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Biomedical subjects

M Furutani

Publications and source records attributed to M Furutani.

At least 73 records · Page 4Linked to original sources
PubMed1994

Identification of the thromboxane A2 receptor in hepatic sinusoidal endothelial cells and its role in endotoxin-induced liver injury in rats.

The presence of the thromboxane A2 receptor in sinusoidal endothelial cells was investigated and its pathogenic role in endotoxin-induced liver injury examined. The receptor was measured with a binding assay using a specific thromboxane A2 receptor antagonist, [3H]S-145. Scatchard analysis of the binding indicated the presence of a single class of high-affinity binding sites with a dissociation constant of 5.00 +/- 0.96 nmol/L, a maximal binding of 22.85 +/- 2.71 fmol/10(6) cells and 13.80 +/- 1.60 x 10(3) binding sites per cell. The addition of a cyclooxygenase inhibitor, indomethacin, during the cell preparation increased the maximal binding value and the number of binding sites of 37.34 +/- 3.01 and 22.50 +/- 1.80 x 10(3) sites/cell, respectively. The binding was displaced by various thromboxane A2 analogs such as ONO-3708 and STA2 but was not effectively competed for by other prostaglandins. Endotoxin injection reduced dissociation constant, maximal binding and the number of binding sites in sinusoidal endothelial cells to 3.49 +/- 0.87 nmol/L, 6.03 +/- 0.64 fmol/10(6) cells and 3.65 +/- 0.39 x 10(3) sites/cell, respectively. A cyclooxygenase inhibitor and a Kupffer cell inhibitor added before endotoxin treatment significantly prevented the reduction in the number of thromboxane A2 receptors. It is possible that these effects were due to a reduction in the agonist-induced internalization of the thromboxane A2 receptor brought about by the prevention of thromboxane A2 production. Preadministration of both a cyclooxygenase inhibitor and a thromboxane A2 receptor antagonist attenuated the degree of endotoxin-induced liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Immunologic activation of hepatic macrophages in septic rats: a possible mechanism of sepsis-associated liver injury.

To investigate the pathogenesis of liver dysfunction accompanying intra-abdominal sepsis, we used rats with cecal ligation and punctures (CLP) and examined the expression of the inflammatory cytokines IL-1-alpha, IL-1-beta, and TNF-alpha, as well as the expression of a cell adhesion molecule, ICAM-1, in the liver. We also examined the expression of Ia antigen and interleukin-2 receptor (IL-2R) on hepatic macrophages. Hepatic macrophages isolated from rats 24 hours after CLP exhibited significantly higher IL-1 and TNF activity than those from control rats. Hepatic macrophages isolated from rats 72 hours after CLP exhibited the maximal IL-1 and TNF activity. In the hepatic nonparenchymal cells, IL-1-alpha mRNA was induced 1 hour after CLP, increasing to the maximal level 3 hours after CLP, whereas IL-1-beta mRNA was induced gradually, reaching a peak 6 hours after CLP. ICAM-1 mRNA reached a peak 3 hours after CLP. Induction of TNF-alpha mRNA was not detected by the present Northern blot analysis. Seventy-two hours after CLP, the proportions of hepatic macrophages expressing Ia antigens and IL-2R were increased significantly, as revealed by the flow cytometric analysis. In conclusion, the present study showed that hepatic macrophages are in an activated state in sepsis as indicated by their increased production of inflammatory monokines and their increased expression of immunomodulatory surface molecules. Further, we demonstrated the sequential induction of the mRNA of the various inflammatory cytokines and ICAM-1. These findings strengthen the notion that these cytokines are relevant to the pathogenesis of liver injury associated with sepsis.

Animals↗
PubMed1993

The role of Kupffer cells in the surveillance of tumor growth in the liver.

The present study was designed to investigate the role of Kupffer cells (Kc) in the surveillance of liver tumors. We examined the antitumor activity of Kc by 51Cr releasing assay and inhibition of [3H]thymidine ([3H]TdR) incorporation into tumor cells. We also studied the change in the growth of liver tumors following the activation and the blockade of Kc. The cytotoxicity of Kc against K562 increased as the effector:target (E:T) ratio rose and reached its maximum level of about 18% at an E:T ratio of 20:1. [3H]TdR incorporation into target cells (P815 and AH130) was also inhibited by Kc. Such antitumor activity of Kc was augmented by OK432 (K562, from 13.8 +/- 5.6 to 21.9 +/- 2.5%; AH130, from 19.2 +/- 14.5 to 37.1 +/- 12.6%). In the experiment of the inoculation of AH130 via the portal vein, OK432 decreased the number of hepatic foci, whereas macrophage inhibitors carrageenan and gadolinium increased the number of tumor nodules. In addition, gadolinium injection reduced the number of Kupffer cells reactive with monoclonal antibodies directed against macrophages ED2 and Ki-M2R. Tumor growth in the liver was maximum in rats with both gadolinium treatment and splenectomy. In conclusion, Kc have antitumor activity, and augmentation of Kc may be a possible strategy to prevent hematogenous hepatic metastasis.

Animals↗
PubMed1992

Comparison of the modes of action of a Vero toxin (a Shiga-like toxin) from Escherichia coli, of ricin, and of alpha-sarcin.

The modes of action of a Vero toxin (VT2 or Shiga-like toxin II) from Escherichia coli, of ricin, and of alpha-sarcin were compared. Elongation factor 1 (EF1) and GTP-dependent Phe-tRNA binding to ribosomes in the presence of poly(U) was inhibited by these three toxins, but EF1 and guanylyl (beta, gamma-methylene)-diphosphate-dependent Phe-tRNA binding was inhibited by alpha-sarcin only. EF1- and Phe-tRNA-dependent GTPase activity was inhibited by these toxins, but nonenzymatic binding of Phe-tRNA was not. The turnover rate of EF1 binding to ribosomes during Phe-tRNA binding was also decreased by these three toxins. The addition of EF1 recovered the inhibition of Phe-tRNA binding to ribosomes by VT2 and ricin but not by alpha-sarcin. The formation of and EF2- and GTP-dependent puromycin derivative of phenylalanine was inhibited slightly by the three toxins, indicating that translocation is not influenced significantly by them. EF2-dependent GTPase activity was stimulated by these toxins, and especially by VT2 and ricin. In contrast, the binding of EF2 to ribosomes was inhibited strongly by VT2 and ricin, and slightly by alpha-sarcin. The stimulation of EF2-dependent GTPase activity by the toxins may compensate for the decrease of EF2 binding to ribosomes which they caused during translocation. In total, these results indicate that VT2 and ricin inhibit protein synthesis through the disturbance of the turnover of EF1 binding to ribosomes during aminoacyl-tRNA binding to ribosomes, and that alpha-sarcin inhibits the synthesis through the inhibition of the binding of the complex of Phe-tRNA, EF1, and GTP to ribosomes.

Animals↗
PubMed1992

Tumoricidal activity of Kupffer cells augmented by anticancer drugs.

The effect of Mitomycin-C (MMC) and Adriamycin (ADM) on the antitumor-associated function of Kupffer cells was examined. MMC and ADM enhanced the production of superoxide by Kupffer cells in cultures at low concentrations likely to occur in clinical use. The expression of interleukin-2 receptor, Ia antigen and asialoGM1 antigen, measured by flowcytometry, was increased by contact with MMC. Growth inhibition of AH130, rat ascites hepatoma, and P815, murine mastocytoma, by Kupffer cells treated with anticancer drugs was greater than that by Kupffer cells alone or anticancer agent alone. These results show that MMC and ADM activate Kupffer cells, leading to synergistic antitumor activity. The results suggest that some anticancer agents act through immunological mechanisms as well as through direct antineoplastic activity.

Animals↗
PubMed1992

Effect of PGE2 on interleukin-1 and superoxide release from primary-cultured human hepatic macrophages.

In order to learn more about how human hepatic macrophages function, we analyzed the effect of exogenous PGE2 on the amounts of interleukin-1 (IL-1) and superoxide (O2-) released from primary-cultured human hepatic macrophages (HHM phi). When endogenous PGE2 production was blocked by indomethacin, exogenous PGE2 reduced IL-1 release from HHM phi in a dose-dependent manner, whereas it tended to increase O2- release from HHM phi. These results may suggest the probable contribution of PGE2 in regulating HHM phi mediator release in vivo.

Cells, Cultured↗
PubMed1992

Hepatic macrophage malfunction in rats with obstructive jaundice and its biological significance.

The present study was designed to investigate the pathophysiology of obstructive jaundice by analyzing the function of hepatic macrophages and their role in immune responses and homeostasis in rats. The phagocytic index, determined by the rate of disappearance of 51Cr-endotoxin from the peripheral blood after intravenous injection, was increased in obstructive jaundice 2 weeks after bile duct ligation. The superoxide production of isolated hepatic macrophages and peripheral blood monocytes, measured by the superoxide dismutase inhibitable ferricytochrome c reduction method, was increased. Prostaglandin E2 release, measured by RIA, was markedly increased in rats with obstructive jaundice, but there was no significant difference in interleukin-1 release between jaundiced and control rats. The flow-cytometric analysis of surface molecules of hepatic macrophages showed decreased expression of interleukin-2 receptor in rats with obstructive jaundice. Thus, the functions of hepatic macrophages in rats with obstructive jaundice were impaired. This malfunction may disturb the immunoregulatory network and metabolism, although the exact implications of the altered function of hepatic macrophages have not yet been clarified.

Animals↗
PubMed1991

Complete sequence of human cardiac alpha-myosin heavy chain gene and amino acid comparison to other myosins based on structural and functional differences.

We have obtained the 5820 nucleotide sequence encoding all 1939 amino acids of the human cardiac alpha-myosin heavy chain (alpha-MHC), as established by dideoxy sequencing of cloned cDNA, genomic DNA and polymerase chain reaction (PCR) amplification products. This sequence represents overlapping fragments of the entire coding sequence. Amino acid sequence comparison of the human cardiac alpha-MHC with the published human cardiac beta-MHC have demonstrated that there are, at least, 7 isoform-specific divergent regions, including functionally important binding protein-related sites such as ATP, actin and myosin light chain. It has been reported that in the rat, there are 8 isoform-specific divergent regions. The 7th divergent area (residue area 1633-1657, which is thought to mediate thick filament formation) in the light meromyosin region in the rat is not apparent in the human. The amino acid compositions of cardiac alpha- and beta-MHCs in the human and the rat, and human embryonic skeletal muscle and chicken gizzard smooth muscles were compared. Amino acid sequences in cardiac alpha- and beta-MHCs in the human and the rat are well conserved. In the head portion, the amino acid composition divergence of human cardiac alpha-MHC is ranked between rat cardiac alpha-MHC and human cardiac beta- or rat cardiac beta-MHC; human skeletal muscle MHC is the most divergent of the myosin isoform examined. These data predict that human cardiac alpha-MHC may have undergone evolutionary changes toward obtaining the biochemical and physiological properties of cardiac beta-MHC.

Amino Acid Sequence↗
PubMed1991

Importance of arginine at position 170 of the A subunit of Vero toxin 1 produced by enterohemorrhagic Escherichia coli for toxin activity.

Comparison of the primary structures of the A subunits of Vero toxin 1 (VT1), Vero toxin 2 (VT2), and two variants of VT2 (VT2vp and VT2vh) and the ricin A chain revealed three conserved regions (amino acid residues 51-55, 167-171 and 202-207 from the N-terminus of VT1). All three regions of the ricin A chain corresponded in position to the active site of ricin proposed by X-ray crystal diffraction analysis. To determine the relative importance of the conserved amino acid residues for toxin activity of VT1, we prepared VT1 mutants with single amino-acid substitutions by oligonucleotide-directed site-specific mutagenesis. A total of 22 mutants were prepared to examine 14 conserved residues, and their cytotoxicities to Vero cells and inhibitory activities on protein synthesis in a rabbit reticulocyte lysate were compared with those of wild-type VT1. Replacement of glutamic acid at position 167 by glutamine and of arginine at position 170 by leucine reduced both activities drastically. These results suggest that, in addition to the glutamic acid at position 167 reported previously, arginine at position 170 also plays an important role in the toxin activity of VT1. A possible chemical mechanism of the enzymatic (N-glycosidase) activity of VT1 is proposed based on the relative activities of various mutants.

Amino Acid Sequence↗
PubMed1991

[A case report of liver metastasis from rectal cancer effectively treated with intravenous infusion of cisplatin alone].

A 49-year-old man with liver metastasis from rectal cancer was treated with cisplatin (CDDP) alone. Cisplatin was administered intravenously 3 times at a dose of 50 mg (31 mg/m2). He achieved an excellent PR (94% decrease) as determined by CT scanning, and plasma CEA level decreased from 37 to 2.2 ng/ml. The side effects were nausea, vomiting, and reflux esophagitis, but neither leucopenia nor renal dysfunction was observed. As a result, a radical operation could be undertaken.

Adenocarcinoma↗
PubMed1990

Demonstration of RNA N-glycosidase activity of a Vero toxin (VT2 variant) produced by Escherichia coli O91:H21 from a patient with the hemolytic uremic syndrome.

A new Vero toxin purified from Escherichia coli O91:H21 isolated from a patient with the hemolytic uremic syndrome (VT2vh) was shown to inhibit elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes, resulting in inhibition of protein synthesis in rabbit reticulocytes. VT2vh, like Shiga toxin, VT1 and VT2, showed RNA N-glycosidase activity and cleaved the N-glycosidic bond of the adenosine residue at position 4324 in 28S ribosomal RNA.

Animals↗
PubMed1989

Polymorphism of T-cell receptor genes among laboratory and wild mice: diverse origins of laboratory mice.

Southern blots of genomic DNA from 23 strains of laboratory mice and 19 individual wild mice were examined for restriction fragment length polymorphisms in their loci encoding the T-cell receptors (Tcr): the constant regions of the alpha, beta, and gamma chains (C alpha, C beta, and C gamma) and a variable region family of the beta chain (V beta 8). Only a few polymorphisms were observed for each locus in the laboratory mice after using three restriction enzymes, Bam HI, Eco RI, and Hind III. All the laboratory mice examined fall into one of two types for the C alpha, C beta, and V beta 8 loci and one of three types for the C gamma. These types are found in some of the wild mice studied, indicating that they were already present in the founder mice of laboratory mouse strains. In contrast, the Tcr genes are highly polymorphic among wild mice. Analysis of the polymorphisms in these loci suggests that laboratory mice have inherited their genes not only from Mus musculus domesticus, but also from other subspecies, and much more than previously believed from Asian subspecies.

Animals↗
PubMed1989

Post-transcriptional allelic exclusion of two functionally rearranged T cell receptor alpha genes.

We cloned and sequenced T cell receptor (TCR) alpha and beta chain cDNA from a lambda gt10 library obtained from a murine I-Ak autoreactive helper T cell clone MS202. Two types of cDNA clones for the alpha chain and one for the beta chain were obtained. The two alpha chain transcripts used two different V alpha genes: V alpha 4, joined to J alpha 11.2; and V alpha 5, J alpha TA13. The four V alpha 4 cDNA clones obtained did not have a complete sequences, lacking the leader portion. The V alpha 4 genomic gene segment of MS202 was revealed to contain two exons corresponding to the V alpha 4.MD13 cDNA sequence, and the potential RNA splicing signals between the two exons were intact. Both of the alpha chain cDNA clones showed in-frame rearrangements. Immunoprecipitation of 125I-surface-labeled lysate of MS202 with anti-TCR antiserum and subsequent electrophonetic analyses indicated that only one of the alpha chain polypeptides was expressed on the cell surface. Thus, allelic exclusion of the alpha chain in MS202 is achieved by post-transcriptional regulation rather than rearrangements.

Alleles↗
PubMed1989

[Study of organisms isolated from non-infected patients with pneumoconiosis].

Studies on the sputum organisms and their seasonal incidences were conducted on non-infected patients with pneumoconiosis. A total of 3318 organisms were isolated from 1427 sputum examinations, an average of 4 examinations per patient. alpha-Streptococcus, GPC, Neisseria and GNC were isolated in 74.1, 22.1, 64.8, 21.3% of the patients respectively. In addition, organisms to cause respiratory infection were isolated in the non-infected phase. S. pneumoniae, S. aureus, B. catarrhalis, H. influenzae, E. coli, K. pneumoniae and P. aeruginosa were isolated in 1.5, 5.1, 2.5, 3.3, 2.9, 6.4, 2.8% of the patients respectively. Studies of the seasonal incidences in these organisms showed that H. influenzae, B. catarrhalis and S. pneumoniae were isolated mostly in winter, S. aureus mostly in spring, E. coli and K. pneumoniae mostly in summer. On the other hand, P. aeruginosa showed no seasonal incidence. In relation to the causing organisms of respiratory infection with pneumoconiosis, it is very interesting that many organisms were isolated in the non-infected phase, and seasonal incidences were observed.

Humans↗
PubMed1989

[Long-term administration of tegafur in postoperative adjuvant chemotherapy in gastric cancer patients. Serial analysis of serum tegafur and 5-fluorouracil concentrations, and influence from PSK combination].

We investigated the pharmacokinetics of long-term (2-year) daily oral administration of FT-207-E or UFT for postoperative adjuvant chemotherapy in 85 gastric cancer patients by measuring serum FT-207 and 5-FU concentration serially. There were no significant changes in serum FT-207.5-FU concentration during observation period between FT-207-E and UFT groups. There was different operative modality between partial gastrectomy (Billroth I) and total gastrectomy, but no significant difference in serum FT-207.5-FU concentration between the two groups, and no significant serial changes in serum FT-207.5-FU concentrations were observed in both groups. Conversion from FT-207 to 5-FU measured by serum concentration was not suppressed by combination with the biological response modifier PSK.

Adjuvants, Immunologic↗
PubMed1988

A simple purification method for a glucosyltransferase complex from Streptococcus mutans OMZ 176 with a high yield.

1. Glucosyltransferase was purified from Streptococcus mutans OMZ 176 by ammonium sulfate fractionation and gel filtration. 2. The overall purification was about 15,000-fold with a yield of 53%. 3. The purified enzyme appeared to be a multienzyme complex consisting of three different components with molecular weights of 158,000, 153,000 and 149,000, respectively.

Ammonium Sulfate↗
PubMed1988

[A correlation between the evaluation of assay results of immuno-suppressive substance (IS) in the blood and other parameters in patients with gastric cancer].

This present study has assayed the immuno-suppressive substance (IS) in the blood level at certain definite times in patients with a gastric cancer. Prior to surgery, the positivity of IS was low in Stages I and II but rose rapidly with the advance in stage. Therefore this assay has little meaning as a method for screening the cancer. Two months after operation, a loss in the IS amount occurred, due to the therapeutic treatment that had been initiated, and a state of equilibrium was reached after the third month. This IS withdrawal from the blood was delayed in comparison with other parameters. Further, a mild negative correlation was observed between the IS blood levels and the PPD intracutaneous reaction, which was determined in parallel, while a moderately positive correlation was found between the IS blood levels and the levels of the tissue polypeptide antigen and the alpha 2-globulin in the blood. The determination of the IS blood levels at specific times has been deemed useful and should be done in combination with the evaluation of the other parameters, which have different mechanisms of formation, so as to ascertain the general condition of the cancer patient.

Adult↗