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Biomedical subjects

T Emoto

Publications and source records attributed to T Emoto.

At least 37 records · Page 2Linked to original sources
PubMed1991

Abnormal copper accumulation in non-cancerous and cancerous liver tissues of LEC rats developing hereditary hepatitis and spontaneous hepatoma.

We studied the copper concentrations in the non-cancerous and cancerous liver tissues of LEC rats with hereditary hepatitis and spontaneous hepatoma by atomic absorption spectrophotometry. Copper concentration in the non-cancerous livers of 29-month-old male LEC rats was comparable to that in the livers of LEC rats aged 2, 3 and 8 months whose hepatic copper concentrations were more than 40 times those of normal LEA rats. Copper concentration in spontaneously developed hepatocellular carcinomas of the 29-month-old male LEC rats was lower than that in the surrounding non-cancerous liver tissues, but was still more than 39 times that of 8-month-old male LEA rats. These findings suggest that in LEC rats an abnormal copper metabolism may be maintained during the process of hepatic carcinogenesis.

Age Factors↗
PubMed1991

Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease.

Long-Evans Cinnamon (LEC) rats, an inbred strain of a mutant rat isolated from Long-Evans rats, develop hereditary hepatitis. To elucidate the role of copper metabolism in the development of the hepatitis in LEC rats, we examined the copper concentration in the tissues and serum levels of copper and ceruloplasmin. Copper concentration in the liver of LEC rats was over 40 times that of normal Long-Evans Agouti (LEA) rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, resembling the histologic features of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity, and may be dealing with a rat form of Wilson's disease. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism and for developing treatment strategies for Wilson's disease and other abnormal copper metabolism in humans.

Animals↗
PubMed1990

Immunoreactive endothelin concentrations in maternal and fetal blood.

Immunoreactive-endothelin (ir-ET) concentrations were determined in peripheral maternal blood and in umbilical cord blood just after delivery. The concentrations in both the umbilical artery (2.83 +/- 1.36 pmol/l plasma, Mean +/- SD) and vein (3.37 +/- 1.53 pmol/l) were significantly higher than those found in maternal venous blood (1.43 +/- 1.02 pmol/l). On the other hand, ir-ET levels in maternal blood were not significantly different when compared with those found in non-pregnant women (1.50 +/- 0.83 pmol/l). No significant difference of ir-ET levels between the umbilical artery and vein was observed. A highly significant correlation (r = 0.60, p less than 0.01) of ir-ET levels between the umbilical artery and vein was observed. Also, a significant correlation (r = 0.48, p less than 0.01) between umbilical vein and maternal vein ir-ET levels with a weaker correlation (r = 0.36, p less than 0.05) between umbilical artery and maternal vein ir-ET levels was demonstrated. The present study indicates that ir-ET may be actively secreted in fetal circulation and the plasma levels in maternal and fetal circulation may have a possible relation.

Adult↗
PubMed1990

Inhibition by protein kinase-C inhibitor and cycloheximide of phorbol ester- and epidermal growth factor-induced arachidonic acid metabolism in cultured porcine thyroid cells.

In an attempt to elucidate possible mechanism(s) for stimulated arachidonic acid metabolism by phorbol 12-myristate 13-acetate (PMA) and epidermal growth factor (EGF) in porcine thyroid cells, we examined the effects of protein kinase inhibitors, isoquinolinesulfonamide derivatives (H-7 and HA-1004), and cycloheximide. The production of PGE2 stimulated by either PMA or EGF was strongly inhibited by H-7, with an ID50 value of approximately 20 to 25 mumol/L in each case, as well as by cycloheximide, with an ID50 value of less than 0.5 micrograms/mL in each case. In contrast, 100 mumol/L of HA-1004 showed less inhibition of PGE2 production provocated by either PMA or EGF. On the other hand, PGE2 production in basal or stimulated condition by exogenously added arachidonic acid, was inhibited to an even lesser extent by both H-7 and cycloheximide. The EGF- and PMA-stimulated release of 3H-arachidonic acid from the cells was also strongly inhibited by H-7 and cycloheximide. These results suggest an induction of synthesis of some proteins responsible for the release of arachidonic acid, which might be attributed to protein kinase-C activation in arachidonic acid metabolism stimulated by PMA or EGF. Moreover, PGE2 production was potently induced by PMA and slightly by EGF in the cyclooxygenase-inactivated cells by acetyl salicylate pretreatment, which also suggests that both agents might induce the synthesis of cyclooxygenase in cultured porcine thyroid cells, although we did not measure its activity.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Presence of high affinity receptor for interleukin-1 (IL-1) on cultured porcine thyroid cells.

Using 125I-interleukin-1 beta (125I-IL-1 beta) as a ligand, a specific receptor of high affinity dissociation constant (1.1 +/- 0.2 x 10(-10) M) with binding sites (350 +/- 40/cell) for interleukin-1 beta (IL-1 beta) has been demonstrated on cultured porcine thyroid cells. IL-1 alpha almost equally cross-reacted with the receptor (Kd = 1.2 +/- 0.3 x 10(-10) M and 350 +/- 50 binding sites/cell). TSH, IL-2 and other peptide hormones did not inhibit the binding of 125I-IL-1 beta to thyroid cells. Crosslinking study revealed a major band (approximately 95 kD) with a corrected molecular mass of approximately 78 kD. Moreover, both IL-1 beta and IL-1 alpha stimulated prostaglandin E2 production of cultured porcine thyroid cells, although the potency of IL-1 alpha was slightly greater than that of IL-1 beta. These results suggest that IL-1 may be involved in the regulation of thyroid cell function.

Animals↗
PubMed1990

[Hepatocellular carcinoma with extrahepatic malignancies].

A clinical investigation of 16 hepatocellular carcinoma (HCC) patients with extrahepatic malignancies (13 male, 3 female) has been conducted. The age of these patients ranged from 55 to 76 years. Three of these double cancer cases were hemocronous, and 13 were heterochronous. The duration between the occurrence of the cancers ranged from 2 years and 4 months to 22 years. As for the site of the other cancer, the stomach was the most common organ (12 cases). In nine cases out of 16, the HCC was resected, whereas the other cases were treated with a TAE and hepatic artery ligation because the cancer were far advanced stages. Early detection of an HCC by AFP or an ultrasonographic examination, and a subsequent surgical resection in cases of a postoperative cancer patient with a liver dysfunction may lead to a more favorable prognosis.

Aged↗
PubMed1990

[Tissue UFT distribution and histological changes following UFT administration in metastatic liver cancer cases].

For the purpose of assessing the anti-tumor effect of UFT in metastatic liver cancer, blood futraful (FT), 5-fluorouracil (5-FU) and uracil levels and their distribution in tissue (cancer lesion, etc.) following oral UFT administration were examined in 10 surgically treated cases of metastatic liver cancer secondary to cancer of the large intestine and 4 cases of metastatic liver cancer secondary to stomach cancer. Liver tissue 5-FU distribution following UFT treatment was excellent. 5-FU concentration in liver cancer lesion was 0.164 +/- 0.128 micrograms/g, which was markedly higher than the minimal effective tissue concentration for 5-FU (0.050 micrograms/g). 5-FU level in normal tissue of the organ with primary cancer was significantly lower than that in the tumor-affected tissue of the same organ, while no difference in 5-FU level was noted between cancer-affected and normal tissues of the liver. Tissue 5-FU level in both primary and metastatic cancer lesions was significantly higher than the simultaneously determined blood 5-FU level. Histological findings of cancer-affected liver did not differ between different UFT dose levels, but degeneration of cancer cells was severe in some cases given high doses of UFT.

Aged↗
PubMed1989

Regulation of thyroid peroxidase activity by thyrotropin, epidermal growth factor and phorbol ester in porcine thyroid follicles cultured in suspension.

The activity of thyroid peroxidase (TPO) in porcine follicles cultured for 96 h in suspension with five hormones (5H) still attained over 50% of that in the freshly isolated follicles. On the other hand, the activity in those cultured with 5H + TSH (6H) was several times higher than that cultured with 5H after 96 h, although an initial decrease of TPO activity during the first 24 h of culture was observed in both conditions. The ability of follicles to metabolize iodide (uptake and organification) when cultured with 6H for 96 h was also several times higher than that of those cultured with 5H. The half-maximal dose of TSH for stimulation of TPO activity and iodide metabolism was 0.03-0.04 mU/ml and the effect was mediated by cAMP. These results indicate that in porcine thyroid follicles in primary suspension culture, TPO activity as well as the ability of iodide metabolism is induced by chronic TSH stimulation. In addition, epidermal growth factor (EGF, 10(-9)M) and phorbol 12-myristate 13-acetate (PMA, 10(-8) M) completely inhibited TSH stimulation on both activities and also basal (5H) activity of iodide metabolism.

Animals↗
PubMed1988

Phorbol esters modulate cyclic AMP accumulation in porcine thyroid cells.

In cultured porcine thyroid cells, during 60 min incubation phorbol 12-myristate 13-acetate (PMA) had no effect on basal cyclic AMP accumulation and slightly stimulated cyclic AMP accumulation evoked by thyroid stimulating hormone (TSH) or forskolin. Cholera toxin-induced cyclic AMP accumulation was significantly stimulated by PMA. On the other hand, cyclic AMP accumulation evoked by prostaglandin E1 or E2 (PGE1 or PGE2) was markedly depressed by simultaneous addition of PMA. These opposing effects of PMA on cyclic AMP accumulation evoked by PGE and cholera toxin were observed in a dose-related fashion, with half-maximal effect of around 10(-9) M in either case. The almost same effects of PMA on cyclic AMP accumulation in basal and stimulated conditions were also observed in freshly prepared thyroid cells. The present study was performed in the presence of phosphodiesterase inhibitor, 3-iso-butyl-1-methylxanthine (IBMX), indicating that PMA affected adenylate cyclase activity. Therefore, it is suggested that PMA may modulate the production of cyclic AMP in response to different stimuli, possibly by affecting several sites in the adenylate cyclase complex in thyroid cells.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Characterization of adenovirus type 40 E1 region.

The left-most 3.9 kb of adenovirus type 40 (Ad40) DNA has been sequenced using cloned viral DNA fragments. The Ad40 E1 region is deduced to code for at least four polypeptides, 221 and 249 amino acids as E1A products in addition to 166 and 475 amino acids as E1B products. E1B polypeptides share about 50% homology with well-defined adenovirus types, 2/5, 7, and 12, throughout the E1B sequences. E1A homology of Ad40 to these types is relatively lower than that of E1B, while highly conserved regions of E1A are retained to a certain level in Ad40 as well. Activity for morphological transformation of Ad40 E1A on 3Y1 cells is considerably lower when compared to that of Ad5 and Ad12 E1A genes. Transient chloramphenicol acetyltransferase (CAT) expression assay shows that Ad40 E1A has a trans-acting function, though lower than that of other E1A genes, on adenovirus early promoter. The Ad40 E1A promoter also holds only a little cis-acting activity in 3Y1 cells. Lower activities of both Ad40 E1A promoter and certain E1A functions may explain in part the difficulty in propagation of Ad40.

Adenoviridae↗
PubMed1987

Stimulation of prostaglandin E2 production by phorbol esters and epidermal growth factor in porcine thyroid cells.

Effects of phorbol esters and epidermal growth factor (EGF) on prostaglandin E2 production by cultured porcine thyroid cells were examined. Both phorbol 12-myristate 13-acetate (PMA) and EGF stimulated prostaglandin E2 production by the cells in dose related fashion. PMA stimulated prostaglandin E2 production over fifty-fold with the dose of 10(-7) M compared with control. EGF (10(-7) M) also stimulated it about ten-fold. The ED50 values of PMA and EGF were respectively around 1 X 10(-9) M and 5 X 10(-10) M. Thyroid stimulating hormone (TSH), however, did not stimulate prostaglandin E2 production from 1 to 24-h incubation. The release of radioactivity from [3H]-arachidonic acid prelabeled cells was also stimulated by PMA and EGF, but not by TSH. These results indicate that both PMA and EGF are potent stimulators of prostaglandin E2 production, associated with the activity to stimulate arachidonic acid release in porcine thyroid cells.

Animals↗
PubMed1987

Presence of epidermal growth factor receptors on human thyroid membranes.

The nature of epidermal growth factor (EGF) receptors in normal and pathological thyroid membranes was studied on a crude membrane fraction (10,000 X g pellet) of tissue homogenate. Optimal binding of 125I-EGF to human thyroid membranes was obtained at 25 degrees C with 1-h incubation at pH 7.4. The study revealed the presence of both high and low affinity receptors in normal and pathological thyroid membranes. The association constants of high affinity receptor (3.2 X 10(-9) mol/l) and of low affinity receptor (1.8 X 10(-8) mol/l) observed in normal thyroid membranes were similar to those of thyroid membranes from neoplastic as well as thyrotoxic thyroid tissues. [3H]thymidine incorporation into DNA of cultured human thyroid cells was stimulated by EGF in a dose-dependent manner. A half-maximal stimulation was found around 1 X 10(-10) mol/l. These results suggest that EGF may have a possible role in the regulation of thyroid growth and function in physiological and pathological situations.

Animals↗
PubMed1986

Prostacyclin stimulation of adenylate cyclase activity in human thyroid membranes.

Effect of prostacyclin (PGI2) on adenylate cyclase activity in human thyroid membranes was examined. PGI2 caused a dose- and time-dependent production of cyclic AMP (cAMP) with high potency. When GTP was added in concentrations up to 100 uM, the activation of adenylate cyclase by PGI2 was increased. In the assay medium containing 3 mM ATP, 10 uM GTP and nucleotide regenerating system, the replacement of Mg2+ by increasing concentrations of Mn2+ caused a progressive loss of PGI2 as well as TSH-stimulated adenylate cyclase activities, while high concentrations of Mg2+ (12 or 18 mM) slightly suppressed the activity stimulated by either PGI2 or TSH. Both agents had an additive effect on the stimulation of adenylate cyclase activity in the presence of either 6 mM Mg2+ or 6 mM Mn2+. Gamma-globulin fraction containing non-stimulatory TSH receptor antibody which was prepared from a patient with chronic thyroiditis, suppressed only TSH- but not PGI2-stimulation of the adenylate cyclase activity. These results suggest that PGI2 can stimulate the adenylate cyclase activity in human thyroid tissue, and that PGI2-stimulation may be mediated by the different system from TSH-dependent one.

Adenylyl Cyclases↗
PubMed1985

Forskolin stimulation of adenylate cyclase in human thyroid membranes.

Forskolin stimulates adenylate cyclase in human thyroid membranes approximately 7-fold with half-maximal stimulation occurring at 5-10 microM. Guanine nucleotides are not required for stimulation of the enzyme by forskolin. Forskolin-stimulation is additive or greater than additive with that of TSH or Gpp(NH)p- (above 1 microM). Different from TSH- or Gpp(NH)p-stimulation of adenylate cyclase, uncoupling of the guanine nucleotide-binding regulatory component by increasing concentrations of MnCl2 did not result in uncoupling of forskolin stimulation. The finding indicates that forskolin may mainly act on the catalytic component of adenylate cyclase. From the present study, it is suggested that the diterpene forskolin stimulates adenylate cyclase in human thyroid membranes by a novel mechanism that differs from TSH- or Gpp(NH)p-stimulation, and that the diterpene may be a useful tool to investigate the metabolism of thyroid and its regulation in normal and pathological situations.

Adenylyl Cyclases↗