Biomedical subjects

Y Okamoto

Publications and source records attributed to Y Okamoto.

At least 19 recordsLinked to original sources

PubMed1999

Comparison between chemoradiation protocol intended for organ preservation and conventional surgery for clinical T1-T2 esophageal carcinoma.

PURPOSE: This retrospective study was designed to compare treatment results of the chemoradiation protocol with conventional surgery for thoracic T1-T2 esophageal squamous cell carcinoma. METHODS AND MATERIALS: Sixty-six patients with esophageal carcinoma, clinically diagnosed as T1 (tumor invading lamina propria or submucosa) or T2 (tumor invading muscularis propria) were treated for 12 consecutive years, from July 1986 to January 1998. The conventional surgery group included 30 patients who underwent esophagectomy with regional lymph node dissection. Twenty-one of them received postoperative radiotherapy. Thirty-six patients were assigned to the chemoradiation protocol, consisting of neoadjuvant chemoradiotherapy (44 Gy; CDDP: 60 mg/m2, day 1, bolus; 5-FU: 400 mg/m2, day 1-4, continuous), followed by either definitive radiotherapy with high-dose-rate intraluminal brachytherapy (total 70 Gy) for responders or surgery for nonresponders as in the conventional surgery group. Surgical candidates in both groups received intraoperative radiotherapy for abdominal lymphatics since 1991. RESULTS: In the protocol group, 4 patients underwent radical surgery after neoadjuvant chemoradiotherapy, and the remaining 32 underwent definitive chemoradiotherapy. Local control rates at 1 and 3 years were 85% and 70% in the T1/protocol group versus 91% and 80% in the T1/surgery group, and 83% and 83% in the T2/protocol group versus 94% and 80% in the T2/surgery group, respectively. There was no statistical significance. Overall 1- and 3-year survival rates were 100% and 83% in the T1/protocol group versus 82% and 72% in the T1/surgery group (p = 0.36), and 100% and 51% in the T2/protocol group, versus 95% and 68% in the T2/surgery group p = 0.61), respectively. There was no treatment-related mortality in either group. The rates of esophageal conservation were 92% in the T1/protocol group and 58% in the T2/protocol group. CONCLUSION: The chemoradiation protocol can result in comparable survival with conventional surgery for patients with T1-T2 esophageal carcinoma. A randomized trial between definitive chemoradiotherapy and surgery is required.

Aged↗

PubMed1999

Efficacy of the mobilization of peripheral blood stem cells by granulocyte colony-stimulating factor in pediatric donors.

The advantages/disadvantages of the use of peripheral blood stem cells (PBSCs) for allogeneic transplantation still need to be clarified, particularly in children. We compared the kinetics, efficacy, and safety of PBSC mobilization by granulocyte colony-stimulating factor (G-CSF) and collection by apheresis between healthy pediatric and adult donors. A total of 19 pediatric (median age, 6 years) and 25 adult healthy donors (median age, 37 years) were given 10 micro/kg/day of G-CSF for 5 consecutive days for PBSC mobilization, which were harvested by apheresis on days 5 and/or 6. All of the donors tolerated the whole procedures. Serum trough levels of G-CSF determined by ELISA were significantly lower in the 16 pediatric donors evaluated than in adults (n = 16) on days 3 and 4 (P < 0.05). Although the WBC counts on days 4 and 5 were significantly higher in adults than in children (P = 0.006 and 0.004, respectively), the numbers of circulating CD34+ cells/unit of blood were identical. The number of blood CD34+ cells collected per unit of blood processed was identical in both donor populations. We propose that PBSCs could be effectively mobilized and collected in small children so that they could be donors for adult patients.

Adolescent↗

PubMed1999

Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions.

The scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 (CD36 and LIMPII Analogous-1) have recently been identified to bind HDL and mediate the selective uptake of HDL lipids. Tissue distribution of both murine and human receptors is quite similar, in that they are expressed abundantly in liver and steroidogenic tissues. However, expression and function of the human SR-BI (hSR-BI), in the periphery of reverse cholesterol transport such as macrophages, are still unclear. In the present study, we have raised two different kinds of anti-hSR-BI polypeptide antibodies (Abs): one against the extracellular domain and the other against the intracellular domain. We have investigated the expression of hSR-BI mRNA and immunoreactive mass in freshly isolated cultured human monocyte-derived macrophages (hMphi) and in atherosclerotic lesions. Contrary to the earlier report, hSR-BI mRNA was expressed in cultured hMphi and markedly upregulated with differentiation, determined by Northern blot and reverse transcriptase-based polymerase chain reaction analyses. The mRNA expression pattern during differentiation of hMphi was very similar to those of SR class A and another member of SR class B, CD36. Protein expression was confirmed by Western blot analyses with the above Abs to show a major 83-kDa band. Modified lipoproteins such as oxidized LDL and acetylated LDL induced a 5-fold increase in mRNA and protein expression of hSR-BI. Confocal immunofluorescence microscopy demonstrated that hSR-BI immunoreactive mass was detectable as a heterogeneous, punctate staining pattern. Furthermore, immunohistochemical analysis showed that immunoreactive mass of hSR-BI was detected in foam cells in human aortic atherosclerotic lesions and that there was no significant difference of staining patterns between the two Abs. This study clearly demonstrates that hSR-BI is expressed in the lipid-laden macrophages in human atherosclerotic lesions, suggesting that it is very important to know its function and regulation in hMphi to understand the biological utility of this molecule.

Animals↗

PubMed1999

Subcellular mechanisms of endothelin action in vascular system.

To elucidate the role of endothelin in the regulation of vascular function, the cellular and subcellular mechanisms for the synthesis of endothelin and the function of endothelin-receptors have been studied extensively. In this article, recent results regarding these problems are reviewed. (1) Oxidatively modified low-density-lipoprotein (LDL) reduces nitric oxide (NO) release via inhibition of the high-affinity arginine transporter of endothelial cells. (2) Endothelin-1-induced vasoconstriction is mediated by Ca2+ influx through a non-selective cation channel sensitive to 1-[beta-[3-(4-methoxyphenyl) propoxyl]-4-methoxyphenethyl]-1H-imidazole HCl (SK & F96365). (3) A distinct domain of the endothelin-receptor is required for the coupling of different G(alpha)-proteins. (4) Endothelin ET(A) receptor-mediated mitogenic activity is mediated by two pathways, one classical protein kinase C(PKC)-dependent, and the other phosphoinositide 3-kinase dependent. Both stimulate mitogen-activated protein kinase (MAPK). Endothelin ET(B) receptor-mediated mitogenic activity is also mediated by the PKC-dependent pathway. In contrast, endothelin ET(B) receptor-mediates differentiation and apoptosis via G(alpha)i coupling.

Animals↗

PubMed1999

The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs).

Serine/arginine-rich (SR) proteins play an important role in constitutive and alternative pre-mRNA splicing. The C-terminal arginine-serine domain of these proteins, such as SF2/ASF, mediates protein-protein interactions and is phosphorylated in vivo. Using glutathione S-transferase (GST)-SF2/ASF-affinity chromatography, the SF2/ASF kinase activity was co-purified from HeLa cells with a 95-kDa protein, which was recognized by an anti-SR protein kinase (SRPK) 1 monoclonal antibody. Recombinant SRPK1 and SRPK2 bound to and phosphorylated GST-SF2/ASF in vitro. Phosphopeptide mapping showed that identical sites were phosphorylated in the pull-down kinase reaction with HeLa extracts and by recombinant SRPKs. Epitope-tagged SF2/ASF transiently expressed in COS7 cells co-immunoprecipitated with SRPKs. Deletion analysis mapped the phosphorylation sites to a region containing an (Arg-Ser)8 repeat beginning at residue 204, and far-Western analysis showed that the region is required for binding of SRPKs to SF2/ASF. Further binding studies showed that SRPKs bound unphosphorylated SF2/ASF but did not bind phosphorylated SF2/ASF. Expression of an SRPK2 kinase-inactive mutant caused accumulation of SF2/ASF in the cytoplasm. These results suggest that the formation of complexes between SF2/ASF and SRPKs, which is influenced by the phosphorylation state of SF2/ASF, may have regulatory roles in the assembly and localization of this splicing factor.

Glutathione Transferase↗

PubMed1999

The folding funnel landscape for the peptide Met-enkephalin.

We study the free energy landscape of the small peptide Met-enkephalin. Our data were obtained from a generalized-ensemble Monte Carlo simulation taking the interactions among all atoms into account. We show that the free energy landscape resembles that of a funnel, indicating that this peptide is a good folder. Our work demonstrates that the energy landscape picture and folding concept, developed in the context of simplified protein models, can also be used to describe the folding in more realistic models.

Computer Simulation↗

PubMed1999

Chiral recognition of cellulose tris(5-fluoro-2-methylpheylcarbamate) toward (R)- and (S)-1, 1'-bi-2-naphthol detected by negative ion fast-atom bombardment mass spectrometry

Chiral recognition between cellulose tris(5-fluoro-2-methylphenylcarbamate) (MW > 120,000) as a host compound and (R,S)-1,1'-binaphthol (MW 286) as a guest compound was investigated by fast-atom bombardment mass spectrometry (FAB-MS). The use of negative ion FAB-MS made it possible to obtain a very simple mass spectrum of the guest compound with a high signal-to-noise ratio. Additionally, when nitrophenyl octyl ether, which has no OH group, was utilized as matrix, chiral recognition between the host and the guest compounds was unequivocally detected. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

PubMed1999

A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in rats.

The inhibitory effects of a Japanese herbal medicine, Chujo-to, on the progress of bone loss induced by ovariectomy in rats were investigated. Ovariectomized rats were administered with Chujo-to during weeks 7-14 after ovariectomy. At 14 weeks, the bone mineral density of the tibia from ovariectomized (OVX) rats had decreased by 27% compared with those in the sham-operated rats, and by a 18%-21% and 16% decrease after the administration of Chujo-to and 17 beta-oestradiol, respectively. The surface of a trabecular bone of the tibia in ovariectomized rats had a porous and fibrous appearance, while that of the same bone in sham-operated rats was composed of fine particles. After the administration of Chujo-to or 17 beta-oestradiol, the surface of trabecular bone maintained the porous and fibrous appearance. The uterine weight was not restored by Chujo-to but by 17 beta-oestradiol. These results suggest that Chujo-to has an efficacy on the osteoporosis of rats similar to 17 beta-oestradiol, but with a different mechanism.

Animals↗

PubMed1999

Chiral separations in capillary high-performance liquid chromatography and nonaqueous capillary electrochromatography using helically chiral poly(diphenyl-2-pyridylmethyl methacrylate) as chiral stationary phase.

Enantioseparations in nonaqueous capillary electrochromatography (CEC) are reported in this study for the first time, using wide-pore aminopropyl silica gel coated with helically chiral poly(diphenyl-2-pyridylmethyl methacrylate) (PDPM) as chiral stationary phase (CSP). The anodic electroosmotic flow (EOF) in a methanolic solution of ammonium acetate was used for the migration of neutral analytes through the packed bed in the capillaries. Four different techniques, high-performance liquid chromatography (HPLC) in common-size columns, capillary HPLC, pressure-assisted CEC and CEC were compared from the viewpoint of separation parameters. The latter three were performed with the same experimental setup, varying the relative contribution of the pressure-driven and the electrically driven flow to the overall mobility of the analyte. Capillary HPLC offers clear advantages compared to enantioseparations in common-size columns. However, for a given particle size of the packing material, CEC was not obviously advantageous compared to pressure-driven separations.

Chromatography, High Pressure Liquid↗

PubMed1999

Language supports for children's understanding of numerical fractions: cross-national comparisons.

This study examined Croatian, Korean, and U.S. children's knowledge of numerical fractions prior to school instruction. The research is part of an ongoing project examining the influence of language characteristics on mathematical thinking and performance. The part-whole quantitative relation denoted by numerical fractions may be easier to understand in East Asian languages like Korean. In these languages, the concept of fractional parts is embedded in the mathematics terms used for fractions. The results from this study suggest that the Korean vocabulary of fractions may influence the meaning 6- to 7-year-old children ascribe to numerical fractions and that this results in children being able to associate numerical fractions with corresponding pictorial representations prior to formal instruction.

Child↗

PubMed1999

Perioperative blood transfusion as a prognostic indicator in patients with hepatocellular carcinoma.

We studied the relation of perioperative blood transfusion and the outcomes in 175 patients with hepatocellular carcinoma (HCC) who underwent hepatic resection from 1986 to 1994 in our hospital. Hepatectomy was performed in 23 (13.1%) patients with and 152 (86. 9%) without blood transfusions. The cumulative cancer-free survival rates for patients who had received blood transfusion was significantly lower than that for patients who had not received blood transfusions (p = 0.003). Further examinations revealed a significant difference in cancer-free survival rates for stage I-II patients (n = 75) of HCC (p = 0.02) but not for stage III-IV patients (n = 56) (p = 0.06). Cox regression analysis for recurrence revealed that blood transfusion was the most significant prognostic indicator (p = 0.001) for recurrence in stage I-II patients but not in stage III-IV patients (p = 0.99). These results suggest that a perioperative blood transfusion may be a significant prognostic indicator for patients with HCC who had underwent hepatectomy, especially in stage I-II patients of HCC.

Adult↗

PubMed1999

The relationship of the platelet 5-HT-induced calcium response to clinical symptoms in eating disorders.

Clinical observations indicate that persons with eating disorders exhibit many psychopathologic symptoms such as difficulty with impulse control and depressed mood associated with impaired regulation of serotonin (5-HT) synaptic function in the central nervous system. In this study, we focused on the relationship between the 5-HT-induced calcium response in platelets and the clinical symptoms. While age, body weight, and severity of depressive symptoms were not correlated with 5-HT-induced response, there was an enhanced response in patients with bulimic symptoms or other impulsive behaviors. Moreover, patients with multi-impulsive behaviors had a significantly higher maximal increase than patients with uni-impulsive behavior, i.e., those who had only bulimic symptoms, as well as non-impulsive patients, and controls. Considering these results, the 5-HT-induced response may be related to difficulty with impulse control in general rather than bulimic eating attitudes specifically.

Adult↗

PubMed1999

Determination of age-related changes in human soluble interleukin 2 receptor in body fluids of normal subjects as a control value against disease states.

A highly sensitive enzyme-linked immunosorbent assay (ELISA) system was developed for human soluble interleukin-2 receptor (sIL-2R) with an ELISA-amplification system (ELAST((R))). The sensitivity of the new method was 20-fold higher than that without the amplification. Thus very low concentrations of sIL-2R in urine can be detected. With this method, serum and urine concentrations of sIL-2R were analyzed for healthy Japanese subjects with age 1-67 years. Mean sIL-2R concentrations in both serum and urine of children were significantly higher than those of adults. However, the concentrations of children showed a progressive decline to those of adults by the age of 15 years. There was no difference in the values between males and females. The results provide a control value of sIL-2R against those in disease states such as nephrotic syndrome. Since the trends in serum and urine were found to be similar, urinary sIL-2R measurement may provide sufficient information, without measuring the blood concentration.

Adolescent↗

PubMed1999

Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma.

The relationship between tumor angiogenesis and the expression of thymidine phosphorylase (dThdPase) in uterine cervical carcinoma tissues, as well as patient outcome, were investigated. Primary tumor specimens surgically obtained from 54 patients (stages Ib to IIIb) receiving neither chemotherapy nor radiation therapy before surgery were examined. Intratumoral microvessel density (IMVD) and dThdPase expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies and were correlated with clinicopathologic parameters and prognosis. IMVD for the 54 tumors ranged from 24.8 to 118.6, with a median value of 57.7 (number/0.7386 mm2/field). For immunoreactivity of dThdPase, 16 tumors were graded as -, 20 as 1+, and 18 as 2+. IMVD was significantly associated with the expression of dThdPase (P<.01). Both IMVD and dThdPase expression were well correlated with depth of myometrial invasion, endometrial invasion, and pelvic lymphnode metastasis (P<.05). Overall survival rates for 18 patients with strong dThdPase-staining tumors, assessed as 2+, were lower than those for 36 with weak dThdPase staining tumors (P = .0108). However, there was no statistical correlation between IMVD and patient outcome. The expression of dThdPase plays a role in the promotion of angiogenesis and affects the patient's survival in uterine cervical carcinomas.

Antigens, CD34↗

PubMed1999

New Monte Carlo algorithms for protein folding.

Over the past three decades, a number of powerful simulation algorithms have been introduced to the protein folding problem. For many years, the emphasis has been placed on how to both overcome the multiple minima problem and find the conformation with the global minimum potential energy. Since the new view of the protein folding mechanism (based on the free energy landscape of the protein system) arose in the past few years, however, it is now of interest to obtain a global knowledge of the phase space, including the intermediate and denatured states of proteins. Monte Carlo methods have proved especially valuable for these purposes. As well as new, powerful optimization techniques, novel algorithms that can sample much a wider phase space than conventional methods have been established.

Algorithms↗

PubMed1999

Immunohistochemical study of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor (FGF-R) in experimental squamous cell carcinoma of rat submandibular gland.

Fibroblast growth factor-2 (FGF-2) is a member of the heparin-binding growth factor family and has mitogenic activity. Immunohistochemical expression of FGF-2 and its receptor (FGFR) was evaluated in experimentally induced squamous cell carcinoma as well as transforming cells of rat submandibular gland (SMG) induced by 9,10-dimethyl-1,2-benzanthracene (DMBA)/sponge implantation. Proliferating cells detected by proliferating cell nuclear antigen (PCNA) staining during carcinogenesis were also compared with FGF-2 and FGFR stainings. In the normal SMG, FGF-2 and FGFR were present in the excretory, striated and intercalated duct cells. Pillar and transition cells of granular convoluted tubule (GCT) showed FGF-2 staining, PCNA-labeled cells in normal SMG were rarely observed. In 2-3 weeks after carcinogen implantation, the reactions of FGF-2 and FGFR were expressed in epithelial islands, duct-like structures and affected ductal segments. PCNA-positive cells were developed in these epithelial structures. In 4-8 weeks after carcinogen implantation squamous epithelium appeared surrounding DMBA/sponge and gradually transforming with high PCNA labeling in the based cells and strong staining of FGF-2 and FGFR. Squamous cell carcinoma arose within about 12 weeks of the experiment. In squamous cell carcinoma, there was an intense immunohistochemical expression of FGF-2 and FGFR. Basal and parabasal layers of the squamous cell carcinoma showed high PCNA labeling. FGF-2-positive cells were found in the connective tissue stroma and in inflammatory cells around the proliferating duct-like structure. Coexpression of FGF-2 and FGFR was indicated in transforming cells during carcinogenic processes and in experimental squamous cell carcinoma of rat SMG. These findings suggested that FGF may play an important role for squamous metaplasia and carcinogenesis in rat SMG as an autocrine factor and FGF-positive stromal cells may also act to stimulate epithelial proliferation.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

Electrostatic effects on the alpha-helix and beta-strand formation of BPTI(16-36) studied by Monte Carlo simulated annealing.

The electrostatic effects on the secondary structure forming tendencies of a peptide fragment with residues 16-36 of bovine pancreatic trypsin inhibitor, BPTI(16-36), are studied using Monte Carlo simulated annealing simulations. We consider three dielectric functions epsilon(r) of distance r: constant dielectric function (epsilon = 2; strong electrostatic interactions) and sigmoidal functions varying from epsilon(0) = 2 to epsilon(infinity) = 47 (intermediate) and to epsilon(infinity) = 78 (weak). Simulations with epsilon = 2 suggest that this peptide exhibits a significant propensity for beta-strand formations in accordance with a beta-sheet structure of the relevant segment in native BPTI. The tendency for alpha-helix formations becomes almost comparable with that of beta-strands in the simulation with epsilon(infinity) = 47, and there appears no appreciable conformational propensity for this case. Finally, the results with epsilon(infinity) = 78 generate low-energy conformations with conspicuous alpha-helices. These findings suggest the possibility that the change in electrostatic interactions can be the key factor for the conformational transitions of peptides between alpha-helix and beta-sheet that have recently been observed in experiments. These changes in electrostatic interactions can arise from those in various environmental factors such as conformations of the rest of the protein molecule and solvent conditions.

Algorithms↗

PubMed1999

Activation of three types of voltage-independent Ca2+ channel in A7r5 cells by endothelin-1 as revealed by a novel Ca2+ channel blocker LOE 908.

1. We have shown that in addition to voltage-operated Ca2+ channel (VOC), endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channel (NSCC) in A7r5 cells: its lower concentrations (< or = 1 nM; lower [ET-1]) activate only an SK&F 96365-resistant channel (NSCC-1), whereas its higher concentrations (> or = 10 nM; higher [ET-1]) activate an SK&F 96365-sensitive channel (NSCC-2) as well. 2. We now characterized the effects of a blocker of Ca2+ entry channel LOE 908 on NSCCs and store-operated Ca2+ channel (SOCC) in A7r5 cells, and using two drugs, clarified the involvement of these channels in the ET-1-induced increase in the intracellular free Ca2+ concentrations ([Ca2+]i). Whole-cell recordings and [Ca2+]i monitoring with fluo-3 were used. 3. LOE 908 up to 10 microM had no effect on increases in [Ca2+]i induced by thapsigargin or ionomycin, but SK&F 96365 abolished them. 4. In the cells clamped at -60 mV, both lower and higher [ET-1] induced inward currents with linear iv relationships and the reversal potentials of -15.0 mV. Thapsigargin induced no currents. 5. In the presence of nifedipine, lower [ET-1] induced a sustained increase in [Ca2+]i, whereas higher [ET-1] induced a transient peak and a sustained increase. The sustained increases by lower and higher [ET-1] were abolished by removal of extracellular Ca2+, and they were suppressed by LOE 908 to 0 and 35%, respectively, with the LOE 908-resistant part being abolished by SK&F 96365. 6. These results show that LOE 908 is a blocker of NSCCs without effect on SOCC, and that the increase in [Ca2+]i at lower [ET-1] results from Ca2+ entry through NSCC-1 in addition to VOC, whereas the increase at higher [ET-1] involves NSCC-1, NSCC-2 and SOCC in addition to VOC.

Acetamides↗