Congenital factor XII deficiency and lupus anticoagulant.
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Adult↗
Biomedical subjects
Y Endo
Publications and source records attributed to Y Endo.
[Regulation of histamine-forming enzyme by cytokines].
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Animals↗
Biophysical parameters of glucocorticoid-binding proteins from rat inflammatory tissues.
The complexes of [3H]glucocorticoid and cytoplasmic proteins of the inflammatory tissue were characterized by the gel filtration and by the sucrose density gradient centrifugation. Protein-bound [3H]cortisol sedimented at about 4 S with a Stokes radius of about 4 nm and an apparent molecular weight (Mr) of about 70 kDa, irrespective with the presence of 0.4 M KCl. The complex of [3H]triamcinolone acetonide (TAA) and protein sedimented at about 7 S and showed about 170 kDa of Mr and about 6 nm of the Stokes radius in the absence of 0.4 M KCl. In the presence of 0.4 M KCl, the [3H]TAA-protein complex changed into a smaller form (4 S) with about 4 nm of the Stokes radius and about 60 kDa of Mr. This suggests that the so-called glucocorticoid receptor of the inflammatory tissue associates with a 110 kDa protein.
Animals↗
High-level expression of hepatitis B virus HBx gene and hepatocarcinogenesis in transgenic mice.
We studied the development of liver tumors in male HBx gene transgenic mice. Of two lineages studied, in the lineage with the lowest HBx gene expression liver tumors developed only in an incidence comparable with that in normal CD-1 strain, whereas 84% of male mice with a high level of the HBx gene product succumbed to liver neoplasia, indicating that continued HBx gene expression higher than a certain threshold level may be necessary for the development of hepatic neoplasia. Sixty-five mice from a lineage with a high level of HBx expression were then followed throughout their 24-mo lifespan. The livers of transgenic mice showed foci of cellular alteration with cytoplasmic vacuolations around the central veins from the age of 2 mo, but these foci did not expand progressively by the age of 12 mo. Immunostaining demonstrated such hepatocytes had higher expression of HBx protein than surrounding cells. Neoplastic lesions including liver cell adenomas and hepatocellular carcinomas developed from the age of 13 mo. By bromodeoxyuridine labeling analysis, hepatocytes in altered foci were found to have increased DNA synthesis, whereas no labeling was observed in age- and sex-matched nontransgenic littermate controls. Furthermore, DNA content analysis revealed the existence of several small aneuploid peaks in the transgenic liver before the age of tumor development. These results suggest that the continued expression of HBx gene may initiate a complex process to hepatocellular carcinoma by inducing DNA synthesis and placing large numbers of hepatocytes subjective to secondary events for transformation.
Adenoma, Liver Cell↗
Hepatocellular carcinoma with splenic metastasis developing after 16 years of chemotherapy for chronic myelogenous leukemia: a case report.
A case of hepatocellular carcinoma (HCC), which developed during chemotherapy for chronic myelogenous leukemia (CML), is presented. A 55-year-old Japanese man, who had received an alkylating agent for 16 years, was diagnosed as having HCC with clinically evident splenic metastases. The patient died of the HCC rupture three months after diagnosis. The autopsy revealed the HCC to have developed from the non-cirrhotic liver. In the present case, DNA damage due to the long-term chemotherapy with the alkylating agent for CML may have endowed the HCC induced by post-transfusion hepatitis and alcohol abuse with an aggressive proliferative potential. This is the first report on HCC in association with CML.
Busulfan↗
High-resolution NMR study of a synthetic oligoribonucleotide with a tetranucleotide GAGA loop that is a substrate for the cytotoxic protein, ricin.
Ricin is a cytotoxic protein that inactivates ribosomes by hydrolyzing the N-glycosidic bond at position A4324 in eukaryotic 28S rRNA. Its substrate domain forms a double helical stem and a 17-base loop that includes the sequence GAGA, the second adenosine of which corresponds to A4324. Recently, studies of mutant RNAs have shown that the four-nucleotide loop, GAGA, can function as a substrate for ricin. To investigate the structure that is recognized by ricin, we studied the properties of a short synthetic substrate, the dodecaribonucleotide r-CUCAGAGAUGAG, which forms a RNA hairpin structure with a GABA loop and a stem of four base pairs. The results of NMR spectroscopy allowed us to construct the solution structure of this oligonucleotide by restrained molecular-dynamic calculations. We found that the stem region exists as an A-form duplex. 5G and 8A in the loop region form an unusual G:A base pair, and the phosphodiester backbone has a turn between 5G and 6A. This turn seems to help ricin to gain access to 6A which is the only site of depurination in the entire structure. The overall structure of the GAGA loop is similar to those of the GAAA and GCAA loops that have been described but that are not recognized by ricin. Therefore, in addition to the adenosine at the depurination site, the neighboring guanosine on the 3' side (7G) may also play a role in the recognition mechanism together with 5G and 8A.
Base Composition↗
A collaborative study for the evaluation of lectin-reactive alpha-fetoproteins in early detection of hepatocellular carcinoma.
Lectin-affinity electrophoretic separation of serum alpha-fetoprotein (AFP) was carried out using AFP Differentiation Kits, which used Lens culinaris agglutinin-A (Kit L) and erythroagglutinating phytohemagglutinin (Kit P). Separated AFP bands were detected with a sensitive antibody-affinity blotting technique and determined quantitatively by densitometry, and the results were expressed as percentages of the intensity of total AFP bands. Sera from 424 patients with acute hepatitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and extrahepatic tumors were assayed for proportion of AFP present as Lens culinaris agglutinin-A-reactive AFP (AFP-L3) and erythroagglutinating phytohemagglutinin-reactive AFPs (AFP-P4+P5). From the maximum Youden indices determined, cutoff levels were set at 15% for both AFP-L3 and AFP-P4+P5 to discriminate between patients with chronic hepatitis and liver cirrhosis and patients with hepatocellular carcinoma. AFP-L3 and AFP-P4+P5 showed sensitivities of 55.3 and 61.0% at specificities of 93.9% and 82.3%, respectively. Thirty-eight % of tumors that measured less than 20 mm in diameter were positive for AFP-L3 and AFP-P4+P5. AFP-L3 exceeded the cutoff level of 15% 4.0 +/- 4.9 months before detection of hepatocellular carcinomas by imaging techniques with a sensitivity of 48% and a specificity of 81%. Thus, these tests are useful for the early detection of hepatocellular carcinomas in patients with hepatitis or liver cirrhosis.
Carcinoma, Hepatocellular↗
Oxygenated cholesterols as ligands for cytosolic-nuclear tumor promoter binding protein: yakkasteroids.
Several oxygenated cholesterols and their derivatives (yakkasteroids) were prepared as candidate ligands for cytosolic-nuclear tumor promoter binding protein (CN-TPBP). Among the compounds, a possible natural substance, 3 beta,5 alpha-dihydroxycholestan-6-one (yakkasterone), showed the highest binding affinity to CN-TPBP. It also showed high specificity for binding to CN-TPBP: it does not bind to protein kinase C. Investigation of the structure-activity relationships of yakkasteroids revealed that the structure of the side chain at the 20-position is important for the binding activity to CN-TPBP.
Binding, Competitive↗
Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein.
BACKGROUND: The sugar-chain structures of circulating alpha-fetoprotein in patients with hepatocellular carcinomas differ from those in patients with cirrhosis. We studied the reactivity of alpha-fetoprotein with two lectins, Lens culinaris agglutinin A and erythroagglutinating phytohemagglutinin, to monitor the evolution of hepatocellular carcinoma in patients with cirrhosis. METHODS: Among 361 patients with cirrhosis caused mainly by chronic hepatitis B or hepatitis C virus infection, 33 with base-line serum alpha-fetoprotein concentrations > or = 30 ng per milliliter or more were found to have hepatocellular carcinomas during a mean follow-up of 35 months. The lectin-reactive profiles of the alpha-fetoprotein in the serum of these 33 patients were analyzed and compared with those in the serum of 32 patients with cirrhosis who had increased base-line serum alpha-fetoprotein concentrations and were followed for at least 24 months but in whom hepatocellular carcinoma did not develop. RESULTS: At the time of tumor detection, 24 (73 percent) of the 33 patients with cirrhosis and hepatocellular carcinoma had higher percentages of L. culinaris agglutinin A-reactive alpha-fetoprotein (alpha-fetoprotein L3), erythroagglutinating phytohemagglutinin-reactive alpha-fetoprotein (alpha-fetoprotein P4+P5), or both than the 32 patients with cirrhosis but no hepatocellular carcinoma. Among the 24 patients, one or both of the markers were first elevated 3 to 18 months before the hepatocellular carcinoma was detected by imaging techniques. CONCLUSIONS: Measurements of the alpha-fetoprotein L3 and alpha-fetoprotein P4+P5 fractions of serum alpha-fetoprotein allow the differentiation of hepatocellular carcinoma from cirrhosis in some cases and serve as predictive markers for the development of hepatocellular carcinoma during the follow-up of patients with cirrhosis.
Adult↗
Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic disease characterized by abnormal blood cell populations in which the biosynthesis of the glycosylphosphatidylinositol (GPI) anchor is deficient. Deficiency of surface expressions of GPI-anchored complement inhibitors leads to complement-mediated hemolysis. Here we report that PIG-A, which participates in the early step of GPI anchor biosynthesis, is the gene responsible for paroxysmal nocturnal hemoglobinuria. Affected granulocytes and B lymphocytes had the same somatic mutation of PIG-A, indicating their clonal origin from a multipotential hematopoietic stem cell. We localized PIG-A to the X chromosome, which accounts for expression of the recessive phenotype of the somatic mutation and the fact that the same one of the multiple biosynthetic steps is affected in all patients so far characterized.
B-Lymphocytes↗
Tissue inhibitor of metalloproteinase 1 is a negative regulator of the metastatic ability of a human gastric cancer cell line, KKLS, in the chick embryo.
Tissue inhibitors of metalloproteinases (TIMPs) are the negative regulators of matrix metalloproteinases that degrade extracellular matrix. We examined the regulatory role of TIMP-1 in the metastatic activity of human gastric cancer cell lines in chick embryos because unregulated matrix metalloproteinase activities are believed to be essential during metastatic processes. One of the nine cell lines examined, KKLS cells, formed metastatic colonies in the chick livers. These cells expressed undetectable levels of TIMP-1, and this was not inducible by 12-O-tetradecanoylphorbol 13-acetate. Derivatives of KKLS cells with different levels of TIMP-1 expression were prepared by transfection of the human TIMP-1 complementary DNA controlled by a simian virus 40 early promoter. Metastatic abilities were suppressed by almost 70% in the transfectants expressing high levels of TIMP-1. In contrast, no suppression was observed in the control transfectants or in cells expressing the transfected TIMP-1 gene at low levels. These data indicate that a reduced expression of TIMP-1 in KKLS cells is responsible for their consequent metastatic potential. Moreover, it suggests that matrix metalloproteinase enzymatic activities are a prerequisite for metastatic activity in this experimental model system.
Animals↗
10(6) Depletion of WBC with CF-2, a new leukocyte removal filter.
A new leukocyte removal filter, Nipro CF-2, was evaluated. A non-woven polyester filter, gravity flow device that does not require priming and rinsing after use was developed to remove white blood cells from 400 ml of whole blood or concentrates of 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low WBC counts. To evaluate the efficiency of this filter, leukocyte counts were measured by flow cytometry using a Coulter EPIC-C cytometer. After filtration through a CF-2 filter, more than 99.9999% of WBCs were depleted from 6 of 17 samples. The mean value of WBC depletion was 99.9994%. The CF-2 filter achieved nearly a million-fold depletion of WBCs from whole blood concentrates.
Cell Separation↗
Effects of phospholipid adsorption on nonthrombogenicity of polymer with phospholipid polar group.
Polymers with phospholipid polar groups, 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers, have excellent nonthrombogenic properties. The effects of adsorption of phospholipids on platelet adhesion and activation on the MPC copolymer with n-butyl methacrylate (BMA) were investigated with particular attention to the structure of the phospholipids adsorbed onto the polymer surface. The electrical nature of the phospholipids adsorbed on the polymer surface affected the thrombogenicity of the polymer. On the MPC polymer surface treated with an aqueous liposomal solution of acidic phospholipids, phosphatidylserine, platelet adhesion and activation occurred to a greater extent when compared to a poly(MPC-co-BMA) surface. However, on the MPC polymer surface treated with electrically neutral phosphatidylcholines, reduced thrombogenicity could be observed. Therefore, the adsorption of the phosphatidylcholines was an important factor in reducing the thrombogenicity on the polymers. Moreover, by comparison of the poly(MPC-co-BMA) to a poly(BMA), platelet adhesion and activation on these polymer surfaces depended on the adsorption state of the phosphatidylcholines. The amount of phosphatidylcholine adsorbed on the poly(MPC-co-BMA) increased with an increase in the MPC mole fraction of the copolymer. This indicates that the MPC moieties have affinity for the phosphatidylcholines. We conclude that the poly(MPC-co-BMA) can adsorb large amounts of phosphatidylcholines and that these phospholipids organize themselves. The organized adsorption layer of the phosphatidylcholines on the surface, which construct biomembrane-like surfaces, can reduce platelet adhesion and activation effectively.
1,2-Dipalmitoylphosphatidylcholine↗
Aminoalkylbisphosphonates, potent inhibitors of bone resorption, induce a prolonged stimulation of histamine synthesis and increase macrophages, granulocytes, and osteoclasts in vivo.
Aminoalkyl derivatives of bisphosphonates are potent inhibitors of bone resorption. A single I.P. injection of 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHBuBP) induced a prolonged enhancement of histidine decarboxylase (HDC) activity in the bone marrow, spleen, lung, and liver of mice and resulted in an increase in histamine. The induction of HDC by the agent was dose dependent (16-80 mumol/kg) and peaked 3-4 days after its injection (40 mumol/kg). Repeated S.C. injections of smaller doses of AHBuBP (0.32 or 1.6 mumol/kg/day) for 4 days also enhanced HDC activity. However, the minimum dose capable of inhibiting bone resorption (0.064 mumol/kg/day) was lower than that inducing HDC. Unexpectedly, AHBuBP, at the doses inducing HDC, increased macrophages, granulocytes, and even osteoclasts. The size of osteoclasts was also enlarged by the agent. Another aminobisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate, but none of non-amino derivatives, also exhibited essentially the same effects as those of AHBuBP. These results indicate that in spite of increase in osteoclasts and their enlargement, bone resorption is still inhibited by amino bisphosphonates. As granulocyte and granulocyte-macrophage colony-stimulating factors and interleukin-3 induce HDC in hematopoietic organs, and histamine has a hematopoietic activity, the HDC induction by aminobisphosphonates may be relevant to the proliferation of progenitor cells of macrophages, granulocytes, and osteoclasts.
Alendronate↗
Effects of ridogrel on the prostacyclin-thromboxane ratio in nulliparous third trimester-pregnant rhesus monkeys.
The effects of ridogrel, a thromboxane synthetase inhibitor and endoperoxide receptor antagonist, were studied in twelve pregnant, nulliparous Rhesus monkeys (Macaca mulatta) during the last trimester of pregnancy. Ridogrel was administered intravenously in two groups of animals (n = 6), at either 0.1 mg/kg or 1.0 mg/kg. Ultrasonic assessment of the fetuses during and after the infusion period revealed no obvious changes in fetal condition. Both dosages reduced serum thromboxane levels 30 minutes after administration, 96.6% and 99.6% suppression, 0.1 mg/kg and 1.0 mg/kg, respectively (P < 0.0001), while the 1.0 mg/kg dose produced continued suppression for 24 hours (78% suppression, P < 0.0001) and was lower than the 0.1 mg/kg 24 hour value (P < 0.008). Prostacyclin levels increased to 340% and 472% of baseline values, 0.1 mg/kg and 1.0 mg/kg, respectively at 30 minutes and to 928% and 255% of baseline at 24 and 48 hours after treatment in the 1.0 mg/kg group (P < 0.0003). Ridogrel caused no changes in maternal or neonatal outcome. The potential for the use of this compound for the treatment of preeclampsia is discussed.
6-Ketoprostaglandin F1 alpha↗
Active translocation of platelets into sinusoidal and Disse spaces in the liver in response to lipopolysaccharides, interleukin-1 and tumor necrosis factor.
1. Injection of lipopolysaccharides (LPS) or endotoxin into mice and rats induces a prolonged increase in serotonin (5-hydroxytryptamine: 5HT), predominantly in the liver. 2. The 5HT increase reflects the accumulation of platelets in the sinusoidal and perisinusoidal Disse spaces (spaces between endothelial cells and hepatocytes) in the liver. 3. Most of the platelets which accumulated in these spaces still retained their intact structure and a large amount of 5HT. 4. Interleukin-1 and/or tumor necrosis factor also induce the platelet response. 5. Kupffer's cells play a key role in this platelet response. 6. Anti-platelet drugs currently used, except for anti-inflammatory steroids, were ineffective in preventing the platelet response. 7. This platelet response is different from the well known platelet aggregation. 8. The possible involvement of this platelet response in insulin-independent hypoglycaemia, disseminated intravascular coagulation, septic shock, hepatitis, Shwartzman type reactions or self-defense mechanisms is discussed.
Animals↗
Calyculin A, protein phosphatase inhibitor, enhances capacitation of human sperm.
OBJECTIVE: To examine the effects of protein phosphatase inhibitors on capacitation and protein phosphorylation in human sperm. DESIGN: The chlortetracycline (CTC) fluorescence assay was used to monitor capacitated sperm treated with or without protein phosphatase inhibitors. Capacitation was confirmed by the ability of sperm to undergo the acrosome reaction in response to Ca++ ionophore A23187 or mouse zonae pellucidae. 32P-labeled sperm phosphoproteins were analyzed by one-dimensional gel electrophoresis to detect the effects of protein phosphatase inhibitors on protein phosphorylation. RESULTS: The treatment of sperm with calyculin A resulted in the following: [1] the rapid appearance of the clear perimeter pattern, specifically, distribution of fluorescence over the entire head exhibiting a bright perimeter and bright midpiece, in a dose-dependent manner in the 1 to 100 nM range; [2] an accelerated ability to undergo the acrosome reaction; and [3] an enhanced phosphorylation of sperm phosphoproteins in a dose-related fashion in the 1 to 100 nM range. A similar stimulatory effect was observed only with a 100-fold higher concentrations of okadaic acid, another protein phosphatase inhibitor. CONCLUSION: Our results strongly suggest that protein phosphorylation and dephosphorylation may be involved in the regulation of human sperm capacitation.
Acrosome↗
Effect of epidermal growth factor on human sperm capacitation.
OBJECTIVE: To examine the effect of epidermal growth factor (EGF) on human sperm capacitation and the involvement of protein phosphorylation in the regulation of the EGF action. DESIGN: Human sperm were capacitated in modified Krebs-Ringer's bicarbonate medium of Biggers, Whitten, and Whittingham in the presence of EGF and various agents known to phosphorylate the EGF receptor. The chlortetracycline fluorescence assay was used to monitor capacitated sperm. Capacitation was confirmed by the ability of sperm to undergo the acrosome reaction in response to solubilized mouse zonae pellucidae (ZP). RESULTS: In 15 minutes, the appearance of the clear perimeter pattern increased significantly in the sperm treated with 100 ng/mL EGF compared with the controls. In EGF-treated sperm, the percent clear perimeter pattern remained stable for 3 hours without affecting the acrosome reaction pattern and the motility. Epidermal growth factor stimulated the appearance of the clear perimeter pattern at concentrations > 100 pg/mL. The stimulation by EGF was attenuated by the treatment with genistein, 12-O-tetradecanoylphorbol-13-acetate, or thapsigargin. In sperm that were incubated in the presence of 100 ng/mL EGF for 30 minutes and further induced the acrosome reaction by mouse ZP, the percent acrosome reaction pattern increased significantly compared with the controls. CONCLUSION: Epidermal growth factor stimulates human sperm capacitation by activating the tyrosine kinase of the EGF receptor which is regulated by multisite phosphorylation.
Acrosome↗