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E Araki

Publications and source records attributed to E Araki.

At least 91 records · Page 5Linked to original sources
PubMed1991

Expression of Alzheimer amyloid beta-protein precursor gene in neuronal cells.

Five forms of Alzheimer amyloid beta-protein precursors (APP or BPP) have been found. Among them, APP695 is predominantly found in neuronal cells and may be involved in some neuronal functions. In the present work, we investigated the relationship between the APP expression and the formation of neurites, a typical neuronal morphology, by measuring the amounts of three major APP mRNAs in PC12 cells, using the polymerase chain reaction. In PC12 cells, nerve growth factor which induced a neurite formation, enhanced the expression of APP695. The ratio of APP695 to APP770 increased 2.6-fold after 6 days of treatment. Cyclic AMP also induced a similar morphological change, but did not affect the APP expression pattern. Thus, the neuronal expression of the APP gene is not directly related with neurite formation. We have also identified cis-elements for the neuronal expression of APP gene.

Alzheimer Disease↗
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

[Fifty two-week chronic oral toxicity study of mofezolac (N-22) in beagle dogs].

The chronic toxicity study of mofezolac (N-22), a new developed analgesic and anti-inflammatory agent, was carried out in beagle dogs by oral administration of the test compound at dose levels of 1, 3, 6 and 12 mg/kg once daily for 52 weeks. The recovery study was also carried out by withdrawal for 5 weeks. 1. No death occurred during the administration and recovery periods in all groups, there were no abnormal findings due to N-22 administration on behavior and appearance, body weight and food consumption. 2. There were no abnormal findings due to N-22 administration on fecal test, urinalyses, hematological and biochemical examinations, hepatic and renal function tests, ophthalmological examination, electrocardiography, blood pressure and organ weight. 3. By histopathological examination, loss of villi in small intestine was found in one female of 6 mg/kg group, erosion in small intestine in one male of 12 mg/kg group, and shortening of villi and ulcer in small intestine in each one female of 12 mg/kg 4. Accordingly, the non-effective dose levels of N-22 were estimated to be 6 mg/kg for male and 3 mg/kg for female in this study.

Administration, Oral↗
PubMed1989

Enhanced antitumor effect of 5'-deoxy-5-fluorouridine by oral administration with L-cysteine.

When given orally in combination with L-cysteine, 5'-deoxy-5-fluorouridine (DFUR) brought about a significant reduction in the growth of adenocarcinoma 755 and a significant prolongation of life-span in mice bearing Lewis lung carcinoma without increased toxicity to the host as compared with DFUR alone, though L-cysteine alone did not show an appreciable antitumor activity. Moreover, the combination of DFUR and L-cysteine resulted in a marked retardation of growth of human colon tumor LS174T transplanted into nude mice. Thus, the potency of DFUR was increased by L-cysteine. Pharmacokinetic studies revealed that after DFUR administration, plasma DFUR and 5-fluorouracil (5-FU) levels rapidly declined, but that, in the combination with L-cysteine, the plasma clearances of DFUR and 5-FU were slowed down considerably. In the tumor, DFUR and 5-FU levels were similar to those in the plasma. Such a prolongation of DFUR and 5-FU levels in plasma and tumor may produce the enhancement of antitumor effect seen with the combination of DFUR and L-cysteine.

Adenocarcinoma↗
PubMed1989

Persistence and expression of circular DNAs encoding Drosophila amylase, bacterial chloramphenicol acetyltransferase, and others in Xenopus laevis embryos.

We injected circular forms of several different DNAs into fertilized eggs of Xenopus laevis, and studied the persistence and expression of the injected DNAs during early embryonic development. When we injected plasmids which contained Drosophila amylase genes, the copy number of the injected DNA increased only slightly during cleavage, started to decrease at the blastula stage, then became very small at the tadpole stage. In such embryos, Drosophila amylase activity was detected at and after the gastrula stage. When we injected other kinds of circular DNAs (pX1r101A, cDm2055, pII25.1, pBR322, and pSP-64-L14), their copy number did not increase throughout the early stages. When circular plasmids that contained bacterial chloramphenicol acetyltransferase (CAT) genes were injected, their copy number usually did not increase, but sometimes, for unknown reasons, it increased extensively throughout the blastula to gastrula stages. In both cases, CAT enzyme activity started to be expressed during the blastula to gastrula stages and disappeared at the 2 day-old tadpole stage. The level of CAT enzyme activity was roughly proportional to the amount of CAT mRNA formed, and also to the copy number of injected genes. From these results, we concluded that in Xenopus embryos, exogenously-injected circular DNAs are preserved for the most part as circular DNAs, and that the increase in their copy number within the embryos is not prerequisite for the expression of their genetic information.

Amylases↗
PubMed1989

Hemoglobin Hope found in a patient with basal cell carcinoma of the genial region.

Hemoglobinopathy was detected in a 72-year-old female with basal cell carcinoma of the genial region during high-performance liquid chromatography of hemolysate for the assay of HbA1c. Structural analysis demonstrated that this abnormal hemoglobin was identical to Hb Hope [beta 136(H14)Gly----Asp]. No clinical or hematological abnormality was observed. A study of the family revealed that a younger sister and two sons of the propositus had the same hemoglobin variant. This is the second observation of Hb Hope in a Japanese family.

Aged↗
PubMed1989

[Quantitative assessment of myocardial viability following coronary artery bypass grafting using exercise thallium-201 myocardial single photon emission computed tomography and left ventricular regional wall motion].

Using exercise thallium-201 myocardial single photon emission computed tomography (SPECT) and % radial shortening (%RS), 58 patients were evaluated before and after coronary artery bypass grafting (CABG) to quantitatively assess myocardial viability and the effect of CABG. The patient was classified, according to redistribution pattern, as group I with only complete redistribution (20 cases) and group II with including incomplete redistribution (22 cases) and group III with no redistribution (16 cases). 1. Group I was expected complete improvement of ischemic myocardium after CABG but regional left ventricular wall motion was unchanged (sigma i%RS: 142.5 +/- 54.7----138.4 +/- 39.6, sigma a%RS: 201.2 +/- 51.1----238.2 +/- 68.2). 2. Group II was expected to diminish ischemic size after CABG and left ventricular regional wall motion was significantly improved (sigma i%RS: 68.8 +/- 25.9----154.9 +/- 42.6 p less than 0.01, sigma a%RS: 108.4 +/- 62.3----178.9 +/- 77.6, p less than 0.05). 3. Group III was no significant change of ischemic size and left ventricular wall motion after CABG (sigma i%RS: 67.8 +/- 24.1----83.9 +/- 19.2, sigma a%RS: 86.0 +/- 29.0----94.0 +/- 33.9). The present study suggests that quantitative assessment of myocardial viability using exercise thallium-201 myocardial SPECT and %radial shortening was useful method to determine the indication and to assess the effect of CABG.

Adult↗
PubMed1989

[The effects of aorto-coronary bypass grafting on left ventricular diastolic function in patients with left ventricular dysfunction].

To determine the effects of aorto-coronary bypass grafting on left ventricular diastolic function in patients with low ejection fraction (EF less than or equal to 0.40), 17 patients were studied. They were divided into two groups, Group I: 8 patients without previous myocardial infarction, Group II: 9 patients with previous myocardial infarction. Left ventricular diastolic function was assessed by maximum negative dp/dt, constant T, diastolic compliance and 1/3 functional filling. In conclusions, when ejection fraction is depressed (EF less than or equal to 0.40), myocardial revascularization improves left ventricular diastolic function in patients without previous myocardial infarction, but not with previous myocardial infarction.

Aged↗
PubMed1989

[Quantitative analysis of myocardial revascularization on left ventricular diastolic function].

To evaluate the effects of myocardial revascularization on left ventricular diastolic function, we studied three groups of subjects. Group I consisted of 10 patients without any previous myocardial infarction. Group II consisted of 10 patients with previous myocardial infarction. The control group consisted of 8 normal subjects, all with no evidence of cardiac disease as determined by cardiac catheterization. Left ventricular diastolic function was assessed by maximum negative dp/dt, constant T, diastolic compliance and 1/3 fractional filling before and after surgical revascularization. (1) Constant T, maximum negative dp/dt and diastolic compliance: There was no significant difference among groups I, II and the control group preoperatively, and the variables were not improved postoperatively. (2) 1/3 fractional filling: 1/3 fractional fillings in groups I and II were significantly lower (p less than 0.05, p less than 0.01) than the control group preoperatively, and it was significantly improved in group I, but unchanged in group II postoperatively. In conclusion, myocardial revascularization improves left ventricular diastolic function in the patients without previous myocardial infarction. The effects of myocardial revascularization, however, in the patients with prior myocardial infarction do not bring about an enhancement of left ventricular diastolic function.

Adult↗
PubMed1988

[Inhibitory effects of somatostatin analog (SMS 201-995) on pancreatic hormones in patients with malignant islet-cell carcinoma].

Acute effects of somatostatin analog (SMS 201-995) on pancreatic hormones were studied in two patients with malignant islet-cell carcinoma. Before and after subcutaneous injection of somatostatin with a doses of 50 micrograms, blood glucose (BG), serum growth hormone (hGH), C-peptide immunoreactivity (CPR), plasma immunoreactive glucagon (IRG) and gastrin were assayed, and changes in elution patterns of IRG and gastrin were also analyzed on Bio-Gel P-30 column chromatography. In Patient 1 with glucagonoma syndrome and hypergastrinemia, a prompt and remarkable decrease in plasma IRG and gastrin was observed after the injection of SMS 201-995 in association with a decrease in blood glucose, and then IRG and gastrin increased gradually. The suppressive effect continued for at least 6 hours. On gel filtration of the plasma obtained before the injection of the analog, three major peaks, greater than 20000, 9000 and 3500 molecular-weight (mol wt) fractions, were seen in IRG fraction. The decrease in plasma IRG observed at 1 hour after the injection was mainly due to a marked decrease in the 3500 molecular weight fraction. In addition, a slight decrease in the 9000 mol wt fraction was seen. At 4 hours after the injection, the 3500 mol wt peak returned to the previous level, while the 9000 mol wt peak decreased further. On the other hand, the gastrin elution pattern of plasma obtained before the injection revealed three major gastrin peaks, greater than 20000, 7000 and 5000 mol wt fraction. The changes in the gastrin elution pattern after the injection were similar to those of the IRG elution pattern. In Patient 2 with Zollinger-Ellison's syndrome, the plasma gastrin level decreased gradually for 5 hours after the injection. On gel filtration of the plasma obtained before the injection, two major gastrin peaks, 7000 and 5000 mol wt fraction, of which the large-molecular fraction was more prominent than the small-molecular fraction, were observed. After the injection, a marked decrease in the small-molecular fraction and a gradual decrease in the large-molecular fraction were observed for 4 hours, accompanied by a decrease in plasma gastrin. At 7 hours after the injection, the smaller fraction was augmented again. The serum CPR and hGH was slightly suppressed after the injection in both patients. The adverse effects of slight nausea and vomiting were noticed only in Patient 1.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma, Islet Cell↗
PubMed1988

Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5-fluorouracil against adenocarcinoma 755 in mice. Increased therapeutic index and correlation with increased plasma 5-fluorouracil levels.

A marked inhibition of the growth of solid tumor adenocarcinoma 755 was achieved by the combination of 5-fluorouracil (5-FU) with bromovinyldeoxyuridine (BVDU). The therapeutic index (LD50/ED50) for the combination of BVDU plus 5-FU was 8.1 and 3.9 upon intraperitoneal (i.p.) or oral (p.o.) administration, respectively. The therapeutic index of i.p. 5-FU given alone was 2.3, whereas for p.o. 5-FU given alone no therapeutic index could be established because of insufficient activity of the compound. Thus, the therapeutic index of 5-FU increased significantly when combined with BVDU. Pharmacokinetic studies revealed that upon i.p. or p.o. 5-FU administration plasma 5-FU levels rapidly declined, but that, in the combination with BVDU, the plasma clearance of 5-FU, especially following p.o. administration, was slowed down considerably. Antitumor activity of 5-FU correlated with AUC (area under the concentration x time curve), within the plasma 5-FU concentration range from 0.02 to 0.4 microgram/ml.

Adenocarcinoma↗
PubMed1987

Characterization of the promoter region of the human insulin receptor gene. Evidence for promoter activity.

Recombinant clones containing the promoter region of the human insulin receptor gene were isolated from genomic libraries derived from nondiabetic persons. A 1.5-kilobase pair fragment of the 5'-flanking region was sequenced. One transcriptional start site, located at 203 bases upstream from the start of translation was identified by nuclease S1 mapping and the primer extension experiment using the human insulin receptor mRNA. The bacterial chloramphenicol acetyltransferase assay revealed that a 573-base pair fragment immediately preceding the ATG has promoter activity and that the transcript initiates from the normal start site of the insulin receptor gene in the COS cells. The promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G + C content, and contains seven central components of potential Sp 1 binding sites (GGGCGG or CCGCCC). These features are common to those found in the regulatory regions of a class of constitutively expressed "housekeeping" genes. A comparison between the promoter sequence of the human insulin receptor and those of other "housekeeping" genes revealed the presence of homologous sequences among these genes, in addition to the potential Sp 1 binding sites.

Base Sequence↗
PubMed1987

Replacement of lysine residue 1030 in the putative ATP-binding region of the insulin receptor abolishes insulin- and antibody-stimulated glucose uptake and receptor kinase activity.

To test whether the tyrosine kinase activity of the insulin receptor is crucial for insulin action, we have constructed mutations of the human insulin receptor at Lys-1030, which is in the presumed ATP-binding region. By using oligonucleotide-directed mutagenesis, this lysine residue was replaced with either methionine, arginine, or alanine. Chinese hamster ovary cells were transfected by mutant cDNAs and the expressed insulin receptors were characterized. We show here that none of these mutants exhibited insulin-activated autophosphorylation and kinase activity in vitro. They also do not mediate insulin- and antibody-stimulated uptake of 2-deoxyglucose. The tyrosine kinase activity is thus required for a key physiological response of insulin.

Adenosine Triphosphate↗
PubMed1987

Recombinant human tumor necrosis factor depresses serum iron in mice.

Recently many findings about the physiological and biochemical functions of recombinant human tumor necrosis factor (rHu-TNF) have been reported. In the present study, the effect of rHu-TNF on serum iron in C3H/HeN and C57BL/6 mice was determined. Blood samples were obtained before intravenous injection of rHu-TNF, and also at various times after the injection. Results from five experiments showed that the serum iron was depressed between 1/3 to 1/5 of that of untreated mice 4 to 24 h after injection of 5 or 10 micrograms of rHu-TNF. The low level persisted for 33 h, rebounded at 48 to 72 h, and returned to normal by 96 h after the injection. Serum iron was determined by the colorimetric method using the sensitive reagent, ferrozine (3-(2-pyridyl)-5,6-bis(4-sulfophenyl)-1,2,4-triazine. We believe that this is the first report of depression of serum iron in mice by intravenous injection of rHu-TNF. The physiological role of repressed serum iron in the in vivo response to TNF remains to be established.

Animals↗