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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 433 records · Page 24Linked to original sources
PubMed1997

Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum.

Although sphingosine 1-phosphate (Sph-1-P) is reportedly involved in diverse cellular processes and the physiological roles of this bioactive sphingolipid have been strongly suggested, few studies have revealed the presence of Sph-1-P in human samples, including body fluids and cells, under physiological conditions. In this study, we identified Sph-1-P as a normal constituent of human plasma and serum. The Sph-1-P levels in plasma and serum were 191+/-79 and 484+/-82 pmol/ml (mean+/-SD, n=8), respectively. Furthermore, when Sph-1-P was measured in paired plasma and serum samples obtained from 6 healthy adults, the serum Sph-1-P/plasma Sph-1-P ratio was found to be 2.65+/-1.26 (mean+/-SD). It is most likely that the source of discharged Sph-1-P during blood clotting is platelets, because platelets abundantly store Sph-1-P compared with other blood cells, and release part of their stored Sph-1-P extracellularly upon stimulation. We also studied Sph-1-P-related metabolism in plasma. [3H]Sph was stable and not metabolized at all in plasma, but was rapidly incorporated into platelets and metabolized mainly to Sph-1-P in platelet-rich plasma. [3H]Sph-1-P was found to be unchanged in plasma, revealing that plasma does not contain the enzymes needed for Sph-1-P degradation. In summary, platelets can convert Sph into Sph-1-P, and are storage sites for the latter in the blood. In view of the diverse biological effects of Sph-1-P, the release of Sph-1-P from activated platelets may be involved in a variety of physiological and pathophysiological processes, including thrombosis, hemostasis, atherosclerosis and wound healing.

Blood Cells↗
PubMed1997

Index for predicting post-operative residual liver function by pre-operative dynamic liver SPET.

To predict residual liver function before hepatic resection, we devised a predictive index by combining clearance values with functional liver volume measured by liver dynamic single photon emission tomography (SPET). Forty-seven patients with liver disease underwent liver dynamic SPET with 99Tcm-Sn colloid before hepatic resection. There were no operation-related deaths. Three patients died from hepatic failure more than 1 month following the operation. Their predictive indices were 0.24, 0.33 and 0.34. When the predictive index was above 0.35, no patient had symptoms of hepatic failure or died. Our data suggest that when the predictive index is above 0.35, there is a low probability of hepatic failure after hepatectomy.

Adult↗
PubMed1997

A reversed-flow latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction.

We report a case using the latissimus dorsi musculocutaneous flap based on the serratus branch in primary shoulder reconstruction. The reversed flow of the serratus branch maintained the circulation of the flap following acute disruption of the thoracodorsal vessels. Although our case was unusual, the reversed-flow latissimus dorsi flap based on its serratus branch may add a useful option in some cases.

Adult↗
PubMed1997

The value of LYM-1 cells for examining vacuole formation and loss of cell viability induced by culture supernates of Helicobacter pylori.

Some strains of Helicobacter pylori are known to produce an extracellular cytotoxin that causes vacuolation in cultured mammalian cells. Screening for such strains makes use of HeLa cells which may not be sensitive enough to detect minimal changes. The aim of this study was to develop a more sensitive cell line. Vacuole formation was examined in HeLa cells, as well as four other cell lines established in this laboratory by ammonium chloride induction. Among five cell lines tested, LYM-1 cells were most sensitive for the detection of intracellular vacuolation with this agent. Loss of cell viability of LYM-1 and HeLa cells induced by H. pylori culture supernates was also examined: LYM-1 were more sensitive than HeLa cells. Cell death was not always accompanied by vacuole formation. This suggests that the mechanism whereby cell death occurs must be different from that for vacuole formation. LYM-1 cells may be useful when measuring vacuole formation and cell death of the cultured cells induced by culture supernates of clinical isolates of H. pylori.

Ammonium Chloride↗
PubMed1997

Evidence for transcriptional regulation of plastid photosynthesis genes in Arabidopsis thaliana roots.

Mechanisms underlying suppressed levels of transcripts for plastid photosynthesis genes in nongreen tissues such as roots and calli were analyzed in Arabidopsis thaliana, a plant suitable for further genetic dissection. A region encoding promoters of rbcL, the gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase/oxygenase, and the atpB/E operon for the beta and epsilon subunits of coupling factor one were cloned and sequenced. Transcripts for rbcL, atpB/E, and psbA, the gene for the D1 protein in the photosystem II reaction center, were barely detectable in roots of A. thaliana, whereas 16S rRNA was detected at a low level. The run-on transcription experiment revealed that expression of rbcL, atpB/E, and psbA was regulated at transcription. The copy number of plastid DNA in roots was one-fifth that in green leaves on the basis of total cellular DNA, suggesting that in the latter the DNA copy-number regulation also exists in plastid gene expression. Digestion of DNA with methyl-sensitive and -insensitive isoschizomeric endonucleases and subsequent polymerase chain reaction, as well as in vitro transcription of plastid DNAs with Escherichia coli RNA polymerase, resulted in no evidence of regulation by DNA modification. In spite of predominant suppression of expression of rbcL, atpB/E, and psbA at transcription in roots and calli, 16S rRNA levels were decreased because of low RNA stability.

Arabidopsis↗
PubMed1997

Contiguous four-guanosine sequence in c-myc antisense phosphorothioate oligonucleotides inhibits cell growth on human lung cancer cells: possible involvement of cell adhesion inhibition.

A contiguous four-guanosine (4G) sequence in c-myc antisense phosphorothioate oligonucleotides caused an antiproliferative effect in smooth muscle cells. To investigate the antiproliferative effect of c-myc antisense oligonucleotides on human lung cancer cell lines, we synthesized oligonucleotides of various lengths and sequences, focusing on the contiguous four-guanosine (4G) sequence. While a c-myc antisense oligonucleotide (20AS1 (4G)) targeted to the translation initiation codon of c-myc mRNA inhibited cell growth of A549 cells by 69% at 10 microM, a scrambled oligonucleotide (20SCR1 (4G)) containing the contiguous four-guanosine (4G) sequence also inhibited cell growth by 72% at the same dose. Although treatment with either 20AS1 (4G) or 20SCR1 (4G) inhibited cell adhesion by 70% at 10 microM, expression of c-myc protein was significantly suppressed only by 20AS1 (4G) (62%), and was only weakly inhibited by 20SCR1 (4G) (32%). Furthermore, a small cell lung carcinoma cell line, Lu65, which can grow in suspension form, was highly resistant to 20AS1 (4G) treatment (IC50>20 microM). These results suggest that the cell growth inhibition by c-myc antisense oligonucleotides containing the contiguous four-guanosine (4G) sequence was possibly correlated with inhibition of cell adhesion, but not with inhibition of c-myc protein expression, via a sequence-specific non-antisense mechanism.

Base Sequence↗
PubMed1997

Decrease in class pi glutathione transferase mRNA levels by ultraviolet irradiation of cultured rat keratinocytes.

The effect of ultraviolet (UV) B irradiation on pi class glutathione transferase (GST-P) gene expression was examined in cultured rat keratinocytes. Immunoblotting demonstrated GST-P to be the major GST form in the cells, and it was significantly decreased following irradiation. Northern blot analysis revealed that the mRNA decreased to 10-25% of the initial value 24 h after irradiation at a dose of 40 mJ/cm2. No remarkable changes were observed at earlier time points. Hydrogen peroxide treatment enhanced GST-P mRNA expression, with a 70% increase at 250 microM concentration. Alterations in possible trans-acting factors were examined to clarify the mechanism of repression by UV irradiation. c-Jun mRNA was induced 3.5-fold at 4 h after irradiation, but by 24 h fell to a lower level than that observed initially. c-Fos mRNA was increased 10-fold at 1 h but was completely suppressed at 12 and 24 h. Thus, the changes of c-Jun and c-Fos mRNA differed from that of GST-P mRNA. The level of mRNA for silencer factor-B was decreased to less than 10% at 12 h. UV irradiation of cells transfected with the chloramphenicol acetyltransferase (CAT) reporter gene containing enhancer (GPE I) or silencer regions of the GST-P gene did not suppress CAT activity. Although basal expression of the GST-P gene was mainly dependent on GPE I, altered expression of c-jun, c-fos and other genes coding for factors possibly trans-acting on GPE I did not appear to be responsible for the decreased GST-P mRNA levels.

Animals↗
PubMed1997

Correlated expression of glutathione S-transferase-pi and c-Jun or other oncogene products in human squamous cell carcinomas of the head and neck: relevance to relapse after radiation therapy.

The expression of glutathione S-transferase (GST)-pi and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, in human squamous cell carcinomas of the head and neck was investigated immunohistochemically before and after radiation therapy, to examine whether these oncogene products might be involved in GST-pi expression, and also to examine the relationship between their expression and therapeutic response. Clinical response to radiation was evaluated in terms of both tumor regression and relapse over two-year follow-up periods. The overall positive rates in 83 carcinoma specimens before therapy were 60.2% for GST-pi and 28.9-51.8% for the individual oncogene products, the positive rates for the oncogene products being higher in GST-pi-positive than in GST-pi-negative cancers. c-Jun was most highly correlated with GST-pi expression. Following radiation, the expression of GST-pi and the oncogene products was altered in about a half of 30 patients. Eleven of the 18 patients who exhibited prior positivity for GST-pi showed negative conversion, while 4 of the 12 patients with prior negativity demonstrated positive conversion. In most cases, changes in c-Jun staining coincided with those in GST-pi. Regarding clinical response to radiation therapy, the positive rates for GST-pi and c-Jun before radiation were higher in the residual cancer or relapse cases than in the group showing complete response without relapse. Examination of 26 patients with laryngeal cancer revealed that relapse occurred more frequently in cases exhibiting positive reactions for GST-pi, c-Jun, or c-H-Ras. These results suggest a direct link between c-Jun and GST-pi in head and neck cancers before and after radiation. Although GST-pi and the oncogene products can be influenced by radiation, GST-pi and c-H-Ras expression may be a risk factor for relapse of laryngeal cancer.

Adult↗
PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate.

In our studies to find natural compounds with chemopreventive efficacy in foods, using azoxymethane (AOM)-induced colonic aberrant crypt foci and colonic mucosal cell proliferation as biomarkers, a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), present in the edible plant Languas galanga from Thailand was found to be effective. This study was conducted to test the ability of ACA to inhibit AOM-induced colon tumorigenesis when it was fed to rats during the initiation or post-initiation phase. Male F344 rats were given three weekly s.c. injections of AOM (15 mg/kg body weight) to induce colonic neoplasms. They were fed diet containing 100 or 500 ppm ACA for 4 weeks, starting one week before the first dosing of AOM (the initiation feeding). The other groups were fed the ACA diet for 34 weeks, starting one week after the last AOM injection (the post-initiation feeding). At the termination of the study (week 38), AOM had induced 71% incidence of colonic adenocarcinoma (12/17 rats). The initiation feeding with ACA caused significant reduction in the incidence of colon carcinoma (54% inhibition by 100 ppm ACA feeding and 77% inhibition by 500 ppm ACA feeding, P = 0.03 and P = 0.001, respectively). The post-initiation feeding with ACA also suppressed the incidence of colonic carcinoma (45% inhibition by 100 ppm ACA feeding and 93% inhibition by 500 ppm ACA feeding, P = 0.06 and P = 0.00003, respectively). Such inhibition was dose-dependent and was associated with suppression of proliferation biomarkers, such as ornithine decarboxylase activity in the colonic mucosa, and blood and colonic mucosal polyamine contents. ACA also elevated the activities of phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. These results indicate that ACA could inhibit the development of AOM-induced colon tumorigenesis through its suppression of cell proliferation in the colonic mucosa and its induction of GST and QR. The results confirm our previous finding that ACA feeding effectively suppressed the development of colonic aberrant crypt foci. These findings suggest possible chemopreventive ability of ACA against colon tumorigenesis.

Animal Feed↗
PubMed1997

The efficacy and safety of one-week triple therapy with lansoprazole, clarithromycin, and metronidazole for the treatment of Helicobacter pylori infection in Japanese patients.

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of 1-week, low-dose triple therapy with lansoprazole, clarithromycin, and metronidazole (LCM) for the cure of H. pylori infection and to establish the adequate dosage of a new triple therapy for Japanese patients. MATERIALS AND METHODS: One hundred four H. pylori-positive Japanese patients were assigned alternatively to one of two groups: one to receive either 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily for 1 week (LCM1; n = 52); the other to receive 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 500 mg metronidazole twice daily for 1 week (LCM2; n = 52). H. pylori infection was assessed by smear, culture, and histological assessment (Giemsa stain) performed before and 4 weeks after cessation of the therapy. RESULTS: The overall cure rates of H. pylori infection were 92.3% (48 of 52; 95% confidence interval (CI), 85% to 100%) in LCM1 and 92.3% (48 of 52; 95% CI, 85% to 100%) in LCM2. The cure rates in the patients without prior treatment were 95.7% (44 of 46; 95% CI, 89%-100%) in LCM1 and 95.7% (45 of 47; 95% CI, 89%-100%) in LCM2. Minor side effects were observed in 7.7% of LCM1 and 9.6% of LCM2, respectively. CONCLUSION: The LCM1 regimen consisting of 30 mg lansoprazole once daily, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily (the regular doses in ordinary use in Japan) is a highly effective and safe regimen for Japanese patients. LCM1 as a new triple therapy is a promising regimen for the first-line treatment of H. pylori infection in Japanese patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

A mutation in plasma platelet-activating factor acetylhydrolase (Val279-->Phe) is a genetic risk factor for stroke.

BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) is a phospholipid with multiple actions that include thrombosis and inflammation. It is inactivated by a plasma enzyme, PAF acetylhydrolase. Deficiency of this enzyme in plasma is caused by a missense mutation in the gene (Val279-->Phe). We have studied a possible association of this mutation with the risk of stroke. SUBJECTS AND METHODS: We studied 120 consecutive patients with cerebral thrombosis. The control group consisted of 134 patients matched for age and sex with minor complaints but without stroke. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF acetylhydrolase activity was determined by the method of Stafforini et al. RESULTS: The prevalence of the mutant gene was 43.4% in stroke patients (39.2% heterozygotes and 4.2% homozygotes), which was significantly higher than the 25.4% in control subjects (22.4% heterozygotes and 3.0% homozygotes) (chi 2 = 9.22, P < .01). The prevalence was slightly higher in stroke patients without hypertension than those with hypertension, but the difference was not significant. The patients with family histories of stroke had a slightly higher but not a significant prevalence of the mutant gene as compared with those without family histories of stroke. Plasma PAF acetylhydrolase activity was higher in patients than in control subjects, in normal subjects, or patients with a heterozygous genotype. CONCLUSIONS: These results suggest that plasma PAF acetylhydrolase deficiency may be a risk factor for stroke. This may explain the relatively high prevalence of stroke in Japan, as the mutation is more common among Japanese than Caucasians.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Bacterial pneumonia causes augmented expression of the secretory leukoprotease inhibitor gene in the murine lung.

The cDNA of murine secretory leukoprotease inhibitor (SLPI) was cloned from a mouse lung cDNA library. The amino acid sequence deduced from the cDNA showed 58 and 51% homology with those of human and porcine SLPI, respectively. A two-domain structure with similar amino acid sequences, four intradomain disulfide bonds, and high proline content, which are characteristics common to human and porcine SLPI, was also found in the mouse protein. The amino acid residues for the signal sequence and active site are also conserved in mouse SLPI. RNase protection assay showed the expression of the SLPI gene in liver, intestine, spleen, and epididymis, suggesting the distribution of SLPI in tissues other than lung and seminal vesicles. In the lung infected with Streptococcus pneumoniae strain FP1284, 10 h after inoculation of bacteria the number of SLPI mRNA transcripts was three times higher than baseline. The increased level of expression remained constant for at least 48 h. This result clearly contrasts to that obtained for spleen, in which the SLPI mRNA transcript level was mostly unchanged during the course of pneumonia. These facts suggested the local regulation of the SLPI gene expression in vivo in response to inflammatory stimuli at the site of inflammation.

Amino Acid Sequence↗
PubMed1997

Simultaneous or delayed administration of hepatocyte growth factor equally represses the fibrotic changes in murine lung injury induced by bleomycin. A morphologic study.

Hepatocyte growth factor (HGF) is a humoral mediator of epithelial-mesenchymal interactions, acting on a variety of epithelial cells as mitogen, motogen, and morphogen. Exogenous HGF acts as a hepatotrophic factor and a renotrophic factor during experimental injury. To investigate whether HGF has a pulmotrophic function, human recombinant HGF was administered to C57BL/6 mice with severe lung injury by bleomycin (BLM). Low dose simultaneous and continuous administration of HGF (50 micrograms/mouse/7 d) with BLM (100 mg/mouse/7 d) repressed fibrotic morphological changes at 2 and 4 wk. Ashcroft score showed a significant difference in lung fibrosis with and without HGF at 4 wk (3.7 +/- 0.4 versus 4.9 +/- 0.3, p < 0.05). Furthermore, either simultaneous or delayed administration of high dose HGF (280 micrograms/mouse/14 d) equally repressed fibrotic changes by BLM when examined at 4 wk (Ashcroft score: 2.6 +/- 0.4 and 2.4 +/- 0.2 versus 4.1 +/- 0.2, p < 0.01). Hydroxyproline content in the lungs was significantly lower in mice with either simultaneous or delayed administration of high dose HGF as compared to those administered BLM alone (121.8 +/- 8.1% and 113.2 +/- 6.2% versus 162.7 +/- 4.6%, p < 0.001). These findings indicate that exogenous HGF acts as a pulmotrophic factor in vivo and prevents the progression of BLM-induced lung injury when administered in either a simultaneous or delayed fashion. HGF may be a potent candidate to prevent or treat lung fibrosis.

Animals↗
PubMed1997

Hepatocyte growth factor in bronchoalveolar lavage fluids and cells in patients with inflammatory chest diseases of the lower respiratory tract: detection by RIA and in situ hybridization.

Pulmonary fibrosis is a chronic inflammatory disorder characterized by diffuse fibrous remodeling of alveolar spaces. Although much interest is focused on mechanisms of the inflammatory process in pulmonary fibrosis, little is known about the repair and regenerative process. Hepatocyte growth factor (HGF), originally discovered as a mitogen for hepatocyte regeneration, is now recognized as a multifunctional mesenchymal factor for epithelial regeneration, including the regeneration of alveolar type II epithelial cells. Involvement of HGF and its receptor (c-met) is evident in animal models of acute lung injury produced by hydrochloride inhalation. We studied the role of HGF in patients with idiopathic pulmonary fibrosis (IPF) (25 cases), lung fibrosis associated with rheumatoid arthritis (22 cases), and sarcoidosis (39 cases). Immunohistochemical evaluation demonstrated that hyperplastic alveolar type II epithelial cells, as well as alveolar macrophages, were strongly stained with anti-HGF antibody in tissues of patients with IPF. The concentration of HGF in bronchoalveolar lavage fluid (BALF) was significantly higher than in normal controls (0.23 +/- 0.09 pg/microg) in patients with IPF (0.77 +/- 0.88 pg of HGF/microg of albumin, P < 0.001), lung fibrosis associated with rheumatoid arthritis (0.50 +/- 0.64 pg/microg, P < 0.01), and sarcoidosis (0.41 +/- 0.61 pg/microg, P < 0.05). In situ hybridization revealed mRNA for HGF in alveolar macrophages (especially small monocytelike macrophages). These results indicate that the increase in HGF concentration in patients' peripheral air spaces is due to augmented HGF production by alveolar epithelial cells and alveolar macrophages. HGF, through a paracrine mechanism, may play an important role in the repair and healing of the inflammatory lung damage in pulmonary fibrosis.

Adult↗
PubMed1997

Cis-acting region associated with lung cell-specific expression of the secretory leukoprotease inhibitor gene.

Secretory leukoprotease inhibitor (SLPI) is a serine protease inhibitor, produced locally in respiratory and genital glands, but not in the liver. In the present study the promoter region of this gene was analyzed to better understand the molecular mechanisms involved in transcriptional regulation. DNase-I hypersensitive sites were detected within 1 kbp upstream of exon I in chromatin structures of type II pneumocyte cell line A549 and utero-cervical cell line HeLa, both of which express SLPI mRNA transcripts. The function of the SLPI promoter encompassing these DNase-I hypersensitive sites has been studied by deletion analysis with the luciferase gene as a transient expression vector. In this analysis, we found three transcription control regions that function in A549 cells but not in nonlung cell lines, such as HeLa and hepatoma Hep G2. Among three cis-regulatory regions, a proximal 41-bp region (-132 to -92 bp relative to the transcription start site) is responsible for the most striking magnitude of transcriptional activity. This region corresponds to the transcriptional activating sequence detected in another lung cell line, HS-24, indicating that this 41-bp sequence is required for lung cell-specific expression. An electrophoretic mobility shift assay demonstrated that this 41-bp promoter region contains an 11-bp recognition sequence for two nuclear binding proteins, one of which is abundant in lung cell lines, and the other in nonlung cell lines. These results suggest that the ratio of these two nuclear binding proteins confers the cell type specificity on the expression pattern of the SLPI gene.

Adenocarcinoma↗
PubMed1997

Inhibitory effects of glibenclamide and pertussis toxin on the attenuation of ischemia-induced myocardial acidosis following ischemic preconditioning in dogs.

Ischemic preconditioning is known to be mediated by several humoral factors, such as adenosine, norepinephrine, and bradykinin. We examined intracellular signal transduction of ischemic preconditioning following receptor stimulation. Alterations in the pH of the ischemic bed were monitored to assess the response of control and ischemic-preconditioned myocardium to glibenclamide and pertussis toxin. Pentobarbital-anesthetized open-chest dogs were subjected to 40 min of ligation of the left anterior descending coronary artery. Ischemic preconditioning was elicited by 25-min periods of coronary ligation followed by 5 min of reperfusion before a 40-min period of ligation. Glibenclamide (0.3 mg/kg)was given i.v. 20 min before the onset of ischemic preconditioning. Pertussis toxin (6-10 micrograms/kg) was given i.v. 3 days before the experiment. Tissue myocardial pH was measured by a glass micro-pH electrode. Ischemia for 5 min decreased myocardial pH and reperfusion returned it to the preischemic levels. Ischemia for 40 min decreased the myocardial pH from 7.43 +/- 0.06 to 6.43 +/- 0.08. Ischemic preconditioning significantly attenuated the decrease in myocardial pH (6.57 +/- 0.06) induced by 40 min of ischemia. Pretreatment with either glibenclamide or pertussis toxin completely abolished the effect of ischemic preconditioning on ischemic myocardial acidosis. Ischemic preconditioning can attenuate ischemia-induced myocardial acidosis in dogs, and this effect is mediated by activation of adenosine triphosphate-sensitive potassium channels and pertussis toxin-sensitive guanosine triphosphate-binding protein.

Acetylcholine↗