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Biomedical subjects

Y Shimada

Publications and source records attributed to Y Shimada.

At least 541 records · Page 30Linked to original sources
PubMed1991

[A case report of liver metastasis from rectal cancer effectively treated with intravenous infusion of cisplatin alone].

A 49-year-old man with liver metastasis from rectal cancer was treated with cisplatin (CDDP) alone. Cisplatin was administered intravenously 3 times at a dose of 50 mg (31 mg/m2). He achieved an excellent PR (94% decrease) as determined by CT scanning, and plasma CEA level decreased from 37 to 2.2 ng/ml. The side effects were nausea, vomiting, and reflux esophagitis, but neither leucopenia nor renal dysfunction was observed. As a result, a radical operation could be undertaken.

Adenocarcinoma↗
PubMed1990

Progressive inactivation of the expression of an erythroid transcriptional factor in GM- and G-CSF-dependent myeloid cell lines.

The transcriptional binding protein NFE-1 (also called GF-1 and Ery-f1) is thought to play a necessary, but not sufficient, role in the regulation of differentiation-related gene expression in a subset of hematopoietic lineages (erythroid, megakaryocytic, and basophil-mast cell). In order to clarify the mechanism which underlies the lineage-specificity of the NFE-1 expression, as well as the relationship between the expression of this factor and growth factor responsiveness, we have evaluated the capacity of erythropoietin (Epo)-, granulomonocytic (GM)-colony stimulating factor (CSF)-, and granulocyte (G)-CSF-dependent subclones derived from the interleukin 3 (IL-3)-dependent cell line 32D, to express 1) NFE-1 mRNA, 2) NFE-1-related nuclear proteins, and 3) chloramphenicol acetyl transferase (CAT) activity when transfected with a CAT gene under the control of NFE-1 cognate sequences. NFE-1 mRNA was found to be expressed not only in cells with mast cell (IL-3-dependent 32D) and erythroid (Epo-dependent 32D Epo1) phenotypes, but also in cells with predominantly granulocyte/macrophage properties, such as the GM-CSF- (early myelomonocytic) and G-CSF- (myelocytic) dependent subclones of 32D. However, a gradient of expression, correlating with the lineage, the stage of differentiation, and the growth factor responsiveness of the cell lines, was found among the different subclones: Epo greater than or equal to IL-3 greater than GM-CSF greater than G-CSF. Binding experiments demonstrated NFE-1 activity in all cell lines except the G-CSF-dependent line. Function of the NFE-1 protein was assessed by the expression of the CAT gene linked to the SV40 promoter and a mutant (-175 T----C) HPFH gamma-globin promoter. High level CAT expression was seen only in the Epo1 cells although low level expression was also seen in the parent 32D. These results demonstrate that the specificity of the expression of NFE-1 for the erythroid--megakaryocytic--mast cell lineages is obtained by progressive inactivation of its expression in alternative lineages.

Animals↗
PubMed1990

Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

Tissue selectivity of pravastatin sodium (pravastatin) in inhibition of cholesterol synthesis was investigated and its effect was compared with other 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, such as lovastatin, simvastatin and ML-236B. Inhibition of cholesterol synthesis in vivo was measured by incorporation of radioactivity into the sterol fraction 1 h after intraperitoneal injection of [14C]acetate to mice. The drugs were orally administered to mice 2 h before the acetate injection. When pravastatin at a dose of 20 mg/kg was administered to mice, about 90% inhibition of cholesterol synthesis was observed in liver and ileum, but the inhibition was less than 14% in kidney, spleen, adrenal, testis, prostate and brain. This tissue selectivity of pravastatin was also demonstrated even in varying doses (5-100 mg/kg) and time (75-180 min) after drug administration. Other 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors did not show such a tissue-selective inhibition of sterol synthesis under the same conditions. These results obtained with the in vivo study were confirmed in vitro by the inhibition of sterol synthesis in various cultured cells and rats lenses, as well as by cellular uptake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

Acetates↗
PubMed1990

Apoptosis of vascular endothelial cells by fibroblast growth factor deprivation.

Survival and proliferation of many types of vascular endothelial cells are influenced by fibroblast growth factor (FGF)1. Removal of FGF from the medium of human umbilical vein endothelial cells (HUVEC) in culture resulted in death of the cells. Here we show that the death caused by deprivation of FGF is active death or apoptosis, and the process of apoptosis can be inhibited by cycloheximide, an inhibitor of protein synthesis. The present study shows apoptosis occurs in endothelial cells in culture. The process of active death of vascular endothelial cells is inhibited by growth factor. This mechanism may be important for the regulation of vascular organization through the degeneration of vessels.

Animals↗
PubMed1990

Changes in phospholipid composition and phospholipase D activity during the differentiation of Physarum polycephalum.

Changes in phospholipid composition and phospholipase D activity were observed during a differentiation from haploid myxoamoebae to diploid plasmodia of a true slime mold, Physarum polycephalum. In the amoeboid stage, the main components of phospholipid fraction were phosphatidylethanolamine (PE, 43.3%), phosphatidylcholine (PC, 28.8%) and phosphatidylinositol (PI, 8.0%), but in the plasmodial stage, PC was dominant (40.7%) and other main components were PE (31.5%) and phosphatidic acid (PA, 11.0%). The specific activity of phospholipase D in the plasmodia was 5.7-times higher than that in the myxoamoebae when measured in the presence of Ca2+ at the alkaline pH. In the amoeboid stage, phospholipase A activity (A1 or A2) was detected at the alkaline pH with Ca2+. Phospholipase D activity in the plasmodia was characterized: pH optimum was 6.0; Ca2+ was required for the reaction and Ba2+ could substitute partly for Ca2+; PE was the best substrate for the hydrolytic activity and PC and PI were not appreciably hydrolyzed; and all detergents tested inhibited the enzyme activity.

Calcium↗
PubMed1990

Growth-inhibiting effect of tumor necrosis factor on human umbilical vein endothelial cells is enhanced with advancing age in vitro.

We have examined the effects of in vitro aging on the growth capacity of human umbilical vein endothelial cells (HUVECs) under the influence of tumor necrosis factor (TNF) with or without interferon-gamma (IFN-gamma). The growth and colony-forming abilities of control cells were impaired with advancing age in vitro, especially at later stages (more than 70-80% of life span completed). It was found that treatment with TNF inhibited growth and colony-forming efficiency at any in vitro age. The effects of TNF were shown to increase with increasing in vitro age, as reflected by a more pronounced increase in doubling times, a decrease in saturation density, and a reduction in colony-forming efficiency. However, the characteristics of TNF receptors, including the dissociation constant, and the number of TNF-binding sites per cell-surface area remained rather constant. The effect of TNF was augmented by IFN-gamma at a dose that alone affected growth and colony formation only slightly. The augmentation by IFN-gamma was also found to depend on in vitro age; the synergy with TNF in the deterioration of colony-forming ability was observed only in "aged" cells. These results suggest that the intrinsic responsiveness of HUVECs to growth-inhibiting factors, as well as to growth-stimulating factors, changes during aging in vitro.

Aging↗
PubMed1990

Assembly of connectin (titin) in relation to myosin and alpha-actinin in cultured cardiac myocytes.

By using polyclonal and monoclonal antibodies against connectin (titin) which stain the A-I junctional area and the A-band domain (polyclonal anti-connectin and monoclonal 4C9) and the I-band domain (monoclonal SM1), the developmental relationship of this elastic protein with sarcomeric proteins, especially and alpha-actin, was examined in embryonic chick cardiac myocytes in vitro under fluorescence microscopy. During premyofibril stages, I-Z-I proteins were detected first (alpha-actinin dots and diffuse actin [phalloidin and anti-troponin C] staining), and later in these areas connectin and myosin dots appeared with nearly identical distribution. Somewhat later, phalloidin-positive nonstriated fibrils were observed in a straight course. They were always reactive with antibodies against alpha-actinin and troponin C, but unreactive or only weakly reactive with anticonnectin and anti-myosin. Initially, alpha-actinin dots were aligned along these fibrils but did not form striations. As they aggregated to form Z-bands, connectin and myosin started to exhibit typical striation ('doublets' and A-bands, respectively). No difference in the staining pattern was observed with two kinds of monoclonal antibodies against different domains of connectin filaments (4C9 and SM1) at early phases. As myosin staining began to show clear A-bands, connectin epitopes became arranged in polarized positions. We conclude that primitive I-Z-I complexes appear prior to the assembly of connectin and myosin filaments and then connectin filaments, developing intimately and coordinately with myosin, become associated with the alpha-actinin lines. Thus it appears that the putative elastic protein connectin plays some role in integrating myosin filaments with the preexisting I-Z-I brushes. The occasional absence of connectin and A-bands between two Z-bands, beyond both of which clear sarcomeres have been formed, indicates that connectin is not a preformed scaffold of myofibrils on which sarcomeric proteins accumulate.

Actinin↗
PubMed1990

Clinical significance of monitoring serum levels of 5-fluorouracil by continuous infusion in patients with advanced colonic cancer.

Serum concentrations of 5-fluorouracil (5-FU) given by continuous infusion to 19 patients with advanced colonic cancer were measured by an HPLC method, and steady-state concentration (SSc), area under the curve (AUC72) and total body clearance (Cl) were calculated as pharmacokinetic parameters. The serum level of 5-FU rapidly increased, reaching a plateau within 2 h after the start of administration. There were positive correlations between the dose and both SSc (r = 0.578, P less than 0.01) and AUC72 (r = 0.558, P less than 0.05). When the patients were divided into toxic and non-toxic groups according to the degree of toxicity, the values for SSc and AUC72 in the toxic group were significantly higher than those in non-toxic patients. The Cl value in the toxic group was also significantly different from that in the non-toxic group when data were calculated on a log scale. Furthermore, no differences in these parameters between effective and non-effective in these parameters between effective and non-effective groups were detected when the patients were divided into two groups according to anti-neoplastic responses. These results indicate that increased serum concentration does not always provide therapeutic benefits to patients receiving continuous infusions of 5-FU.

Adult↗
PubMed1990

Tumor necrosis factor reduces lifespan of human endothelial cells in vitro.

Tumor necrosis factor (TNF) is known to regulate the proliferation and function of vascular endothelial cells (ECs). We have examined the effects of TNF on the growth and aging of human ECs of different origins and compared them with those in human normal diploid fibroblasts. The results obtained were as follows: (1) TNF reduces the growth rate and in vitro life span of ECs in both dose- and treatment length-dependent fashions; (2) ECs are significantly more sensitive to TNF than fibroblasts; and (3) the life span shortening effect of TNF on ECs increases as a function of in vitro cell age. These results suggest that the aging of ECs is modified by TNF exposure.

Cell Division↗
PubMed1990

Separation and characterization of two molecular forms of Geotrichum candidum lipase.

Southern blot analysis of the Geotrichum candidum genome with a cloned lipase cDNA as the probe indicated the existence of two genes on the chromosome of the fungus which are homologous to the cDNA. As expected, two forms of lipase (lipases I and II) were actually isolated by hydrophobic interaction chromatography after a multistep procedure including ammonium sulfate fractionation, anion exchange chromatography, and gel filtration of the culture filtrate. Lipase I, the first eluted fraction, was the predominant form, and more than 80% of the total activity was attributed to this form. Amino acid sequence analysis of the amino and carboxyl termini of these two enzyme preparations indicated that lipase I was the product of the lipase gene whose cDNA had previously been cloned and sequenced [Shimada et al. (1989) J. Biochem. 106, 383-388]. Lipase II, on the other hand, had similar amino acid composition, but different terminal sequences which were not found in the primary structure of lipase I deduced from the cDNA sequence. These results gave lines of evidence for the expression of truely different lipase genes and ruled out the possibility that the observed multiple forms are caused by proteolytic digestion. The molecular mass estimated by SDS-PAGE and the isoelectric point of lipase I were 64 kDa and 4.3, while those of lipase II were 66 kDa and 4.3, respectively. The two lipases had essentially the same specific activities, substrate specificities, pH stabilities, and optimal temperatures, but different pH optima and thermal stabilities.

Amino Acid Sequence↗
PubMed1990

cDNA cloning and characterization of Geotrichum candidum lipase II.

Geotrichum candidum produces two extracellular lipases, I and II. A lipase II cDNA clone was isolated from a cDNA library by colony hybridization using the 32P-labeled fragment of lipase I cDNA isolated previously. The nucleotide sequence of lipase II cDNA determined by the dideoxy chain terminating method includes the N- and C-terminal amino acid sequences of lipase II, and the overall amino acid composition deduced from the cDNA coincides with that deduced on amino acid analysis of this protein. The cloned lipase II cDNA codes a protein of 544 amino acids and a part of the signal sequence of 13 amino acids. The peptide chain lengths of lipases I and II are the same, their overall identity being 84%. Furthermore, four Cys residues are completely conserved, which may participate in the formation of disulfide bridges. A homology search indicated that the G. candidum lipases and Candida cyclindracea lipase are homologous enzymes and that they are members of the cholinesterase family.

Amino Acid Sequence↗
PubMed1990

Pilot phase II study of cis-diamminedichloroplatinum (II) against metastatic gastric cancers.

Fifty patients with metastatic gastric cancer were entered for a phase II study of Cis-diamminedichloroplatinum (II) (CDDP), 45 of whom were able to have their responses evaluated. CDDP was given intravenously at a dose of 80 mg/m2 over two hours every three weeks. There were four partial responses (25%) among the 16 patients who had had no prior chemotherapy, and three partial responses (10%) among the 29 patients who had had prior chemotherapy. The total response rate was 16%. The chief manifestations of toxicity were gastrointestinal symptoms, such as nausea and/or vomiting. Severe nephrotoxicity was not observed. From these data, the administration of CDDP at a dose of 80 mg/m2 every three weeks was considered tolerable, and CDDP as a single agent was considered effective against metastatic gastric cancers. In addition, three of the 29 pretreated patients who responded suggested that CDDP could be given as a second-line chemotherapy when initial treatment with other active agents, i.e. fluorinated pyrimidine or mitomycin C, fails to obtain a response.

Adult↗
PubMed1990

Effect of acute changes in renal arterial blood flow on urine oxygen tension in dogs.

The relationships between urine oxygen tension (PuO2), PaO2, and acute changes in renal arterial blood flow (RBF) were studied in 19 anesthetized dogs. Indwelling sensors that measure continuously PO2 were inserted into the femoral artery and the ureter. RBF was measured by an electromagnetic flowmeter placed over the renal artery. PuO2 increased significantly from 36 to 72 torr during a stepwise increase in PaO2 from 70 to 180 torr. RBF was decreased in a stepwise fashion from a baseline value of 5.51 to 4.16, 2.13, and finally to .20 ml/kg.min by aortic constriction. PuO2 decreased significantly from a baseline value of 72 torr to 66, 57, and finally to 23 torr. The correlation coefficient between RBF and PuO2 was .84, which was significantly higher than that between RBF and femoral arterial pressure or that between RBF and urinary flow rate. This study demonstrates that PuO2 is a sensitive indicator of acute RBF changes in normal, healthy dogs.

Animals↗
PubMed1990

Unresponsiveness of insulinoma cells to secretin: significance of the secretin test in patients with insulinoma.

It is well known that B cells in the pancreas release insulin when stimulated by secretin, but there have been few reports on the response of insulinoma cells to secretin. In five patients with insulinoma, changes in serum immunoreactive insulin (IRI) concentration were measured after the intravenous injection of secretin into the peripheral vein before and after extirpation of the insulinoma. The extirpated insulinomas were cultured and tested for their response to secretin. The rise in serum IRI in response to secretin in patients with insulinoma was significantly slower and smaller than in normal volunteers. After removal of the insulinoma, the response to secretin became prompt and increased with time. Cultured insulinoma cells did not release insulin when stimulated by secretin. Therefore, it is concluded that the response of insulinoma cells to secretin is quite different from that of normal beta cells, and that the function of beta cells in the insulinoma-bearing pancreas is suppressed by the autonomous hypersecretion of insulin by the insulinoma. The extent of the decrease in function of the beta cells in patients with insulinoma can be estimated by the intravenous secretin test. Thus, the secretin test is sometimes useful in the differentiation of hypoglycemia due to insulinoma from that due to beta cell hyperplasia or alimentary hyperinsulinemia.

Adenoma, Islet Cell↗
PubMed1990

Synergistic effect of cyclosporin A and verapamil in overcoming vincristine resistance of multidrug-resistant cultured human leukemia cells.

Reversal of vincristine (VCR) resistance by cyclosporin A (CyA) or the combination of CyA and verapamil (VER) was investigated by using four P-glycoprotein (P-gp)-associated human multidrug-resistant (MDR) cell lines (K562/ADM, KYO-1, HEL and CMK). Drug sensitivity was expressed as 50% inhibitory concentration (IC50). The degree of reversal of resistance was expressed as x-fold decrease by dividing the IC50 value without modifier(s) by that with modifier(s). CyA overcame P-gp-associated MDR significantly in all four MDR cell lines. Reversal of VCR resistance by CyA appeared to be dose-dependent. In the case of low-grade MDR cell lines (KYO-1, HEL and CMK), CyA at the low concentration of 0.5 microgram/ml was still effective. The degree of reversal of VCR resistance in this condition was greater (6.3- to 16-fold decrease) in the low-grade MDR cell lines than in a high-grade MDR cell line (K562/ADM) (2.9-fold decrease). At a high concentration (5 micrograms/ml) of CyA, however, it was greater (240-fold decrease) in the high-grade MDR cell lines than in the low-grade MDR cell line (20- to 100-fold decrease). This indicates that concentration of CyA required for overcoming drug resistance in MDR cells was dependent on the degree of drug resistance. CyA overcame VCR resistance more efficiently than VER. The combination of CyA and VER enhanced reversal of VCR resistance in a supra-additive or at least an additive manner and overcame VCR resistance at low concentrations of both modifiers that are clinically achievable with safety.

Cyclosporins↗