PubMed Health⌕ Search

Biomedical subjects

M Isogai

Publications and source records attributed to M Isogai.

At least 37 records · Page 2Linked to original sources

[Targeted chemotherapy of hepatocellular carcinoma with SMANCS/Lipiodol--how to use SMANCS/Lipiodol].

The first drug only for arterial injection, SMANCS/Lipiodol, which offers targeted chemotherapy for hepatocellular carcinoma (HCC), now commercially available. Based on our experience using SMANCS/Lipiodol for 424 patients with HCC, the golden standard of how to use SMANCS/Lipiodol for complete necrosis of tumor was described. The initial dose of SMANCS/Lipiodol was varied 2 to 6 mg per body, mainly depending on the size of the tumor. All feeding arteries of HCC have to be verified on angiogram, and the drug must be injected via an adequate artery. Sometimes, a tumor changes its feeding arteries. Additional administrations with an interval of one month were done till the entire tumor was filled with SMANCS/Lipiodol (grade 4). One or two months after achievement of grade 4, we must examine how much drug was removed from tumor on CT. If the entire tumor is not filled with the drug, further injections are recommended to maintain grade 4. Almost all tumors shrank in 3 to 4 months while maintaining grade 4. Frequent administration of low doses (1-3 mg per body) is recommended. Discontinvation of administration was done on the following findings; tumor size reduction of over 90% or complete disappearance of tumor stain. With arterial injection therapy of SMANCS/Lipiodol, survival of patients with unresectable HCC was prolonged, especially in 272 patients who were good candidates for therapy. (Those with Child C liver cirrhosis, with a tumor occupying all four segments of the liver, and/or with extrahepatic spread at initial arterial injection of the drug were excluded.) The 1, 2, 5, and 10 year survival rates were 83%, 58%, 34%, and 25%, respectively.

Antineoplastic Agents↗

Expression of a dominant-negative retinoic acid receptor construct reduces retinoic acid metabolism and retinoic acid-induced inhibition of NIH-3T3 cell growth.

We have previously reported an unexpected relationship between retinoic acid-induced inhibition of cell growth and the ability of various cell lines to metabolize the retinoid. Here, we report that stable expression of the truncated retinoic acid receptor RAR alpha403, transduced in NIH-3T3 cells by a retroviral vector, rendered the cells resistant to retinoic acid for growth inhibition and reduced their ability to metabolize the retinoid at the same time as it blunted the induction of the target gene transglutaminase II. The data suggest that retinoic acid receptors mediate the growth-inhibitory action of retinoic acid as well as its metabolism and the induction of transglutaminase II.

3T3 Cells↗

Marmoset liver cytochrome P450s: study for expression and molecular cloning of their cDNAs.

Northern blot and immunoblot analyses indicated that considerable levels of CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A were expressed in the liver of untreated marmosets. CYP1A was also expressed but to lesser extents. CYP3A mRNA was also detectable in the small intestine of untreated marmoset; the amount was increased by treatment with polychlorinated biphenyl. From a liver cDNA library, two cDNA clones coding for CYP2D19 and CYP3A21 (clones CM2D-1 and CM3A-10, respectively) were isolated. CM2D-1 and CM3A-10 contained an entire coding region for polypeptide 497 and 503 amino acid residues, respectively. The deduced amino acid sequences of CYP2D19 and CYP3A21 showed 90% identities to human CYP2D6 and CYP3A4, respectively. The value of CYP3A21 was 3% lower than that of cynomolgus monkey CYP3A8. On the other hand, these values were 11 to 23% higher than those of the other experimental animals, including dogs, rabbits, guinea pigs, rats, mice, and hamsters. These results indicate that the marmoset stands at a midpoint between human and nonprimate experimental animals.

Amino Acid Sequence↗

Hepatic calcium-binding protein regucalcin concentration is decreased by streptozotocin-diabetic state and ethanol ingestion in rats.

The alteration in calcium-binding protein regucalcin in the liver and serum of rats with streptozotocin (STZ)-diabetic state or ethanol ingestion was investigated. STZ (6.0 mg/100 g body weight) was subcutaneously administered in rats, and 1 or 3 weeks later they were sacrificed by bleeding. Liver regucalcin mRNA levels were not clearly altered by the diabetic state, as evidenced by Northern blotting using regucalcin cDNA (0.9 kb of open reading frame). Based on enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG, hepatic regucalcin concentration was decreased about 50% of control levels by STZ treatment. However, serum regucalcin concentration was not significantly altered by STZ treatment. Meanwhile, when rats ingested ethanol (10 and 30%) in the drinking water for 2 weeks, liver regucalcin mRNA levels were clearly increased, although hepatic regucalcin concentration was significantly decreased. Serum regucalcin concentration was not appreciably altered. Serum transaminases (GOT and GPT) activities were significantly increased at 1 or 3 weeks after STZ administration in rats, while their activities were not altered by ethanol ingestion. The present study demonstrates that hepatic regucalcin concentration is decreased independent of mRNA expression in the STZ-diabetes and during ethanol ingestion in rats.

Animals↗

Potential sensitivity of hepatic specific protein regucalcin as a marker of chronic liver injury.

A novel calcium-binding protein regucalcin has been shown to be specifically expressed in the liver of various specifies including human. Regucalcin concentration in the serum of patients with chronic liver injury was estimated by enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG. Serum samples were obtained from 42 persons who were diagnosed as liver disorder. Serum regucalcin concentration in all patients was in the range of 3.7-69.6 ng/ml, although regucalcin was not entirely seen in the serum of normal subjects (10 persons) without hepatitis. Meanwhile, in 18 patients with liver injury, serum glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) activities were normal value (less than 40 I.U./I). Serum GOT and GPT activities from 24 patients showed a comparatively higher level (50-234 I.U./I). The present results demonstrate the potential sensitivity of regucalcin as a marker of chronic liver injury.

Alanine Transaminase↗

Marmoset CYP1A2: primary structure and constitutive expression in livers.

Complementary DNA of marmoset CYP1A2 was isolated by means of screening the cDNA library and reverse-transcriptase polymerase chain reaction. The deduced amino acid sequence of marmoset CYP1A2 consisted of 516 residues and showed 88.2 and 90.0% identities to corresponding forms in human and cynomolgus monkey, respectively. S1 nuclease protection assay demonstrated that CYP1A2 mRNA was expressed constitutively in the liver, but not in the lung, kidney and small intestine. The level of CYP1A2 mRNA in the liver was increased by treatment with 3-methylcholanthrene and polychlorinated biphenyls. Marmoset CYP1A2 expressed in recombinant yeast activated 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) efficiently, and also activated 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), but at a relatively lower rate in the umu mutagenicity test. Marmoset CYP1A2 also showed ethoxyresorufin O-de-ethylase activity. Based on these results, we demonstrate that marmosets constitutively express CYP1A2 in the liver as in humans.

Amino Acid Sequence↗

The loss of outer capsid protein P2 results in nontransmissibility by the insect vector of rice dwarf phytoreovirus.

A transmission-defective (TD) isolate of rice dwarf phytoreovirus lacked the ability to infect cells when derived from the virus-free insect vector Nephotettix cincticeps. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified virus showed that among six structural proteins, the P2 outer capsid protein (encoded by genome segment S2) was absent from the TD isolate, whereas all six proteins were present in the transmission-competent (TC) isolate. P2 was not detected on immunoblots of rice plants infected with the TD isolate. Genome segment S2 and its transcript were detected in both TD and TC isolates. Sequence analysis of the S2 segment of the TD isolate revealed the presence of a termination codon due to a point mutation in the open reading frame, which might explain the absence of P2 in the TD isolate. These results demonstrate that the P2 protein is one of the factors essential for infection by the virus of vector cells and, thus, influences transmissibility by vector insects.

Amino Acid Sequence↗

Details of the arrangement of the outer capsid of rice dwarf phytoreovirus, as visualized by two-dimensional crystallography.

Two-dimensional crystals were obtained from purified P8, an outer capsid protein of rice dwarf phytoreovirus. A filtered image of the two-dimensional crystal, in combination with the results of biochemical analysis, revealed the unit formation of the capsid protein, a capsomere structure, which appeared to be an approximately equilateral triangle with sides of approximately 6 nm and which was composed of a trimer of P8 protein. Details of the arrangements of the outer capsid of the virus are described.

Capsid↗

[Administration and dosage of fluorouracil (5-FU) continuous i.v. infusion in patients with non-curative resected/non-resected gastric cancer].

This study was conducted to establish the optimum postoperative adjuvant chemotherapy with 5-FU in patients with gastric cancer. Seventy gastric cancer patients were treated after surgery with one of the following regimens; 5-FU 10 mg/kg/24 hrs c.i.v. x 24 days (arm A, n = 25); 5-FU 20 mg/kg/24 hrs c.i.v. x 4 days/w x 3 courses (arm B, n = 16); 5-FU 30 mg/kg/24 hrs c.i.v. x 2 days/w x 4 courses (arm C, n = 25). Blood 5-FU concentration, adverse effects and prognosis in each arm were compared. Changes in blood 5-FU concentrations were dose-related. The three-year survival rates in arms A, B and C were 15.0, 13.5 and 0.0%, respectively; they tended to be greater in arms A and B, but differences were not statistically significant. The most frequent adverse effects of the treatments were gastrointestinal, such as stomatitis. The incidence of reactions tended to be low in arm C, i.e., high-dose intermittent administration. Arm B (4 days-on, 3 days-off) was modified to 4 days-on, 6 days-off (arm B'), because severe stomatitis developed. The severity and incidence of stomatitis were reduced in the modified arm B group. We believe that intensive postoperative adjuvant chemotherapy for patients with gastric cancer should be designed using the arm B' approach.

Adult↗

Fibromuscular dysplasia of the visceral arteries.

Fibromuscular dysplasia (FMD) commonly involves the renal and carotid arteries. However, visceral arterial involvement is rare. We report a 39-yr-old male who developed ischemic bowel disease twice (once in the jejunal artery and once in the sigmoid artery) as a result of FMD. First ischemic change occurred in the sigmoid colon with manifestation of melena and abdominal pain, and the second occurred in the jejunum, with severe abdominal pain and intestinal stenosis. Angiography revealed the "string of beads" appearance, characteristic of FMD, in those two arteries responsible for the ischemic lesions. Fasting therapy with intravenous hyperalimentation improved both lesions, but secondary stenosis caused by ischemia occurred in the jejunum. Surgical resection of the stenotic jejunum was required. Although the abnormal arteries that had been imaged as a "string of beads" on angiography were not resected, the postoperative course has been uneventful and satisfactory.

Abdominal Pain↗

[A case of internal supravesical hernia].

We report a case of internal supravesical hernia. A 74-year-old male with complaint of abdominal pain underwent an operation for small intestinal obstruction due to its incarceration into the internal supravesical hernia. Retrospectively, the preoperative abdominal CT film showed the relation of the incarcerated intestine, the urinary bladder, and the middle umbilical ligament. This is the first case of the internal supravesical hernia in which the preoperative CT had taken and it will contribute to the preoperative correct diagnosis in the future.

Aged↗

Characterization of hepatic microsomal cytochrome P-450 from rats treated with methylsulphonyl metabolites of polychlorinated biphenyl congeners.

The inducing potency of 3-methylsulphonyl(MeSO2)-2,2',4',5,5'-pentachlorobiphenyl (pentaCB), which was one of the major MeSO2 metabolites of polychlorinated biphenyls (PCBs) present in seal blubber, on the hepatic drug metabolizing enzyme activities was examined in comparison with that of the parent compound and phenobarbital (PB). The inducing fashion of the above enzymes and changes in the contents of PB-inducible P-450 forms by 2,3',4',5-tetrachlorobiphenyl (tetraCB) (IU-70), 2,2',3',4',5-pentaCB (IU-87), 2,2',4',5,5'-pentaCB (IU-101) and 2,2',3',4',5,5'-hexachlorobiphenyl (hexaCB) (IU-141), and their MeSO2 metabolites were investigated in rats. Administration at various doses (0.2-1.0 mumol/kg) of 3-MeSO2-2,2',4',5,5'-pentaCB produced nearly dose-related increases in the hepatic concentration of this methyl sulphone, in the contents of cytochromes P-450 and b5, and in activities of aminopyrine N-demethylase, 7-ethoxycoumarin O-deethylase and benzo[a]pyrene hydroxylase of liver microsomes. Major PB-inducible forms, CYP2B1, CYP2B2, CYP3A2 and CYP2C6 were induced with four PCBs (342 mumol/kg) and their 3-MeSO2 metabolites (0.5-10 mumol/kg), indicating that 3-MeSO2 metabolites were strong PB-type inducers of hepatic drug-metabolizing enzymes. 3-MeSO2-2,2',4',5,5'-pentaCB was an especially strong inducer. On the other hand, four PB-inducible forms of cytochrome P-450 were not induced with the 4-MeSO2 isomers. The relation between liver concentrations of the corresponding 3-MeSO2 derivatives and induction of four PB-inducible forms of cytochrome P-450 after administration of four PCBs and their 3-MeSO2 derivatives further confirmed that the 3-MeSO2 metabolites played an important role in the induction which parent PCB congeners caused on the hepatic drug-metabolizing enzyme system.

Animals↗

Calcium administration increases calcium-binding protein regucalcin concentration in the liver of rats.

The alteration of regucalcin concentrations in the liver and serum of rats administered orally calcium is investigated. Rats received a single oral administration of calcium chloride solution (25, 50 and 75 mg Ca/100 g body weight). The administration of calcium (50 mg/100 g) produced a significant increase in liver regucalcin concentration between 30 and 180 min after the administration, while serum regucalcin concentration was not altered appreciably. The effect of calcium administration increasing liver regucalcin concentration was also seen with the dose of 25 mg/100 g. When liver cytosol prepared from normal rats was incubated for 6 h in the presence of 10 microM Ca2+, the cytosolic regucalcin concentration at 3 and 6 h of incubation was decreased about 20% (p < 0.05) as compared with the value at zero time point, indicating that the presence of Ca2+ does not inhibit the decomposition of liver cytosolic regucalcin. Moreover, serum regucalcin concentration was not significantly altered by the incubation for 6 h at 37 degrees C, indicating a stability of regucalcin in rat serum. This suggests that the calcium administration-induced in liver regucalcin concentration is not based on the inhibition of regucalcin release from liver to serum. The present study demonstrates that regucalcin in the liver is clearly increased by calcium administration, presumably due to stimulating the protein synthesis.

Animals↗

Specific species and tissue differences for the gene expression of calcium-binding protein regucalcin.

The existence and expression of gene encoding the Ca(2+)-binding protein regucalcin in various species and tissues were investigated with Southern and Northern hybridization analyses using regucalcin cDNA (0.9 kb of open reading frame). Genomic Southern hybridization analysis demonstrated that regucalcin gene was widely conserved among higher animals including human, monkey, rat, mouse, dog, bovine, rabbit and chicken. The gene was not found in yeast. The Northern blot analysis of poly (A) +RNAs extracted from the liver of various species showed that regucalcin mRNA was predominantly expressed in rat and mouse, although the expression was also seen in human, bovine and chicken. Furthermore, the enzyme-linked immunoadsorbent assay (ELISA) with rabbit-anti-regucalcin IgG indicated that hepatic regucalcin concentration was most pronounced in rat as compared with that of guinea pig, mouse and chicken. These observations show that the gene expression of regucalcin and its protein synthesis is unique in the liver of rats, suggesting the existence of a specific mechanism in demonstrating regucalcin synthesis from gene.

Animals↗

Expression of hepatic calcium-binding protein regucalcin mRNA is elevated by refeeding of fasted rats: involvement of glucose, insulin and calcium as stimulating factors.

The effect of refeeding on the expression of Ca(2+)-binding protein regucalcin mRNA in the liver of fasted rats was investigated. When rats were fasted overnight, the hepatic regucalcin mRNA level was reduced about 70% of that in feeding rats. Refeeding produced a remarkable elevation of hepatic regucalcin mRNA level (about 150-170% of fasted rats). Liver regucalcin concentration was appreciably increased by refeeding, although it was not altered by fasting. The oral administration of glucose (2 g/kg body weight) to fasted rats caused a significant increase in hepatic regucalcin mRNA level. Moreover, hepatic regucalcin mRNA level was clearly elevated by a single subcutaneous administration of insulin (10 and 100 U/kg) to fasted rats. The hormonal effect was not further enhanced by the simultaneous administration of calcium chloride (250 mg Ca/kg) to fasted rats, although calcium administration stimulated regucalcin mRNA expression in the liver. The present study suggests that the expression of hepatic regucalcin mRNA stimulated by refeeding is significantly involved in the action of insulin and/or calcium as stimulating factors.

Animals↗