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Biomedical subjects

E Fukuda

Publications and source records attributed to E Fukuda.

At least 19 recordsLinked to original sources
PubMed2004

Expression of Tie-1 and 2 receptors, and angiopoietin-1, 2 and 4 in gastric carcinoma; immunohistochemical analyses and correlation with clinicopathological factors.

AIMS: There is strong evidence that tyrosine kinases are involved in the regulation of tumour progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, and among them Tie-1 and 2 constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of the Tie-2 tyrosine kinase receptor. The aim of this study was to determine the expression profile of Tie-1 and 2 and Ang-1, 2 and 4 in gastric adenocarcinoma. METHODS AND RESULTS: Eighty-nine cases of surgically resected human gastric adenocarcinoma were studied by immunohistochemistry. Of these, 60 (67.4%), 61 (68.5%), 69 (77.5%), 75 (84.3%), and 47 cases (52.8%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and 2 and Ang-1, 2 and 4 proteins, respectively. The expression of Ties and Angs was significantly correlated with several type of histological differentiation and several clinicopathological factors. CONCLUSIONS: Ties and Angs were highly expressed in human gastric adenocarcinoma cells. These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2003

Plasma adiponectin levels in women with anorexia nervosa.

Adiponectin is a plasma protein exclusively secreted by adipose tissue, which plays a role in modulating lipid and glucose metabolism. The plasma adiponectin concentration shows an inverse correlation with the body mass index in normal and obese individuals, but it has not been investigated in subjects with an extremely low body weight and undernutrition such as anorexia nervosa patients. We investigated plasma adiponectin levels in 21 females with anorexia nervosa. Nineteen healthy females served as the lean control group. The subjects with anorexia nervosa had a significantly lower weight and showed a tendency towards higher adiponectin levels than the control group. No correlation between adiponectin and BMI was found in patients with anorexia nervosa, while a linear negative correlation was seen in lean controls. The patient who showed the lowest adiponectin level reached a life-threatening state and required intravenous feeding in hospital. In association with improved nutrition and weight gain, the adiponectin level increased gradually until the body mass index was about 16 and then decreased subsequently as would be expected in lean normal subjects. These observations suggest that adipose tissue secretes less adiponectin and the adiponectin levels do not show an inverse correlation simply with body mass index in some subjects with severe undernutrition.

Adiponectin↗
PubMed2001

Role of a highly conserved YPITP motif in 2-oxoacid:ferredoxin oxidoreductase: heterologous expression of the gene from Sulfolobus sp.strain 7, and characterization of the recombinant and variant enzymes.

2-Oxoacid:ferredoxin oxidoreductase from Sulfolobus sp. strain 7, an aerobic and thermoacidophilic crenoarchaeon, catalyses the coenzyme A-dependent oxidative decarboxylation of pyruvate and 2-oxoglutarate, a cognate Zn-7Fe-ferredoxin serving as an electron acceptor. It comprises two subunits, a (632 amino acids) and b (305 amino acids). To further elucidate its structure and function, we constructed a gene expression system. The wild-type recombinant enzyme was indistinguishable from the natural one in every criterion investigated. A series of variants was constructed to elucidate the role of the YPITP-motif (residues 253-257) in subunit a, which is conserved universally in the 2-oxoacid:ferredoxin oxidoreductase (OFOR) family. Single amino-acid replacements at Y253 and P257 by other amino acids caused a drastic loss of enzyme activity. T256, the hydroxyl group of which has been proposed to be essential for binding of the 2-oxo group of the substrate in the Desulfovibrio africanus enzyme, was unexpectedly replaceable with Ala, the kcat and Km for 2-oxoglutarate being approximately 33% and approximately 51%, respectively, as compared with that of the wild-type enzyme. Replacement at other positions resulted in a significant decrease in the kcat of the reaction while the Km for 2-oxoacid was only slightly affected. Thus, the YPITP-motif is essential for the turnover of the reaction rather than the affinity toward 2-oxoacid.

Amino Acid Motifs↗
PubMed2001

Expression of tyrosine kinase receptors Tie-1 and Tie-2 in giant cell tumor of the tendon sheath: a possible role in synovial proliferation.

We have recently demonstrated that Tie-1 and Tie-2 are expressed in synovial cells from rheumatoid arthritis (RA). To elucidate the possible involvement of Tie receptors in synovial proliferation, we analyzed their expression by immunostaining in five cases of giant cell tumor of tendon sheath (GCTTS), which represents a proliferating lesion of synovial cells. Strong immunoreactivity for both Tie-1 and Tie-2, regardless of the individual patient's profile, was observed in all cases of GCTTS. Six sets of double immunohistochemical stainings for Tie-1/Tie-2 and fibronectin, CD68, or CD34 were carried out to determine the phenotype of Tie-1 and Tie-2-positive tumor components. In these studies, both Tie-1 and Tie-2 immunoreactivity were widely observed in the fibronectin-positive fibroblastic and the CD68-positive histiocytic mononuclear cells, as well as in the osteoclast-like giant cells. In tumor vasculature, Tie receptors were expressed in the CD34-positive endothelial cells possessing proliferating cell nuclear antigen (PCNA) immunoreactivity. We also evaluated the correlation of Tie-1/Tie-2 expression and proliferating cells in GCTTS by using double staining of Tie-1/Tie-2 together with PCNA. Overexpression of PCNA immunoreactivity was frequently found in Tie receptors-positive cells with no obvious differences in the expression pattern of Tie-1 and Tie-2. These findings suggest the possible involvement of Tie receptors in the pathogenesis of GCTTS other than solely via their involvement in angiogenesis and subsequent vascularization. It was demonstrated that Tie-2 immunoreactivity was restricted to the fibroblastic, but not histiocytic, phenotype in RA synovium, suggesting different regulatory control of Tie-2 expression in GCTTS and RA synovium. Overexpression of Tie receptors in GCTTS may imply a biological role for these receptors in synovial proliferation.

Adult↗
PubMed2001

Effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease.

The aim of this study was to explore the effects of nifedipine retard on heart rate and autonomic balance in patients with ischemic heart disease. Fourteen patients with ischemic heart disease (12 men and two women; mean age 64 years) were administered nifedipine retard at a daily dose of 20-40 mg. Changes in heart rate and autonomic balance were studied using Holter monitoring before and after 12 weeks of nifedipine therapy Heart rate was unchanged during sleep but was higher during the day after nifedipine retard administration. The high frequency power spectrum of heart rate variability (indicating parasympathetic activity) was lower during the day after nifedipine retard therapy but was unchanged during sleep. The low frequency power to high frequency power ratio, indicating sympathetic activity was unchanged during the day and during sleep. Nifedipine retard increased the heart rate of patients with ischemic heart disease only during the day and reduced parasympathetic activity.

Aged↗
PubMed2000

Expression of ICAM-1 and acute inflammatory cell infiltration in the early phase of radiation colitis in rats.

Inflammatory cell infiltration of the colon is observed at an early stage of radiation-induced colitis. The emigration of inflammatory cells from the circulation requires interactions between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. To elucidate this process, the present work analyzes the kinetics of the expression of intercellular adhesion molecule-1 (ICAM-1) and the accumulation of inflammatory myeloperoxidase (MPO)-positive cells in relation to the appearance of acute radiation colitis prior to an overt radiation-induced ulcer. Colon tissues were obtained from Wistar Kyoto rats at various times after 22.5 Gy irradiation to the rectum. Histologically, crypt depletion and numerous inflammatory cells were observed 4 days after irradiation, and mucosal ulcer 6 days after irradiation. ICAM-1 immunopositivity was present in the endothelial cells of small vessels in the mucosa of both control and irradiated rats. ICAM-1 mRNA expression was detected in normal colon and irradiated colon by reverse transcription-PCR. In Northern blotting, ICAM-1 mRNA levels were found to increase markedly in the irradiated colon compared to the normal colon. In Western blotting. ICAM-1 protein expression also increased with a peak one day after irradiation, and remained elevated up to 6 days thereafter. The number of MPO-positive cells in lamina propria mucosa increased in a time-dependent fashion from 6 h to 6 days after irradiation. These data suggest that up-regulation of ICAM-1 in endothelial cells and accumulation of MPO positive cells play important roles in the development of radiation-induced colonic ulcer.

Animals↗
PubMed1994

Analysis of AP-1 function in cellular transformation pathways.

To understand the role of endogenous AP-1 activity in cellular transformation induced by oncogenes, we have made use of a fos mutant (supfos-1) and a jun mutant (supjun-1), either of which can function as a transdominant inhibitor of AP-1-mediated transcriptional regulation. Chicken embryo fibroblasts (CEF) infected with a series of transforming retroviruses were doubly infected with retrovirus carrying supfos-1 or supjun-1, and suppression of cellular transformation was monitored in terms of reversion to normal cellular morphology or acquisition of anchorage-dependent growth. Cellular transformation induced by several exogenously expressed transforming genes of the fos or jun family was efficiently suppressed, as expected. CEF transformed by v-src, v-yes, v-fps, c-Ha-ras, and N-terminally truncated c-raf were also induced to revert to the normal phenotype by these transdominant mutants, suggesting that functional transcription factor AP-1 activity is essential for the cellular transformation induced by these oncogenes. The suppression is not attributable to nonspecific inhibition of cellular proliferation, because CEF transformed by v-ros or v-myc were not induced to revert to the normal phenotype. We next analyzed changes in all known components of chicken AP-1 induced by v-src, c-Ha-ras, or activated c-raf transformation. The levels of both Fra-2 and c-Jun expression were elevated two- to fourfold, and hyperphosphorylation of Fra-2 was also observed. We further showed that Fra-2-c-Jun heterodimer is mainly responsible for the elevated AP-1 DNA-binding activity in these transformed cells, and we propose that this heterodimer play a crucial role in the transformation induced by these oncogenes.

Animals↗
PubMed1988

[Study on the effectiveness and safety of cefmenoxime in the treatment of respiratory tract infections. Tendency toward clinical hemorrhage related to the treatment].

The effectiveness and safety of cefmenoxime (CMX) in the treatment of respiratory tract infections were evaluated, mainly in relation to the appearance of hemorrhagic tendency. Out of 80 patients treated in this study, 57 were treated with CMX alone, and an effective rate was determined to be 75.4%. As for a tendency toward hemorrhage, none of the patients clinically exhibited a hemorrhagic tendency, while the prolongation of prothrombin time (PT) and/or activated partial thromboplastin time (APTT) was seen in 3 patients (3.8%), who were all at ages over 63. The prolongation of APTT was clearly related to CMX in 1 patient. Although the causal relation between CMX and the prolongation of PT or APTT was unclear in the remaining 2 patients because they had severe primary diseases (lung cancer and respiratory failure due to chronic obstructive lung disease in addition to severe hepatic disorder and received combination treatment with anticancer agents or other antibiotics), CMX might have a role in causing these phenomena. Even though none of the patients showed a hemorrhagic tendency clinically arousing problems, we should be careful in using CMX in the treatment of the aged and patients in poor general conditions because PT and/or APTT was observed to prolong with the use of CMX in some patients.

Adolescent↗
PubMed1986

[Chemoembolization therapy with cisplatin.lipiodol (CDDP.lipiodol) in primary liver cancer--with special reference to hepatocellular carcinoma].

From Jan., 1985 to Mar., 1986 thirty-six patients with primary liver cancer received transcatheter arterial chemoembolization therapy with Cisplatin (100 mg) blended into Lipiodol (5 ml) and simple embolization therapy with Gelfoam particles. Thirty-three cases out of 36 had hepatocellular carcinoma, one had hepatoblastoma and one had adenocarcinoma. Ten (31%) out of 32 had hepatocellular carcinoma, and showed objective tumor reduction greater than 50% (partial response) regarding the main tumor. Of the 33 there was one sudden death due to intracerebral hemorrhage. Only two out of 25 cases with daughter nodules showed slight reduction. Almost all cases with daughter nodules showed no response to chemoembolization therapy. Five patients died after chemoembolization therapy during the fifteen-month study period. Two patients died of liver abscess or cholecystitis and surrounding abscess, one died of intracerebral hemorrhage, one died of hepatic failure and the remaining case was one of tumor death.

Carcinoma, Hepatocellular↗
PubMed1981

Age-dependent modifications of lipogenic enzymes.

When 1-, 2- and 9-month-old rats previously adapted to a commercial stock diet were fed a fat-free diet (induction) and also when the process was reversed (repression), the turnovers of lipogenic enzymes in liver were measured by following time courses for the change of the enzyme activities. The magnitudes of the induction of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were very high in 1-month-old rats and then decreased with aging. In the induction phase, the rates of synthesis of the enzymes were markedly decreased with increasing age as compared with the rate constants of degradation. The age-dependent alterations were not shown so much in the repression phase as in the induction phase. It is suggested that the age-dependent impairment in induction may be due to some alterations in the enzyme-forming system.

Acetyl-CoA Carboxylase↗
PubMed1980

Identification of shellfish fatty acids and their effects on lipogenic enzymes.

The fatty acids which are common to and characteristic of shellfish, were identified by mass spectrometry and NMR spectral analyses as being: octadecatetraenoioc acid, eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid. When the fatty acids isolated by high performance liquid chromatography were separately intubated into rats, hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49), malic enzyme (EC 1.1.1.40) and acetyl-CoA carboxylase (EC 6.4.1.2) were reduced more effectively as compared with linoleic acid intubation. These enzymes were reduced most markedly by eicosapentaenoic acid-intubation. The fatty acids seem to be effective components in reduction of triacylglycerol and lipogenic enzyme levels in rats fed on shellfish.

Acetyl-CoA Carboxylase↗
PubMed1980

Effect of oxidized oil on lipogenic enzymes.

Male Wistar rats were fed for 4 wk on diets containing 2% oxidized corn oil. Liver tissue was then studied to determine the effect of feeding peroxidized oil on lipogenic enzymes. Although substances which reacted with thiobarbituric acid increased in liver microsomes and mitochondria with increasing peroxide values of the dietary corn oil fed, the activities of glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase in liver were unchanged. However, when rats were fed for 2 wk on diets containing 10% fat, of which 0.5, 5 or 10% was unoxidized corn oil and the remainder was hydrogenated beef tallow filler, the lipogenic enzyme activities and also the liver triglyceride levels were observed to decrease with increasing amounts of dietary corn oil. Therefore, although a synthetic diet containing corn oil was easy to oxidize spontaneously, the reductions of lipogenic enzymes in rats fed the diet would not have been caused by lipid peroxides but by unsaturated fatty acids themselves.

Acetyl-CoA Carboxylase↗
PubMed1980

Effect of corn oil feeding on lipid peroxidation in rats.

Three groups of male rats were maintained on 10% fat diets containing 0.5, 5 or 10% corn oil or olive oil with 80--400 mg DL-alpha-tocopherol per kilogram. After 4 weeks on such regimens, TBA (thiobarbituric acid) values in serum, liver mitochondria and microsomes, and adipose tissue increased with rising amounts of dietary corn oil. TBA values in rats fed the 10% corn oil diet were reduced with the increase of dietary tocopherol but were still higher than the corresponding values of the 10% olive oil and 0.5% corn oil groups. When the liver microsomes were incubated with Fe3+-ADP and NADPH, the relative chemiluminescence emission in the visible region with the peroxidative cleavage of endogenous lipid was higher in the 5 and 10% corn oil groups than in the 0.5% group. On the other hand, when oxidized corn oil was given orally to rats with thoracic lymph fistula, TBA-reacting substances were recovered in thoracic lymph, but iodometric peroxide was undetectable. Therefore, TBA-reacting substances in rats fed the corn oil diets could have originated from the oxidative product of linoleic acid metabolism and also from the diet.

Adipose Tissue↗
PubMed1980

Effect of corn oil feeding on triglyceride synthesis in the rat.

When rats were fed diets containing 10% corn oil for 2 weeks, alpha-glycerophosphate acyltransferase and diacylglycerol acyltransferase levels were reduced to 75% of that of controls fed a 0.5% corn oil diet, while glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-Coa carboxylase levels were reduced to 28, 33 and 66%, respectively. The incorporation of labeled glycerol or palmitic acid into triglycerides by liver slices was also reduced by corn oil feeding. Therefore, it is suggested that although the major reduction of triglyceride synthesis by linoleic acid feeding is due to fatty acid synthesis, glycerolipid synthesis is also reduced.

Acetyl-CoA Carboxylase↗
PubMed1980

Reduction of lipogenic enzymes by shellfish triglycerides in rat liver.

When rats were fed for 2 weeks on 3% fat diets containing 0.5 or 1%corbicula (Corbicula japonica PRIME), clam (Tapes japonica) or oyster (Callocorchina) triglycerides, serum and liver triglyceride levels were significantly lowered. The activities of hepatic glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were markedly reduced in the rats. Cholesterol synthesis by liver slices was also reduced. The results of immunochemical titrations and Ouchterlony double-diffusion analysis indicated that the decreases in the activities of acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase were due to decreases in the enzyme quantities. The shellfish triglycerides include a high percentage of long chain and polyunsaturated fatty acids, which are common to and characteristic of the three kinds of shellfish. They would be effective components in these observations.

Acetyl-CoA Carboxylase↗
PubMed1980

A possible role of Z protein in dietary control of hepatic triacylglycerol synthesis.

The effects of fasting and refeeding on hepatic Z protein were investigated in rats. When [U-14C]palmityl-CoA was added to the liver cytosol fraction from fat-free refed rats, more binding of labeled palmityl-CoA to the Z-protein region was found than in the case of fasted rats. Also the radioactivities in specific precipitations of the palmityl-CoA binding protein with anti-Z immunoglobulin G were higher in the refed rats. The Z protein which stimulated diacylglycerol acyltransferase may be involved in the change of triacylglycerol synthesis in fasted and refed rat livers.

Acyltransferases↗