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Biomedical subjects

Y Hitomi

Publications and source records attributed to Y Hitomi.

At least 19 recordsLinked to original sources

Laminin-rich extracellular matrix maintains high level of hepatocyte nuclear factor 4 in rat hepatocyte culture.

Laminin-rich extracellular matrix, EHS-gel, has been demonstrated to keep a high level of liver-specific gene expression in cultured rat hepatocytes. To obtain information about the effect of EHS-gel on liver-specific functions, gene expression of liver-enriched transcription factors in rat hepatocytes was investigated. The apolipoprotein A-I and albumin mRNA levels were higher in hepatocytes cultured on EHS-gel than in those cultured on type I collagen (TIC). The levels of mRNA for HNF-4, C/EBP alpha and C/EBP beta were also higher on EHS-gel than on TIC. The level of HNF-4 mRNA in hepatocytes on EHS-gel was almost comparable to that in liver. The HNF-3 alpha mRNA level was lower on EHS-gel than on TIC. C/EBP beta mRNA was induced by dexamethasone in both EHS-gel and TIC. The induction of C/EBP alpha and HNF-4 by dexamethasone was observed only on TIC. These data suggest that EHS-gel leads hepatocytes to keep the phenotypic expression through high expression of liver-enriched transcription factors, such as HNF-4.

Animals

Differential expression of the T cell receptor/CD3 genes and their lymphoid-specific transcription factor genes in murine T cell x fibroblast and T cell x B cell hybrids.

We generated cell hybrids between mouse T cell lymphoma EL4 cells and mouse fibroblast B82 cells (BELIII and BELIV) to examine the expression of T cell receptor (TcR)/CD3 genes and their lymphoid-specific transcription factor genes, which are normally detected in EL4 cells. In BELIII and BELIV, expression of the TcR alpha, TcR beta and CD3 delta genes was extinguished, whereas expression of the CD3 epsilon gene was still detected. Expression of the (lymphoid enhancer binding factor 1) LEF-1 gene was extinguished and that of the GATA-3 gene was hardly detected in BELIII and BELIV. Ets-1 gene expression, observed not only in EL4 cells but also in B82 cells, was considerably reduced in BELIII and BELIV. A much higher level of PEBP2 alpha A gene expression was observed in B82 cells than in EL4 cells and was preserved in BELIII and BELIV. To examine whether reduced expression of these genes is also found in T cell x B cell hybrids, we generated an additional cell hybrid between EL4 cells and mouse plasmacytoma S194 cells (SELIII). Marked differences were observed in the expression of the TcR alpha, CD3 delta, LEF-1 and PEBP2 alpha A genes in BEL and SEL hybrids. Expression of the TcR alpha, CD3 delta and LEF-1 genes, which was extinguished in BELIII and BELIV, was detected in SELIII. PEBP2 alpha A gene expression, not detected in S194 cells, was considerably reduced in SELIII. Almost the sum of the chromosomes from the parental cells were retained by, and the presence of every gene was proven, in each cell hybrid. These results suggest that suppression of the expression of lymphoid-specific transcription factor genes may precede that of the TcR/CD3 genes in the cell hybrids, and that the presence of a different trans-acting negative regulatory mechanism(s) suppresses the expression of T cell specific genes in fibroblasts and B cells.

Animals

The effect of phlebotomy on serum erythropoietin levels in normal healthy subjects.

We evaluated endogenous serum erythropoietin (Epo) levels in 14 normal subjects (eight males and six females) after a single 400-ml phlebotomy. The subjects were followed up for 56 days. The hemoglobin (Hb) values of both males and females decreased to a nadir on days 3 to 7 post-phlebotomy. Hb values gradually increased, but did not completely recover to pre-phlebotomy levels by day 56. Serum Epo levels increased after 6 h post-phlebotomy, to 20.1 +/- 5.4 (mU/ml) in males and 20.7 +/- 7.0 in females, from the pre-phlebotomy levels of 14.6 +/- 4.0 in males and 13.4 +/- 4.1 in females, respectively. Epo levels continued to increase to peak levels of 25.5 +/- 6.3 in males and 28.7 +/- 11.5 in females on days 7 to 14 and thereafter decreased until day 56. Thus, the Epo response to a 400-ml phlebotomy was relatively small in magnitude and was not sufficient to initiate a significant increase in erythropoiesis. This finding suggests that the administration of recombinant human erythropoietin (rHu-Epo) may be effective for the prompt correction of anemia induced by autologous blood donation and for increasing the volume of predonated autologous blood.

Adult

Alteration of serum lipoprotein metabolism by polychlorinated biphenyls and methionine in rats fed a soybean protein diet.

The effects of dietary supplementation of methionine to a 20% soybean protein isolate diet on serum lipoprotein profiles and secretion rate of VLDL in rats receiving polychlorinated biphenyls (PCB) were investigated. Serum cholesterol levels were higher in rats fed PCB or a methionine supplement than in controls. The effects of PCB and methionine were synergistic. The feeding of PCB resulted in more cholesterol in all fractions of serum lipoproteins tested, especially HDL (HDL1 and HDL2). Dietary supplementation of methionine primarily increased HDL cholesterol. The elevation of serum lipoprotein cholesterol due to PCB and/or methionine was significant in HDL1, which showed alpha-mobility. These results showed that methionine and PCB significantly influenced HDL metabolism. The secretion rate of VLDL was higher in rats fed PCB than in controls, but the addition of methionine to diets did not affect the secretion rate of VLDL cholesterol. This implies that PCB increased serum cholesterol partly through the stimulation of VLDL cholesterol secretion.

Administration, Oral

Design, synthesis and antiinflammatory activity of a new indomethacin ester. 2-[N-[3-(3-(piperidinomethyl)phenoxy)propyl]carbamoylmethylthio]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate.

A novel indomethacin ester prodrug, 2-[N-[3-(3-(piperidinomethyl)phenoxy)propyl]carbamoylmethylthio ]ethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate (1) was prepared from a new histamine H2-receptor antagonist, N-[3-(3-(piperidinomethyl)phenoxy)propyl]-2-(2-hydroxyethylthio )acetamide (2) and indomethacin (3). The compound 1 was shown to be essentially similar to 3 in its antiinflammatory action and to almost completely inhibit carrageenin-induced hind-paw edema in the rat at a very high dose of 230 mg/kg (280 mumol/kg), which is comparable to that of 100 mg/kg (280 mumol/kg) of 3, without producing gastric lesions. On a molar basis, the acute gastric lesioning properties of 1 were near one-hundred times less than those of 3, resulting in over a twenty-fold improvement in the ratio of antiedema activity to ulcerogenicity. The effect of the co-administration of histamine H2-receptor antagonists on antiedema activity and ulcerogenicity caused by 3 is also discussed.

Animals

Elevated gelsolin and alpha-actin expression in a flat revertant R1 of Ha-ras oncogene-transformed NIH/3T3 cells.

Expressions of gelsolin and alpha-actin have been investigated in a revertant cell line R1 and compared with the parental human activated Ha-ras oncogene-transformed NIH/3T3 (EJ-NIH/3T3), untransformed NIH/3T3 and partially revertant R2 cells. Gelsolin mRNA expression was strongest in R1 cells, intermediate in R2 and NIH/3T3 cells, and low in EJ-NIH/3T3 cells. Southern blot analysis gave neither signs of gross rearrangements nor amplification of the gelsolin gene. alpha-actin mRNA expression was restored in R1 cells to the level of NIH/3T3 cells. In R2 and EJ-NIH/3T3 cell lines, no alpha-actin transcript was detected. High gelsolin expression and restoration of alpha-actin expression may be associated with the acquirement of flat morphology and ordered cell growth pattern, which imply loss of tumorigenicity of R1 cells.

Actins

Effect of dietary methionine and polychlorinated biphenyls on cholesterol metabolism in rats fed a diet containing soy protein isolate.

The effects of supplementation of methionine to a 20% soy protein isolate diet on serum level of cholesterol. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, cholesterol 7 alpha-hydroxylase activity, and biliary and fecal steroids in rats with or without receiving polychlorinated biphenyls (PCB) were investigated. Supplementation of methionine and PCB did not affect the growth. Serum level of cholesterol was higher in rats fed PCB than in controls. In rats fed PCB, addition of methionine elevated serum level of cholesterol synergistically. The activity of HMG-CoA reductase was higher in rats fed the methionine-supplemented diet than in those fed the unsupplemented diet when PCB was included in the diets. Cholesterol 7 alpha-hydroxylase activity (nmol/h.100 g body weight) was higher in rats fed PCB than in controls. Biliary secretion of bile acids was higher in rats fed PCB than in controls. On the other hand, fecal excretion of bile acids decreased in PCB-treated rats, but total steroids were not affected by PCB. In rats fed PCB, the addition of methionine did not alter cholesterol 7 alpha-hydroxylase activity and biliary and fecal steroid output. The data suggest that the increase in serum level of cholesterol due to dietary addition of methionine together with PCB would be mediated through the stimulation of hepatic synthesis of cholesterol.

Animals

Effect of methionine and threonine on the hypercholesterolemia induced by polychlorinated biphenyls in rats fed a nonprotein diet.

It was previously reported that the hypercholesterolemia induced by polychlorinated biphenyls (PCB) was influenced by dietary protein quantity and quality. On the other hand, the supplementation of methionine and threonine to a nonprotein diet ameliorated the body weight loss and decreased the urinary urea excretion in rats. We examined the effect of methionine and threonine supplements on the hypercholesterolemia induced by PCB in rats fed a nonprotein diet. The administration of PCB increased plasma cholesterol concentration and the supplements of methionine and threonine to the nonprotein diet significantly accelerated the elevation of plasma level of cholesterol due to PCB feeding. Liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in rats fed the nonprotein diet was also elevated by PCB administration and the supplementation of methionine and threonine caused further inducing effect.

Animals

New synthetic substrate for kallikrein and its application.

We developed a new synthetic substrate, Pro-Phe-Arg-alpha-naphthyl ester, for kallikrein. We found that this substrate had higher specificity and sensitivity for kallikrein and was applied for the preparation of zymogram and for the histochemical demonstration. With Pro-Phe-Arg-alpha-NE as substrate, the minimum detectable concentration of human urinary kallikrein was about 0.001 KU and then kallikrein could be determined with 25 microliter of human urine. We also found the possibility that occurring of abnormalities during pregnancy were predicted by the determination of urinary kallikrein of pregnants. Zymograms were prepared for various kinds of kallikrein using this substrate. The localization of kallikrein-like enzyme in rat kidneys was defined by the application this substrate for histochemistry. Moreover, cytochemical demonstrations of leucocytes in human blood were done using Ts-Lys-alpha-NE and Ac-Tyr-alpha-NE.

Animals

[Pseudoaneurysm of the left ventricle serially demonstrated from on-set using two-dimensional echocardiography: a case report].

A case of so-called pseudoaneurysm of the left ventricle without pericardial adhesion, serially demonstrated by two-dimensional echocardiography, was reported. A 76-year-old man developed congestive heart failure 10 hours after gastrectomy, and was diagnosed as having acute myocardial infarction. Two-dimensional echocardiography on the 21st day after onset revealed moderate pericardial effusion and an echo-free space in the posterolateral myocardium of the left ventricle. The echo-free space gradually expanded exteriorly and formed an aneurysm, which remained unchanged after the resolution of the pericardial effusion. Clinical diagnosis of pseudoaneurysm of the left ventricle was made by left ventriculography and coronary angiography. At autopsy, there was an aneurysm measuring 2.3 X 3.0 X 5.0 cm which communicated with the left ventricle via two small ostia, 5 mm each in diameter. There was a loose fibrous adhesion between the pericardium and the epicardium. The wall of the aneurysm consisted of organized fibrous tissue without any elements of the myocardium. Both myocardium and fibrous tissue were located at the junction of the left ventricular wall and the aneurysm. It is surmised that dissection of the infarcted myocardium expanded so greatly as to form an aneurysmal cavity, resulting in the formation of a so-called pseudoaneurysm of the left ventricle after fibrous changes of the outer wall in the infarcted myocardium. Therefore, this aneurysm might be termed a "dissecting" aneurysm of the left ventricle. The hypothesis that a pseudoaneurysm is derived from a localized hemopericardium should be reconsidered.

Aged

Inhibitory effect of a new synthetic protease inhibitor (FUT-175) on the coagulation system.

The inhibitory effects of 6-amidino-2-naphthyl-4-guanidinobenzoate X dimethanesulfonate (FUT-175) on the human Hageman factor fragment (HFf), factor Xa, thrombin, plasma kallikrein, and plasmin were studied. FUT-175 inhibited plasma kallikrein most (IC50 = 3.0 X 10(-9) M), followed by HFf (IC50 = 3.3 X 10(-7) M). FUT-175 was found to have an anticoagulant effect in the APTT and PT assay systems of human plasma. The concentration of FUT-175 for twofold increase in the clotting time in the APTT assay system was 5 X 10(-7) M.

Anticoagulants