minor SNURF-only transcript, mouse tissues express only the bicistronic Snurf-Snrpn transcript. We show that both SNURF and SNRPN are translated in normal, but not PWS, human, and mouse tissues and cell lines. These findings identify SNURF as a protein that is produced along with SmN from a bicistronic transcript; polycistronic mRNAs therefore are encoded in mammalian genomes where they may form functional operons.

Amino Acid Sequence↗
PubMed1999

Specific IgG to gelatin in children with systemic immediate- and nonimmediate-type reactions to measles, mumps and rubella vaccines.

We examined anti-gelatin IgG in sera of children who suffered from systemic adverse reactions upon immunization with gelatin-containing live virus vaccines. In the group of 30 children who had immediate-type reactions and anti-gelatin IgE, 30 (100%) had anti-gelatin IgG and 29 (96%) had anti-gelatin IgG4. In another group of 75 children who had nonimmediate-type reactions and no anti-gelatin IgE, 22 (29%) had anti-gelatin IgG and six (8%) had IgG4. The IgG positivity well correlated with the lymphocyte proliferation assay positivity. In contrast, as a negative control, all 24 children who had no allergic reaction to live virus vaccines had no anti-gelatin IgG and IgG4. The results suggest that immune-response to gelatin may play a role in the pathogenesis of systemic nonimmediate-type reactions to the live virus vaccines.

Animals↗
PubMed1999

Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system.

Interleukin 12 (IL-12) exhibits anti-tumor activity in a variety of laboratory models. Although IL-12 itself activates strong anti-tumor activity, the combination of vaccine therapy with IL-2-transduced tumor cells and systemic rIL-12 has been shown to cure tumor-bearing mice more effectively than either rIL-12 or IL-2-transduced tumor vaccines alone. In the present study, regression of brain tumors established in naive mice was obtained by combined administration of an intratumoral injection of a single dose of IL-2-producing glioma cells (SR/IL-2 cells) and recombinant IL-12. Intraperitoneal rIL-12 administration substantially delayed the growth of s.c. inoculated gliomas, but not of gliomas located in the brain. Although vaccination with SR/IL-2 cells alone was not effective against s.c. inoculated gliomas, the combination therapy of vaccination with irradiated SR/IL-2 cells and systemic rIL-12 was more effective than rIL-12 alone. In our brain-tumor model, intratumoral administration of irradiated SR/IL-2 cells and of rIL-12 remarkably prolonged survival as compared with untreated mice. Efficacy was reduced when studies were performed in mice depleted of CD8+ cells or NK cells. Mice cured of their intracerebral tumors by combined administration of SR/IL-2 cells and rIL-12 demonstrated protective immunity upon rechallenge. In summary, the therapeutic potential for control of tumor growth by intratumoral administration of IL-2-producing glioma cells and rIL-12 may be useful in the development of treatment for patients with glioma.

Animals↗
PubMed1999

Fluctuations of hepatitis C virus load are not related to amino acid substitutions in hypervariable region 1 and interferon sensitivity determining region.

Hepatitis C virus (HCV) load is one of the most important predictive factors of response to interferon treatment. However, little is known about the mode and determinants of viremia. The mode of viremia was investigated in 78 patients with chronic HCV genotype 1b infection during 1-2 years follow up. Virus load, determined by a branched chain DNA amplification assay, was stable in 73 of 78 (93.6%) patients, whereas 5 (6.4%) showed marked fluctuation (from undetectable level to more than 10 Meq/ml) in viral titer. To study the mechanisms mediating fluctuations in viral titer, amino acid sequences of two regions were examined; hypervariable region (HVR) 1 and the interferon sensitivity determining region (ISDR). Multiple amino acid substitutions were observed in HVR 1 but no relationship was evident between substitutions and virus titers. In contrast, no amino acid substitutions were observed in the ISDR in any patients with stable virus titer during a follow-up period of 12-24 months (7-24 samples) or in one patient who was observed for 15 years. Interestingly, multiple amino acid substitutions in the ISDR appeared in only two of the five patients with marked titer fluctuation, when the virus decreased markedly. Alanine aminotransferase levels in these five patients correlated with viral load. The data suggest that amino acid substitutions in HVR1 and ISDR are not essential for changes in viral titer. Possible mechanisms of fluctuations of viral titer and amino acid substitutions in the ISDR accompanying marked reductions in viral load are discussed.

Alanine Transaminase↗
PubMed1999

Long-term result of arterial grafts interposed for arterial defects using the telescoping anastomotic technique: histological and angiographic study.

The arterial grafting model for arterial defects provides an ideal environment for the microvascular telescoping anastomosis because tension of the repaired vessel is maintained low and deformities of the inserted vessel end is minimal due to the thick arterial wall. The left femoral artery was grafted in 46 rats into the defect created in the right femoral artery using the telescoping anastomotic technique at both the proximal and distal anastomoses. The grafts were seen histologically and angiographically 3 to 4 months postoperatively in order to fairly evaluate the telescoping anastomosis in terms of long-term patency, stenosis, and changes in the outer and inner walls at the anastomosis. All arterial grafts were patent 3 to 4 months postoperatively and there were no aneurysms at the anastomoses. Enlargement of the graft diameter was minimal. The rate of stenosis at the anastomosis was smaller than that 1-day postoperatively. Even though the thick arterial wall was initially inserted and the intimal hyperplasia was still present at the anastomosis 3 to 4 months postoperatively, the long-term stenosis was relatively mild due to the atrophy in the overlapped walls.

Anastomosis, Surgical↗