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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 685 records · Page 38Linked to original sources
PubMed1996

Hepatic hemorrhage in malignant rheumatoid arthritis.

Intrahepatic hemorrhage is a serious and life-threatening complication in liver disease. We describe a patient who had two episodes of intrahepatic hemorrhage after having malignant rheumatoid arthritis for 8 yr. Abdominal CT scans revealed a large intrahepatic, subcapsular hematoma. Arteriography demonstrated irregularity, caliber change, and pseudoaneurysms of the right hepatic artery, suggesting vasculitis as a cause of the bleeding. The hemorrhage was first treated with transcatheter arterial embolization, which failed to exert long term control, but arterial infusion of a large dose of prednisolone when the hemorrhage appeared was successful in managing it.

Adult↗
PubMed1995

Regulation of rat liver type 1 iodothyronine deiodinase mRNA levels by testosterone.

To investigate the underlying mechanisms of sex-related differences in liver type 1 iodothyronine deiodinase (ID1), we studied the sex-related differences and roles of sex steroids in liver ID1 mRNA levels in the rat. In both euthyroid and thyroidectomized rats, liver ID1 activity and ID1 mRNA levels in female rats were less than those in male rats. A positive correlation was observed between liver ID1 activity and ID1 mRNA levels. Liver ID1 activity and ID1 mRNA levels in male rats decreased after orchiectomy, and were increased to control levels by testosterone administration. Ovariectomy of beta-estradiol administration did not alter liver ID1 activity or ID1 mRNA levels in female rats. ID1 mRNA levels in cultured rat hepatocytes were significantly increased by testosterone, but not by beta-estradiol. These results suggest that the sex-related differences in liver ID1 activity are attributable to differences in ID1 mRNA levels, and that testosterone plays an important role in the sex-related differences in liver ID1 mRNA levels.

Animals↗
PubMed1995

Human REG family genes are tandemly ordered in a 95-kilobase region of chromosome 2p12.

Reg, first isolated from a rat regenerating islet cDNA library, is expressed in regenerating islet beta-cells. Recently, it has been revealed that Reg and Reg-related genes constitute a multigene family, the Reg family. In human, the four REG family genes, i.e., REG 1 alpha, REG 1 beta, REG-related sequence (RS) and HIP/PAP, have so far been isolated. In this study, we analyzed YAC clones containing the four genes and performed two-color FISH to determine the map order of the genes. The human REG family genes are tandemly ordered in the 95-kbp DNA region of chromosome 2p12 as follows: 2cen-HIP/PAP-RS-REG I alpha-REG I beta-ptel.

Acute-Phase Proteins↗
PubMed1995

Effects of dibutyryl guanosine 3',5'-cyclic monophosphate and sodium nitroprusside in pepsinogen secretion from guinea pig chief cells with respect to intracellular Ca2+.

Both Ca2+ and adenosine 3',5'-cyclic monophosphate act as intracellular second messengers in pepsinogen secretion from chief cells. However, the role of intracellular guanosine 3',5'-cyclic monophosphate (cGMP) in this process has not been defined. Although dibutyryl cGMP (dbcGMP), a membrane-permeable derivative of cGMP, has been shown to inhibit pepsinogen secretion only stimulated by cholecystokinin (CCK), the intracellular mechanism of this effect remains unclear. We evaluated the role of intracellular cGMP in pepsinogen secretion from monolayer cultured guinea pig chief cells using dbcGMP and sodium nitroprusside, both of which increase intracellular cGMP. Dibutyryl cGMP and sodium nitroprusside have now been shown to inhibit pepsinogen secretion induced by not only CCK octapeptide but also carbamylcholine chloride and ionomycin in a dose-dependent manner. Furthermore, dbcGMP reduced the increase in intracellular free Ca2+ concentration induced by carbamylcholine chloride, CCK octapeptide, and ionomycin. These results suggest that intracellular cGMP may inhibit pepsinogen secretion by reducing the intracellular free Ca2+ concentration.

Animals↗
PubMed1995

Mediation of pepsinogen secretion from guinea pig chief cells by Ca2+/calmodulin-dependent protein kinase II.

In the presence of Ca2+ bound to calmodulin, Ca2+/calmodulin-dependent protein kinase II (CaMK II) exhibits an intramolecular autophosphorylation and modulates many cell functions. In this study, the role of CaMK II in pepsinogen secretion was investigated in cultured guinea pig chief cells by using a specific CaMK II inhibitor, 1-[N,O-Bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpipera zin e (KN-62), and an antibody for the Thr-286-autophosphorylated alpha subunit of CaMK II which specifically recognized the autophosphorylated form of CaMK II. KN-62 inhibited the pepsinogen secretion stimulated by carbamylcholine chloride, cholecystokinin octapeptide, and ionomycin in a dose-dependent manner without affecting intracellular Ca2+ concentrations, but had no effect on the secretion by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and forskolin. Heavy staining with the antibody for autophosphorylated CaMK II was observed in the cytoplasm of chief cells treated with carbamylcholine chloride or ionomycin, but only light staining was seen in cells treated with TPA or forskolin. Thus, CaMK II and its autophosphorylation may be a critical step in the intracellular pathway in which Ca2+ causes pepsinogen secretion from guinea pig chief cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Nonisotopic receptor assay for benzodiazepine drugs using time-resolved fluorometry.

A nonisotopic receptor assay for benzodiazepine drugs using a time-resolved fluorometric technique is described. A novel europium chelate-labeled benzodiazepine (Eu-1012-S) was prepared as a probe ligand for the binding assay based on the competitive inhibition of Eu-1012-S binding by benzodiazepine drugs to their receptors. In this system, the degree of the inhibition was proportional to the affinity of drugs for the receptor. Background fluorescence did not interfere with the measurement, due to the long-lifetime fluorescence of Eu-1012-S. The proposed nonisotopic assay may provide an alternative to radioreceptor assays of benzodiazepines in biological systems and could also be used to screen new benzodiazepine-like compounds from nature.

Animals↗
PubMed1995

Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation.

A mouse mutation, termed jumonji (jmj), was generated by a gene trap strategy. Expression of the trapped gene (jmj gene), as monitored by X-gal staining, was detected predominantly at the midbrain-hindbrain boundary and in the cerebellum, depending on the stage of development. All embryos homozygous for the jmj mutation died before embryonic day 15.5. Some, but not all, of the homozygotes developed an abnormal groove in a region just anterior to the midbrain-hindbrain boundary on the neural plate at embryonic day 8-8.5 and showed a defect in neural tube closure in the midbrain region. Analyses of jmj cDNA revealed that the jmj gene is novel, conserved among vertebrates, and disrupted by vector insertion in the jmj homozygotes. The amino acid sequence deduced from the cDNA shared a portion of significant homology with human retinoblastoma-binding protein RBP-2 and with a putative protein encoded by human gene XE169 that escapes X-chromosome inactivation. These results suggest that jmj gene is essential for normal morphogenesis of the neural tube.

Amino Acid Sequence↗
PubMed1995

Biochemical and molecular characterization of nucleoside triphosphate hydrolase isozymes from the parasitic protozoan Toxoplasma gondii.

We have previously reported the presence of a novel nucleoside triphosphate hydrolase (NTPase) in the rapidly multiplying tachyzoite form of a virulent strain (RH) of Toxoplasma gondii. On further examination, it was found that the purified enzyme was not a single enzyme but was a mixture of two isozymes termed NTPase-I and NTPase-II. The two isozymes had similar molecular masses of approximately 240-270 kDa by gel filtration and contained four identical subunits of molecular mass 66-67 kDa by SDS-polyacrylamide gel electrophoresis. Both forms of the NTPase were activated by dithiothreitol, and NTPase-I had a specific activity 4.5-fold higher than NTPase-II in hydrolysis of ATP. The primary difference between these isozymes lies in their ability to hydrolyze nucleoside triphosphate versus diphosphate substrates. While NTPase-II hydrolyzed ATP to ADP and ADP to AMP at almost the same rate, NTPase-I hydrolyzed ADP to AMP at a much slower rate (0.7% of the rate for ATP). The complete cDNAs for NTPase-I and NTPase-II were sequenced and found to encode the same size predicted open reading frame of which only 16 of 628 amino acids differed between the two isozymes. Both forms of the NTPase contained an NH2-terminal hydrophobic signal peptide, consistent with our previous findings that these enzymes are secreted into the host cell vacuole occupied by the parasite. The gene encoding NTPase-II was found in all strains of Toxoplasma, while the NTPase-I was confined only to virulent strains. Expression of this highly active ATPase (NTPase-I) may contribute to intracellular survival and virulence of T. gondii.

Acid Anhydride Hydrolases↗
PubMed1995

Ca(2+)-independent fusion of secretory granules with phospholipase A2-treated plasma membranes in vitro.

The fusion of secretory granules with plasma membranes prepared from rat parotid gland was studied in vitro to clarify the mechanism of exocytosis. Fusion of the granules with plasma membranes was measured by a fluorescence-dequenching assay with octadecyl rhodamine B, and release of amylase was also measured to confirm the fusion as a final step of the secretory process. Plasma membranes that had been pretreated with porcine phospholipase A2 (PLA2) in the presence of 20 microM Ca2+ fused with the granules within 30 s, and induced amylase release by reacting with the membranes of granules, whereas without this pretreatment they had no significant effect. The fusion process accompanied by amylase release was induced in the presence of 10 mM EGTA, and therefore was apparently Ca(2+)-independent. On the other hand, the presence of EGTA or 100 microM quinacrine, an inhibitor of PLA2, during treatment of plasma membranes with PLA2 inhibited their fusogenic activity, suggesting the importance of activation of PLA2. Arachidonic acid and linoleic acid were released from the plasma membranes during the PLA2 treatment. The presence of albumin, an adsorbent of fatty acids, during the treatment also inhibited the activity. Pretreatment of the membranes with arachidonic acid or linoleic acid did not have any effect, but the presence of exogenously added arachidonic acid during PLA2 treatment enhanced the membrane-fusion-inducing effect of PLA2. Pretreatment of the membranes with lysophosphatidylcholine induced fusogenic activity. These findings suggest that the conformational change in the plasma-membrane phospholipids induced by PLA2 and the presence of arachidonic acid or linoleic acid produced by PLA2 are important in the process of fusion of secretory granules with the plasma membranes of rat parotid acinar cells and that the fusion process itself is independent of Ca2+.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1995

Comparative studies on bile flow and biliary lipid excretion after bile-acid loading in normal and partially hepatectomized rats.

This study was performed to investigate sequential changes in bile secretion and biliary lipids after taurocholic acid (TCA) loading of regenerating rat liver. TCA was administered intravenously at stepwise-increasing doses to groups of non-operated control and partially hepatectomized rats, 24, 72 and 168 h after surgery. Bile flow, bile-acid output (BAO) and phospholipid output (PLO) (expressed per gram of liver) in partially hepatectomized rats increased more than in the controls. Using an isolated perfusion rat-liver system, TCA infusion was also carried out on groups of non-operated control and hepatectomized rats 72 h after operation. Again bile flow, BAO and PLO (expressed per gram of liver) were significantly higher in the partial hepatectomy case, mirroring the results obtained in vivo. When horseradish peroxidase (HRP) was pulse-loaded in isolated perfusion preparations, the second peak of biliary HRP secretion in hepatectomized rats was significantly higher than in controls. We conclude that increased bile-acid flow in partially hepatectomized rats is dependent upon acceleration of vesicular transport accompanying or following proliferation in regenerating livers.

Animals↗
PubMed1995

Antitumor antibiotics discovered and studied at the Institute of Microbial Chemistry.

In 1951, we were pioneers in initiating screening of antitumor agents from microbial metabolites. We discovered bleomycin in 1962 and aclacinomycin in 1975. Peplomycin, a derivative of bleomycin, and pirarubicin, a tetrahydropyranyl derivative of doxorubicin, were also studied. All of them have been clinically used for the treatment of cancer. Using new screening methods, we isolated spergualin in 1982. This agent exhibited immunosuppressive activity as well as antitumor activity. Deoxyspergualin, a derivative of spergualin, is now clinically used for the treatment of acute rejection after kidney transplantation. Bestatin was screened as an inhibitor of aminopeptidase B in 1976. It binds to the aminopeptidases located on the cell membrane of immunocompetent cells and modulates immune responses. It is now used for the treatment of acute non-lymphocytic leukemia. Microbial metabolites will become more important as a source of anticancer drugs in the future.

Academies and Institutes↗
PubMed1995

Systemic lupus erythematosus with necrotizing vasculitis and upregulated expression of VLA-4 antigen.

We report on a patient (S.A.), with well-defined SLE who developed a perforation of the ileum due to pathologically confirmed necrotizing vasculitis. No anti-DNA antibody was detected at the ileal perforation, and the serum complement level was normal. These findings raise the alternative possibility of a cell-mediated immune mechanism as a cause of necrotizing vasculitis. Upregulated expression and function of VLA-4 antigen on peripheral blood T cells were observed, suggesting that T cells with VLA-4 antigen may participate in the onset and/or perpetuation of vascular inflammation.

Adult↗
PubMed1995

Chronic pancreatitis caused by an autoimmune abnormality. Proposal of the concept of autoimmune pancreatitis.

Several authors have reported a case of chronic pancreatitis associated with Sjögren's syndrome in which an autoimmune mechanism may have been involved in the etiology and in which steroid therapy was effective. We recently encountered a patient with pancreatitis who had hyperglobulinemia, was autoantibody-positive, and responded to steroid therapy. This patient, however, failed to show any evidence of association with Sjögren's syndrome or other collagen diseases. Although the concept of autoimmune hepatitis and the criteria for diagnosing it have been established, autoimmune pancreatitis has not yet been defined as a clinical entity. We report a case of chronic pancreatitis in which an autoimmune mechanism is involved in the etiology and summarize the cases of pancreatitis suspected of being caused by an autoimmune mechanism in the Japanese and English literature.

Aged↗