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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 379 records · Page 21Linked to original sources
PubMed1997

Serum sialyl lewis X-i antigen levels in non-small cell lung cancer: correlation with distant metastasis and survival.

To evaluate the correlation between serum levels of sialyl Lewis X-i antigen and distant metastasis and survival in patients with non-small cell lung cancer (NSCLC), we measured the serum levels of the tumor marker in 371 patients with untreated NSCLC. The sialyl Lewis X-i antigen level was measured using a RIA kit. In patients with adenocarcinoma or other NSCLC subtypes, there was a correlation between serum sialyl Lewis X-i antigen and stage of the disease (P = 0.0001 and P = 0.0015, respectively). Levels of the marker varied significantly depending on the number of metastatic organs in adenocarcinoma (P = 0.0089) and in other NSCLC subtypes (P = 0.002). Univariate analysis showed that survival of NSCLC patients with high (more than 100 units/ml) sialyl Lewis X-i antigen levels was significantly poorer than that of patients with low antigen levels (P = 0.0001). Multivariate analysis using Cox's proportional hazard model showed that high sialyl Lewis X-i antigen levels correlated significantly with poor survival (P = 0.004). Our data suggest that a high serum level of sialyl Lewis X-i antigen seems to be an indicator of the presence of metastasis and might indicate the need for a careful investigation of all putative metastatic sites. The serum levels of sialyl Lewis X-i antigen may reflect the extension of metastasis and would be helpful in considering treatment options.

Adult↗
PubMed1996

Cloning and characterization of a cDNA for rat CD30 homolog and chromosomal assignment of the genomic gene.

CD30 is a member of the tumor necrosis factor receptor superfamily, which is expressed on some activated lymphocytes, virus-infected cells and transformed lymphocytes. To facilitate our understanding of biological functions and functional domains, we isolated rat cDNA clones encoding the rat homolog of human CD30 from a cDNA library of a rat T-cell line, TARL-2. The nucleotide sequence of the cDNA showed 73% homology with that of human CD30. The deduced rat CD30 protein consisted of 493 amino acids with an M(r) of 59 160 and contained a single transmembrane domain. It lacked the second repeat of the cysteine-rich motif in the extracellular domain found in human CD30. The amino acid sequence showed 51.8 and 61.2% identity with the cysteine-rich and the cytoplasmic domains, respectively. In the cytoplasmic domain, however, the amino acid sequence was highly conserved in about 100 residues near the C-terminus showing 77.7% identity, whereas the rest of the cytoplasmic domain showed 45.2% identity. This conservation suggests the functional importance of this region. Comparison with the recently reported mouse CD30 revealed 83.7% conservation of the amino acid sequence and a common structure of the extracellular domain which lacks the second cysteine-rich motif. Northern blots revealed a 3.4-kb mRNA in the PHA-activated spleen cells and human T-cell leukemia virus type 1 (HTLV-1)-infected rat T-cell lines, whereas smaller transcripts of 2.3 kb were found in the lung. A rabbit polyclonal antibody raised against GST-fusion protein of the cytoplasmic domain detected bands with an apparent M(r) of 80 kDa and 100- 110 kDa expressed in TARL-2 and spleen cells. Transient overexpression of rat CD30 in TARL-2 cells activated HIV LTR in a NF-kappa B site-dependent manner, indicating that CD30 signals activate NF-kappa B. The chromosomal location of the gene was identified by fluorescence in situ hybridisation at 5q36.2, and appeared to correspond to human 1p36, where human CD30 has been mapped. The identification and characterization of the rat counterpart of human CD30 will facilitate studies of the biological function of this molecule.

Amino Acid Sequence↗
PubMed1996

Protein kinase C plays a key role in the cross-talk between intracellular signalings via prostanoid receptors in a megakaryoblastic cell line, MEG-01s.

In a previous study, we characterized prostanoid and thrombin receptors expressed on a megakaryoblastic cell line, MEG-01s (Blood 78, 2328-2336, 1991). In this study, we examines the mechanism of cross-talk between intracellular Ca2+ ([Ca2+]i) and cAMP signalings through prostanoid and thrombin receptors. Addition of a thromboxane (TX)A2 mimetic (U46619 or STA2) or thrombin stimulated the formation of inositol phosphates and dose-dependently augmented a prostaglandin (PG)I2 mimetic (iloprost)- or forskolin-induced cAMP formation. 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin, to lesser extent, also augmented iloprost-induced cAMP formation. The enhancing effect of U46619 or TPA on cAMP formation was inhibited by prolonged pretreatment of the cells with TPA (2.5 microM, 24 h), but not with calmodulin-antagonists; W-7, W-5, or KN-62. The elevation of [Ca2+]i induced by thrombin, STA2 or PGE2 was significantly suppressed by pretreatment of the cells with TPA (100 nM) as well as cAMP mimetics such as dibutyryl cAMP (5 mM), forskolin (5 microM) and iloprost (1 microM). These results suggest the key role of PKC on the cross-talk between [Ca2+]i and cAMP signalings through prostanoid and thrombin receptors; PKC, which is activated with TXA2 or thrombin, concomitantly suppress further [Ca2+]i elevation and enhances the PGI2 receptor-mediated cAMP formation, which, in turn, suppress [Ca2+]i elevation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1996

Cloning, sequencing, and high level expression of the genes encoding adenosylcobalamin-dependent glycerol dehydrase of Klebsiella pneumoniae.

The gld genes encoding adenosylcobalamin-dependent glycerol dehydrase of Klebsiella pneumoniae were cloned by cross-hybridization with a DNA fragment of Klebsiella oxytoca diol dehydrase genes. Since the Escherichia coli clones isolated did not show appreciable enzyme activity, plasmids for high level expression of cloned genes were constructed. The enzyme expressed in E. coli was indistinguishable from the wild-type glycerol dehydrase of K. pneumoniae by the criteria of polyacrylamide gel electrophoretic, immunochemical, and catalytic properties. It was also shown that the recombinant functional enzyme consists of Mr 61,000, 22,000, and 16, 000 subunits. Sequence analysis of the genes revealed four open reading frames separated by 2-12 bases. The sequential three open reading frames from the first to the third (gldA, gldB, and gldC genes) encoded polypeptides of 555, 194, and 141 amino acid residues with predicted molecular weights of 60,659(alpha), 21,355(beta), and 16,104(gamma), respectively. High level expression of these three genes in E. coli produced more than 14-fold higher level of fully active apoenzyme than that in K. pneumoniae. It was thus concluded that these are the genes encoding the subunits of glycerol dehydrase. The deduced amino acid sequences of the three subunits were 71, 58, and 54% identical with those of the alpha, beta, and gamma subunits of diol dehydrase, respectively, but failed to show any apparent homology with other proteins.

Amino Acid Sequence↗
PubMed1996

Circadian blood pressure variation related to morbidity and mortality from cerebrovascular and cardiovascular diseases.

The mortality rate of stroke has decreased dramatically over the past 30 years in Japan, but the prevalence of cerebral infarction has increased, mainly because of the higher incidence of nonfatal cerebral infarction in the elderly. Significant advances in the development of antihypertensive drugs over the last 30 years have contributed to the decrease in stroke mortality, but antihypertensive treatment appears to relate to an increase in the prevalence of cerebral infarction in the elderly. We investigated the risks of low BP levels determined by ambulatory BP monitoring and home BP measurements to clarify the previously reported J-shaped relationships between the incidence of ischemic cardiovascular disease and BP levels after treatment. A long-term prospective study of all causes of mortality and cerebrovascular and cardiovascular mortality has been conducted in Ohasama, Japan, since 1987. Cox proportional hazard model after adjusting for age and sex demonstrated that during a 5-year follow-up period involving 893 of the subjects aged 50 years and over in this cohort, those with the lowest quintile of ambulatory BP levels exhibited a significantly high hazard ratio of cardiovascular as well as all causes of mortality. During the same follow-up period in 1,226 subjects aged 50 years and over, those with the lowest and highest quintiles of home BP levels demonstrated a significantly high hazard ratio of cardiovascular as well as all causes of mortality (i.e., J-shaped relationship). The amplitude of the fall in nocturnal BP obtained by ambulatory BP monitoring correlated positively with the severity of silent cerebrovascular lesions in elderly women, but not in elderly men. These results suggest the significantly high risk associated with low BP levels, which can be determined only by ambulatory and home BP measurements, but not by casual BP measurements.

Age Factors↗
PubMed1996

cDNA cloning and chromosomal mapping of a novel human GAP (GAP1M), a GTPase-activating protein of Ras.

We have previously isolated a novel Ras GTPase-activating protein (Ras GAP), Gap1m, from rat brain. Gap1m is considered to be a negative regulator of the Ras signaling pathways, like other Ras GAPs, neurofibromin, which is a gene product of the neurofibromatosis type I gene, and p120GAP. In this study we have isolated a human cDNA of this Gap and mapped the gene. The gene encodes a protein of 853 amino acids that shows 89% sequence identity to rat Gap1m. The human gene was mapped to chromosome 3 by PCR analysis on a panel of human-mouse hybrid cells. FISH analysis refined the location of the gene further to 3q22-q23.

Amino Acid Sequence↗
PubMed1996

Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).

We have molecularly cloned a cDNA encoding a protein uniquely expressed and hyperphosphorylated at tyrosine residues in a Ki-1 lymphoma cell that contained chromosomal translocation t(2;5). The encoded protein p80 was shown to be generated by fusion of a protein-tyrosine kinase and a nucleolar protein B23/nucleophosmin (NPM). The coding sequence of this cDNA turned out to be virtually identical to that of the fusion cDNA for NPM-anaplastic lymphoma kinase (ALK) previously cloned from the transcript of the gene at the breakpoint of the same translocation. Overexpression of p80 in NIH 3T3 cells induced neoplastic transformation, suggesting that the p80 kinase is aberrantly activated. The normal form of p80 was predicted to be a receptor-type tyrosine kinase on the basis of its sequence similarity to the insulin receptor family of kinases. However, an immunofluorescence study using COS cells revealed that p80 was localized to the cytoplasm. Thus, subcellular translocation and activation of the tyrosine kinase presumably by its structural alteration would cause the malignant transformation. We also showed that a mutant p80 lacking the NPM portion was unable to transform NIH 3T3 cells. Thus, the NPM sequence is essential for the transforming activity, suggesting that the chromosomal translocation is responsible for the oncogenesis. Finally, Shc and insulin receptor substrate 1 (IRS-1) were tyrosine-phosphorylated and bound to p80 in p80-transformed cells. However, mutants of p80 that were defective for binding to and phosphorylation of Shc and insulin receptor substrate 1 could transform NIH 3T3 cells. Association of these mutants with GRB2 was still observed, suggesting that interaction of p80 with GRB2 but not with Shc or IRS-1 was relevant for cell transformation.

3T3 Cells↗
PubMed1996

A point mutation within each of two ATP-binding motifs inactivates the functions of elongation factor 3.

We have investigated how point mutations in the two ATP-binding motifs (G(463)PNGCGK(469)ST and G(701)PNGAGK(707)ST) of elongation factor 3 (EF-3) affect ribosome-activated ATPase activity of EF-3, polyphenylalanine synthesis, and growth of Saccharomyces cerevisiae. The point mutation impaired the ribosome-activated ATPase activity of EF-3, when glycine(463 and 701) and lysine(469 and 707) were replaced with valine and arginine, respectively. Thus, each glycine and lysine residue in both ATP-binding motifs is indispensable for EF-3's binding with ATP and the ensuing generation of ribosome-activated ATPase activity. Additionally, the mutant EF-3s did not catalyze polyphenylalanine synthesis in vitro when each glycine(463 and 701) was replaced with valine. The mutant EF-3s did not support cell growth in TEF3-disrupted S. cerevisiae, when each lysine(469 and 707) and glycine(463) was replaced with arginine and valine, respectively. Thus, each of the two ATP-binding motifs of EF-3 is indispensable for the ribosome-activated ATPase activity of EF-3, which is required for protein synthesis and cell growth in S. cerevisiae.

Adenosine Triphosphatases↗
PubMed1996

Localization of 7H6 tight junction-associated antigen along the cell border of vascular endothelial cells correlates with paracellular barrier function against ions, large molecules, and cancer cells.

To study the regulation of the endothelial barrier, we examined the relationship between the paracellular barrier function and the expression of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression of 7H6 antigen as parameters. RLE cells cultured at a confluent cell density did not express immunohistochemically demonstrable 7H6 antigen and had low paracellular barrier functions. However, treatment of the endothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-retinoic acid for 4 days induced 7H6 antigen preferentially at the cell border and simultaneously enhanced the barrier function twofold, in terms of TER and fluxes of albumin and dextran. Furthermore, RA-treated RLE cell monolayers with the enhanced barrier function significantly inhibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial role in the regulation of paracellular barrier function not only in epithelial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo function as a barrier between blood and tissues against metastatic cancer cells.

Animals↗
PubMed1996

Positive and negative regulation of cell proliferation through prostaglandin receptors in NIH-3T3 cells.

Among major eicosanoids and their analogs, prostaglandin (PG) F2 alpha > PGD2 > PGE1 > or = PGE2 > iloprost, a stable agonist of PGI2, dose-dependently stimulated DNA synthesis in quiescent NIH-3T3 cells. PGF2 alpha, PGD2, and PGE2, in that order, formed inositol phosphates and elevated intracellular Ca2+ ([Ca2+]i) but did not form cAMP nor inhibit forskolin-induced cAMP formation. Iloprost, PGI2, and PGE1 induced cAMP formation dose dependently with an ED50 of around 10(-7) M, and PGE2 at more than 10(-6) M did it. [3H]PGF2 alpha and [3H]PGD2 bindings membranes from NIH-3T3 cells were displaced in the order of PGF2 alpha > PGD2 > or = PGE2, while [3H]PGE2 binding was displaced by PGE2 > PGD2 > or = PGF2 alpha. Expression of mRNA encoding EP1 and EP4 (EP2) subtypes could be detected by reverse transcription- polymerase chain reaction using primers specific for EP1 and EP4 (EP2) cDNAs, but not that of EP3 subtype mRNA. The dose dependence of cAMP formation on iloprost and PGI2 and that of [Ca2+]i elevation on PGF2 alpha, D2, and E2 were similar to that of [3H]thymidine incorporation on the corresponding agonists. Fluprostenol (1 microM), a PGF2 alpha receptor agonist > 17-phenyl-trinor-PGE2 (1 microM), an EP1 receptor agonist stimulated [3H]thymidine incorporation, but an EP3 receptor agonist, ONO-AP-324 nor an EP4 (EP2) receptor agonist, 11-deoxy-PGE1 (1 microM) did not. Iloprost, dibutyryl cAMP, forskolin, or cholera toxin, when applied alone, enhanced [3H]thymidine incorporation, while they inhibited [3H]thymidine incorporation induced by submaximal concentrations of PGF2 alpha or epidermal growth factor (EGF), when applied within 12 hr after agonist stimulation. These results suggest that the proliferation of NIH-3T3 cells is stimulated by PGs via the PGF2 alpha receptor, EP1 subtype of PGE receptor, and the PGI2/PGE1 receptor through [Ca2+]i- and cAMP-dependent pathways, and that cAMP pathway negatively cross-talks with [Ca2+]i-or receptor tyrosine kinase-mediated DNA synthesis in a cell cycle-dependent manner.

3T3 Cells↗
PubMed1996

Telomere shortening in peripheral blood cells was related with aging but not with white blood cell count.

Telomeres in somatic cells are progressively shortened with aging. We investigated the relationship between the telomere length and other factors which may affect the frequency of cell divisions, in peripheral blood cells. Shortening of telomeric repeats was correlated with aging (p < 0.0001), but not with white blood cell count, neutrophil count, and smoking habit. Not only the number of cell divisions, but also some other factors, such as upregulation level of telomerase activity concomitant with the cell division in hematopoietic progenitor cells, might affect the length of telomeric repeats in blood cells.

Adult↗
PubMed1996

Capsaicin-sensitive sensory neurons are involved in bicarbonate secretion induced by lansoprazole, a proton pump inhibitor, in rats.

Lansoprazole, a proton pump inhibitor, exerts prominent antiulcer activity via both antisecretory and mucosal protective actions. Although the antisecretory action has been explained by inactivation of (H+, K+)-ATPase in parietal cells, the mode of mucosal protective action remains to be elucidated. In the present study, the effect of lansoprazole on duodenal bicarbonate secretion was studied in anesthetized rats to clarify the mode of the mucosal protective action. Lansoprazole (0.1 mM) applied topically to the duodenum significantly (P < 0.01) increased bicarbonate secretion by 0.36 +/- 0.11 microeq/15 min (21 +/- 5%) compared with the value in the vehicle control. Topical administration of capsaicin (10 mg/ml) in the duodenum and intravenous infusion of vasoactive intestinal peptide (10 micrograms/kg/hr) increased bicarbonate secretion. Five-minute perfusion of the duodenal loop with 100 mM HCl increased bicarbonate secretion. Administration of lansoprazole (0.3 and 1 mg/kg, intravenously) 60 min before luminal acidification enhanced the acid-induced bicarbonate secretion dose-dependently and significantly (P < 0.01). In the capsaicin-pretreated rats, the effects of lansoprazole on basal and acid-induced bicarbonate secretion were significantly (P < 0.05) decreased compared with that of control group. These results indicate that lansoprazole increases basal and acid-induced bicarbonate secretion in the duodenum in rats and that capsaicin-sensitive sensory neurons may be involved in the mode of action for these effects.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Deconjugation of bilirubin accelerates coprecipitation of cholesterol, fatty acids, and mucin in human bile--in vitro study.

To examine the initial step of brown pigment gallstone formation, sterile human gallbladder bile samples were incubated with or without beta-glucuronidase in vitro. Enhanced bilirubin deconjugation achieved by adding beta-glucuronidase significantly accelerated the formation of a precipitate that contained bilirubin (28.2 +/- 3.8% of dry weight), cholesterol (14.3 +/- 5.2%), free fatty acids (12.0 +/- 1.3%), and glycoprotein (10.0 +/- 6.7%). Both the composition and scanning electron microscopic appearance of the precipitate were similar to these features in brown pigment gallstones. The cholesterol saturation index and nucleation time in the supernatant did not change with various incubation periods. The weight ratios of bilirubin to cholesterol in the precipitates correlated with those in bile (r = 0.76; P = 0.017). Gel chromatography of the precipitate showed high molecular weight glycoprotein to be the major constituent. Bilirubin, cholesterol, fatty acids, and mucin were found to coprecipitate in accordance with bilirubin deconjugation, which process may play an important role in an early stage of the formation of brown pigment gallstones.

Bile↗
PubMed1996

Determination of selenium in the human brain by graphite furnace atomic absorption spectrometry.

For the investigation of neurological disorders, a development of simple and accessible methods for determining selenium in human brain samples is required. We devised a method of determining selenium using graphite furnace atomic absorption spectrometry (GFAAS). An electrodeless discharge lamp provided the sufficient sensitivity to determine brain selenium. The matrix interferences were avoided by using high temperature, a prolonged pyrolysis step, and a palladium matrix modifier. The technique of standard addition was used to evaluate the sample concentrations. The accuracy of the method was confirmed by a bovine liver reference material. The detection limit of selenium was 0.04 ng. The determined selenium concentrations of human brain cortex and white matter were higher than those of putamen (115-155 and 206-222 ng/g wet wt, respectively). These GFAAS values agreed with those obtained by fluorometric analysis (r = 0.91, n = 10). Moreover, the GFAAS values were compatible to those reported by other researchers (99-274 ng/g wet wt), in which selenium concentrations in putamen also tended to be higher than the other two regions. We conclude that GFAAS is useful for selenium analysis in brain samples.

Brain↗
PubMed1996

Internal thoracic artery holder for coronary artery bypass grafting.

An arterial graft holder was designed to facilitate coronary artery bypass grafting using arterial conduits. It is possible to open the heel of the arterial conduit and stitch the most difficult angle of the anastomosis under optimal visualization. This internal thoracic artery holder is atraumatic and protects the arterial conduit wall from crush injuries caused by vascular forceps. Anastomosis without the endothelial injury may provide long-term patency of the coronary artery bypass graft.

Anastomosis, Surgical↗
PubMed1996

Intraoperative implantation of percutaneous left ventricular assist system.

The percutaneous left ventricular assist system, using modified Dennis technique, has been used successfully to treat patients experiencing severe cardiogenic shock in a variety of nonsurgical situations. Fluoroscopy is generally essential for implantation. Our experience with the implantation of the percutaneous left ventricular assist system during operations is described here. The percutaneous left ventricular assist system was applied using transesophageal echocardiographic imaging and by leading with the index finger through the right atrium without fluoroscopy.

Aged↗