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S Fujimori

Publications and source records attributed to S Fujimori.

At least 19 recordsLinked to original sources

Cytoprotection by pyruvate through an anti-oxidative mechanism in cultured rat calvarial osteoblasts.

Although we have previously shown drastic cell death by pyruvate deficiency in osteoblasts at the proliferative stage, the exact mechanism remains unclear so far. Cell survivability was significantly decreased in rat calvarial osteoblasts cultured for 0 to 3 days in vitro (DIV) following replacement of the eutrophic alpha-modified minimum essential medium (alpha-MEM) with Dulbecco's modified eagle medium (DMEM) for cultivation. The addition of pyruvate enriched in alpha-MEM, but not in MEM, entirely prevented cell death induced by the medium replacement throughout a culture period from 0 to 3 DIV. Both cysteine and reduced glutathione protected cell death in cells cultured for 3 DIV without significantly affecting that in cells cultured for 1 DIV, however, while none of lactate, acetate and insulin significantly prevented the cell death irrespective of the culture period up to 3 DIV. A marked increase was detected in intracellular reactive oxygen species (ROS) levels 4 h after the medium replacement. In osteoblasts cultured in alpha-MEM for 3 DIV, but not in those for 7 DIV, hydrogen peroxide (H2O2) markedly decreased cell survivability when exposed for 2 to 24 h. Furthermore, H2O2 was effective in significantly decreasing cell survivability in osteoblasts cultured in DMEM for 7 DIV. Pyruvate at 1 mM not only prevented cell death by H2O2, but also suppressed the generation of intracellular ROS in osteoblasts exposed to H2O2. These results suggest that pyruvate could be cytoprotective through a mechanism associated with the anti-oxidative property rather than an energy fuel in cultured rat calvarial osteoblasts.

Animals↗

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. METHODS: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E(2) and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. RESULTS: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1alpha and MIP-1beta, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE(2) and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE(2) and VEGF release in macrophages. Addition of exogenous PGE(2) reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. CONCLUSIONS: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

Adenoma↗

[Thoracoscopic resection for Mycobacterium avium complex].

We report 2 cases of thoracoscopic resection for patients with Mycobacterium avium complex (MAC). A 25-year-old female was referred to our hospital because of abnormal shadows in the right lower lung field on chest X-ray. Her chest computed tomography (CT) showed that the lesion was localized in the right lower lobe. She was given a diagnosis of MAC by polymerase chain reaction (PCR) of sputum. Thoracoscopic lobectomy was performed after chemotherapy for 10 months. A 64-year-old female was referred to our hospital because of hemoptysis. Bronchiectasis had been diagnosed in her since the age of 35 years, and then she was given a diagnosis of secondary MAC. Her chest CT showed bronchiectasis, and consolidations were localized in the superior segment of the right lower lobe. Then superior segmentectomy of the right lower lobe under video-assisted thoracoscopic surgery (VATS) was performed. It was reported that surgical intervention is indicated in patients with MAC, when persistent hemoptysis is seen or chemotherapy is ineffective. If the lesion is localized, lung resection under VATS may be a good option in selected patients.

Adult↗

On biased distribution of introns in various eukaryotes.

We conducted comprehensive analyses on intron positions in the Mus musculus genome by comparing genomic sequences in the GenBank database and cDNA sequences in the mouse cDNA library recently developed by Riken Genomic Sciences Center. Our results confirm that introns have a tendency to be located toward the 5' end of the gene. The same type of analysis was conducted in the coding region of seven eukaryotes (Saccharomyces cerevisiae, Plasmodium falciparum, Caenorhabditis elegans, Drosophila melanogaster, M. musculus, Homo sapiens, Arabidopsis thaliana). Introns in genes with a single intron have a locational bias toward the 5' end in all species except A. thaliana. We also measured the distance from the start codon to the position of the intron, and found that single introns prefer the location immediately after the start codon in S. cerevisiae and P. falciparum. We discuss three possible explanations for these findings: (1) they are the consequence of intron loss by reverse-transcriptase; (2) they are necessary to accommodate the function; and (3) they are concerned with the mechanism of pre-mRNA splicing.

Animals↗

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

BACKGROUND: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. METHODS: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. RESULTS: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. CONCLUSIONS: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.

Adenocarcinoma↗

Group III metabotropic glutamate receptors in rat cultured calvarial osteoblasts.

Reverse transcription polymerase chain reaction revealed expression of mRNAs for particular receptors for the central neurotransmitter l-glutamic acid (Glu) in primary cultures of rat calvarial osteoblastic cells under premature to mature states according to the duration of days in vitro. These included metabotropic Glu receptors (mGluR) such as mGluR4 and mGluR8, in addition to several ionotropic Glu receptor subunits including NR1 and NR2D. Expression of mRNAs was not detected with other mGluR and NR2A-C subunits irrespective of the maturity of cultured cells. The agonist for group III mGluR L-(+)-2-amino-4-phosphonobutyric acid significantly inhibited the forskolin-induced accumulation of cAMP in premature osteoblasts, which occurred in a manner sensitive to prevention by the group III mGluR antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine. These results suggest that Glu may at least in part play a role in mechanisms associated with cellular proliferation and/or differentiation through group III mGluR functionally expressed in rat calvarial osteoblastic cells.

1-Methyl-3-isobutylxanthine↗

A recurrent large Alu-mediated deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene associated with Lesch-Nyhan syndrome.

We identified the identical large genomic deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene in two Japanese patients with Lesch-Nyhan (LN) syndrome. This deletion spanned from an Alu sequence in the promoter region to another Alu-sequence in intron 1, a length of 2,969 base pairs including exon 1. In order to ask whether this deletion was a recurrent mutation, we developed a simple alternative method to determine the separate origin of the HPRT1 mutation of the patients as assessed with an apparent mtDNA polymorphism. Considering that an LN syndrome-causing mutation is not transmitted from patient to offspring as LN syndrome is a fatal disease in childhood and that mtDNA is maternally inherited, HPRT1 mutations and mtDNA would be co-transmitted from carrier mother to offspring since both appeared in females. Two bases were different in the hypervariable region I of the mtDNA between the two patients, indicating the separate origin of their mtDNA over at least several thousand years as calculated based on the molecular evolution rate in this region. We thus conclude that the identical deletion found in HPRT1 of the two patients was derived from recurrent events of genomic recombination. Given that the same Alu-mediated deletion of HPRT1 has not been reported among somatic mutations at the same locus, this region of the HPRT1 gene flanked by Alu-sequences is likely a mutational hot spot in the germline but not in somatic cells. In addition, we also report novel LN-syndrome-conferring mutations in intron 6 (IVS6+1G --> C) and intron 8 (IVS7-9T --> G) that resulted in exclusions of exon 6 and exon 8, respectively.

Alternative Splicing↗

The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol levels.

The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which originates mainly in the diet, is used in Japan as a new marker for glycemia. To evaluate the potential interference of 1, 5-AG measurements by traditional Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of concentrated dosage forms of Kampo using high performance liquid chromatography (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g dry weight), contained large amounts of 1,5-AG. Six others contained small amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2 diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9 to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking Kampo which contains Polygalae radix.

Aged↗

Mean corpuscular volume may be a useful index of risk for colorectal adenoma in middle-aged Japanese men.

OBJECTIVE: It has been reported that alcohol intake and folate deficiency are associated with an increased risk of colorectal adenomas and carcinomas. Mean corpuscular volume (MCV) of red blood cells has been reported to be increased in these conditions. The purpose of this study was to assess the association between MCV and risk of colorectal adenoma. METHODS: The subjects were 497 middle-aged (45-65 yr old) men who underwent both barium enema examination and total colonoscopy. The subjects answered a questionnaire regarding their alcohol consumption history, and their blood samples were analyzed. The subjects were divided into four groups three times: with or without alcoholism, and with or without adenoma according to alcohol intake, and according to the MCV value. Various variables were compared among the groups, and the odds ratios of adenoma were calculated. RESULTS: The MCV was higher in the alcoholic group than in the nonalcoholic group (p < 0.01) and in patients with adenoma than in those without adenoma (p < 0.0001). When the subjects were stratified by alcohol intake, the MCV value had a higher significant difference than alcohol intake, between patients with adenoma and those without adenoma. As for the MCV value, the odds ratio (95% confidence interval) of adenoma was 1.00 (referent); (<92), 1.20 (0.71-1.69); (> or =92 but <95), 2.61 (2.07-3.15); (> or =95 but <98); and 3.62 (2.99-4.25); (> or =98). CONCLUSION: A high MCV value may be used as a simple index of the risk of colorectal adenomas, regardless of alcohol consumption.

Adenoma↗

Proliferation and differentiation of bone marrow cells on titanium plates treated with a wire-type electrical discharge machine.

For successful dental implants, it is necessary to obtain satisfactory osteointegration at the site of both the cortical and trabecular bones in the jaw. Bone marrow stromal cells differentiate into osteoblast-lineage cells and have an important role in bone remodeling. In this experiment, the responsiveness of bone marrow cells to a titanium plate with a rough surface was compared with that of a titanium plate with a smooth surface. The rough surface was created by treating with a wire-type electrical discharge machine, and the smooth plate was produced by polishing with 1.500-grade emery paper. The results indicated that, though bone marrow cells proliferated on both plates, the proliferation pattern and cell growing time on the plates were different. While the cells on the smooth plate proliferated along the grooves produced by polishing, the cells on the rough plate proliferated randomly and more rapidly. As bone marrow cells consisted of heterogeneous cell populations involving hematopoietic cells, we collected bone marrow mesenchymal stromal cells that proliferated on plastic dishes and studied the proliferation and differentiation of these cells. Stromal cells on the rough plate more actively proliferated than those on the smooth plate. In long-term culture, the cells on the rough plate showed higher alkaline phosphatase activity and produced cell nodules. The cells on the smooth plate were stripped off the plate without nodule formation. These results indicated that bone marrow stromal cells on the rough plate could more rapidly proliferate and differentiate into osteoblast-lineage cells compared with those on the smooth plate.

Animals↗

Risk of colorectal cancer in patients with hematologic disease.

BACKGROUND AND AIMS: A relatively large number of patients with multiple myeloma have been reported to develop a secondary malignancy such as cancer of the breast, biliary system or bowel. METHODS: A retrospective study was perfomed in 734 patients with hematologic disease diagnosed at Nippon Medical School Hospital between May 1984 and September 1994 to determine the incidence of colorectal cancer in these patients based on a history review, colonoscopic findings, and surgical or autopsy data. RESULTS: Of the 734 patients, 14 (1.9%) had colorectal cancer; two of 11 patients (18.2%) had pure red cell aplasia; two of 25 patients (8%) had multiple myeloma; and three of 46 patients (6.5%) had aplastic anemia. Patients with pure red cell aplasia, multiple myeloma or aplastic anemia had colorectal cancer at a significantly higher rate compared to those with leukemia (P< 0.005, P< 0.02, P< 0.01, respectively). CONCLUSIONS: It is possible that a relatively large number of patients with pure red cell aplasia, multiple myeloma or aplastic anemia will develop a colorectal cancer.

Aged↗

Pharmacokinetics of 9alpha-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate.

Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9alpha-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 microg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity.

Administration, Oral↗

Superficial blood flow, blood volume, and blood velocity in colorectal tubular adenomas and adenocarcinomas.

To clarify differences in the vasculature of benign and malignant colorectal tumors, we compared blood flow (which has been examined in previous studies) as well as blood volume and blood velocity in two types of human colorectal tumors. We measured blood flow and blood volume with an endoscopic laser-Doppler flowmeter in the lesions and the normal mucosa near the lesions of 79 tubular adenomas with mild dysplasia and 38 adenocarcinomas. Blood velocity was defined as blood flow per blood volume. The ratio of each value in the lesions to that in the neighboring normal mucosa was defined as the relative value, and the mean relative values in the two groups were compared. The relative blood flow was 1.89 +/- 0.64 in the tubular adenomas and 1.49 +/- 0.66 in the adenocarcinomas (P < 0.005), and the relative blood volume was 1.10 +/- 0.14 and 0.90 +/- 0.13, respectively (P < 0.001). The relative blood velocity was approximately 1.7 in both groups (NS). This study demonstrated that the superficial blood flow in adenocarcinomas is increased due to increased blood velocity, despite blood volume being decreased.

Adenocarcinoma↗