[Autologous bone marrow transplantation].
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Anti-Bacterial Agents↗
Biomedical subjects
Y Fujimori
Publications and source records attributed to Y Fujimori.
[A case of hepatocellular carcinoma with invasion into the bile duct, difficult to differentiate from cholangiocellular carcinoma: observation by endoscopic retrograde cholangioscopy and peroral cholangioscopy].
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Aged↗
[Detection of Helicobacter pylori using Ota's procedure and mucous immunohistochemistry].
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Fixatives↗
Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials.
BACKGROUND: Camptothecins belong to a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. Two camptothecin derivatives, topotecan (TPT) and CPT-11, are in clinical trials and their chemotherapeutic efficacy appears promising. PURPOSE: Our aim was to compare simultaneously the molecular and cellular pharmacology of the various camptothecin derivatives that are presently in clinical trials. METHODS: Cytotoxicity of drugs toward human colon carcinoma HT-29 cells was determined by colony-forming assays. DNA single-strand breaks (SSB) were measured by alkaline elution. Drug potency to induce topoisomerase 1-mediated DNA cleavage and the sequence selectivity of the breaks were determined by sequencing gel autoradiography. RESULTS: SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells. IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11. In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C1000), values were 0.037 microM for SN-38, 0.051 microM for CPT, 0.085 microM for 9-AC, 0.28 microM for TPT, and greater than 1 microM for CPT-11. SN-38 remained the most potent compound in isolated nuclei, and CPT-11 was still inactive. The potency ranking was the same as in whole cells, and the C1000 values were 0.0025 microM for SN-38, 0.012 microM for CPT, 0.021 microM for 9-AC, 0.44 microM for TPT, and greater than 0.1 microM for CPT-11. Potency difference between SN-38 and the other compounds was greater in isolated nuclei than in whole cells. CONCLUSIONS: Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT. Cleavage patterns of CPT and 9-AC were similar but differed from those of TPT and SN-38. Although in vitro analyses do not necessarily reflect chemotherapeutic efficacy, this study found that SN-38 is the most potent compound and that 9-AC and TPT are less active than CPT in this system. The effect of CPT-11 is minimal. Therefore, the clinical activity of CPT-11 may strongly depend on its hydrolysis to SN-38. Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives.
Camptothecin↗
The crystal and molecular structure of the trisaccharide erlose trihydrate.
Erlose [beta-D-fructofuranosyl O-alpha-D-glucopyranosyl-(1-->4)-D-glucopyranoside] trihydrate, C18H32 O16.3H2O, M(r) = 558.48, is orthorhombic, P2(1)2(1)2(1) with a = 31.164(7), b = 13.111(5), c = 11.636(5) A, and Z = 8. The structure was solved by direct methods, and refined to R = 0.035 for 3926 observed reflections. The unit cell contains two independent molecules having a similar conformation. The conformation of the alpha-(1-->2) glycosidic linkage is similar to that observed in erlose monohydrate, whereas the conformation of the alpha-(1-->4) glycosidic linkage differs significantly. The molecule has no intramolecular hydrogen-bonds except for the minor components of three-center bonds, but indirect intramolecular hydrogen-bonds through the water molecules are formed. The hydrogen-bond system in the crystal structure consists of infinite and finite chains crosslinked by water molecules.
Carbohydrate Conformation↗
Antithrombin and thrombolytic effects of a new antithrombin agent: angioscopic and angiographic comparison with heparin or batroxobin.
The antithrombotic effect of three different types of antithrombotic agents (antithrombin:argatroban, heparin, defibrinogenating agent:batroxobin) were evaluated in canine coronary and iliac arteries. An occlusive thrombus was produced by balloon injury. One of the three agents was infused intravenously at 1 hour after thrombus formation (heparin 250 U/kg, argatroban 0.5 mg/kg, batroxobin 0.5 U/kg) and the effect of thrombus size reduction was evaluated. On the contralateral side of the iliac artery, the preventive effect of these agents on thrombus formation was evaluated after balloon injury. In the iliac artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 69% to 32% in the argatroban group, and from 64% to 51% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography demonstrated the same trend. The percent area stenosis with thrombus at 60 minutes following balloon injury was 0.75% in the argatroban group, 18.9% in the heparin group (P < 0.05 vs argatroban), and 12.9% in the batroxobin group. Thrombus size at the treated site was smaller than that at the control site in all three groups (P < 0.05 vs control). In the coronary artery, angioscopic percent area obstruction by the thrombus before and 60 minutes after treatment reduced from 84% to 53% in the argatroban group, and from 86% to 68% in the batroxobin group (P < 0.0001 and P < 0.05, respectively). No significant change was observed in the heparin group. Angiography also demonstrated the same trend. The activated partial thromboplastin time (APTT) was prolonged to 189% of the control value with argatroban and to 1253% of the value with heparin (P < 0.0001). Fibrinogen was markedly reduced with batroxobin. These results showed that both the antithrombin agent and the defibrinogenating agent have a preventive effect on thrombus formation and the effect on thrombus size reduction, without marked prolongation of the APTT.
Angiography↗
[MECHOP-BM chemotherapy in the treatment of non Hodgkin's lymphoma].
Twenty patients with previously untreated advanced aggressive or relapsed or refractory non-Hodgkin's lymphoma were treated with the MECHOP-BM regimen (MCNU, etoposide, cyclophosphamide, adriamycin, vincristine, prednisolone, bleomycin and methotrexate). Of the 18 patients treated with the MECHOP-BM, the response rate was 78% and complete response (CR) was attained in 33%. Among these CR patients, one patient relapsed, but the other patients continued to show CR (59-243 days, medium 178 days). The most serious toxicity attributed to MECHOP-BM therapy was leukopenia. The mean white blood cell count dropped to 1,300/microliters, and only therapy could be useful in the treatment for patients with untreated aggressive and advanced stage of non-Hodgkin's lymphoma as well as salvage therapy of relapsed cases.
Adolescent↗
Characteristics of lysophospholipase activity expressed by cytosolic phospholipase A2.
Evidence has accumulated to suggest that a wide variety of mammalian cells and tissues express a cytosolic phospholipase A2 with arachidonoyl preference (cPLA2). Purified rabbit platelet-derived cPLA2, as well as the human recombinant enzyme originally identified in the monocytic leukemic cell line U937, exhibit significant lysophospholipase activity. Several series of experiments indicated that a single protein mediated both activities. Treatment of the purified enzyme with p-bromophenacylbromide or an anti-(rabbit platelet cPLA2) monoclonal antibody, RHY-5, suppressed the activity of phospholipase A2 without any appreciable effect on lysophospholipase activity, suggesting that the domain(s) required for phospholipase A2 activity may be located separately from that for lysophospholipase activity. Lysophospholipase activity was appreciably detected above the critical micellar concentration of the substrate. Lysophosphatidylcholine was also hydrolyzed efficiently when it was incorporated into liposomes made of dialkylphosphatidylcholine. The hydrolysis of lysophospholipid was dependent on the fatty acid bound at the sn1 position; the relative rates of hydrolysis of 1-oleoyllysophosphatidylcholine, 1-palmitoyllysophosphatidylcholine, and 1-stearoyllysophosphatidylcholine were 23, 8, and 1, respectively. A similar order of reactivity was observed with lysophospholipid incorporated into dialkylphosphatidylcholine liposomes. cPLA2 may function not only as an arachidonate liberation enzyme but also as an enzyme responsible for degradation of certain molecular species of lysophospholipids formed in membranes.
Animals↗
The crystal and molecular structure of beta-D-fructofuranosyl alpha-D-xylopyranoside hemihydrate.
The crystal and molecular structure of beta-D-fructofuranosyl alpha-D-xylopyranoside (xylosucrose) hemihydrate, C11H20O10.0.5H2O, is orthorhombic, P2(1)2(1)2, with a = 20.919(5), b = 18.727(2), c = 7.071(1) A, V = 2770.1(2) A3, Z = 8, and Dx = 1.541 g.cm-3. The structure was solved by direct methods and refined to R = 0.040 for 2564 observed reflections. Two independent xylosucrose molecules exist in the unit cell, and their conformations about the 1-->2' glycosidic bond are similar to sucrose. The orientations of the primary hydroxyl groups in the two molecules differ. An O-1'...O-2 intramolecular hydrogen bond was observed in the one molecule, while an O-6'...O-5 intramolecular hydrogen bond was observed in the other involving disorder of O-6'.
Carbohydrate Sequence↗
The crystal and molecular structure of the trisaccharide erlose as the monohydrate.
Erlose [O-beta-D-fructofuranosyl-(1-->2)-O-alpha-D-glucopyranosyl-(1-->4)- alpha-D-glucopyranoside] monohydrate, C18H32O16.H2O, M(r) = 522.45, is orthorhombic, P2(1)2(1)2(1) with a = 30.748 (3), b = 8.757 (1), c = 8.270 (1) A, and Z = 4. The structure was solved by direct methods, and refined to R = 0.048 for 1909 observed reflections. The torsion angles about the (1-->2) and (1-->4) glycosidic bonds are similar to those observed in other sucrose- and maltose-like oligosaccharides. The maltose moiety has an O-3'-H...O-2 intramolecular hydrogen-bond, but the sucrose moiety has no intramolecular hydrogen bonds. The hydrogen bonding in the crystal includes infinite and finite chains crosslinked by the water molecule.
Carbohydrate Conformation↗
Effects of a highly selective plasma kallikrein inhibitor on collagen-induced arthritis in mice.
A study was conducted to evaluate the effects of a new, highly selective plasma kallikrein inhibitor, PKSI-527, on collagen-induced arthritis (CIA) in mice. PKSI-527 or indomethacin was administered daily intraperitoneally from day 20 postimmunization. Clinical evaluation was performed, and two of the components of the kallikrein-kinin system, high-molecular-weight (HMW) kininogen and plasma prekallikrein, were assayed. PKSI-527, as well as indomethacin, reduced the severity of arthritis significantly. PKSI-527, but not indomethacin, restored consumed components of the kallikrein-kinin system. These results suggest that PKSI-527 suppresses CIA by modifying the kallikrein-kinin system and PKSI-527 as a synthetic plasma kallikrein inhibitor would be a valuable tool to study the mechanism of inflammation of arthritic diseases.
Animals↗
Reduction of thrombogenicity with argon laser angioplasty. Comparison with balloon angioplasty.
Direct argon or thermal laser angioplasty (LA) was evaluated for thrombogenicity using angioscopy, and compared with balloon angioplasty (BA). In each of 8 dogs, 4 segments (both proximal and distal iliac arteries) were treated by laser-thermal and/or balloon angioplasty. One segment was treated by balloon angioplasty and 3 other segments were treated with either thermal LA with 7 W using a "Hot-Tip" laser probe (2.0 mm), or BA and thermal LA, or a special optical probe which emits a 3 W argon laser beam. Mean percent area stenosis by thrombus was 44 +/- 23 in balloon-dilated, 23 +/- 21 in thermally-treated and balloon-dilated, 3 +/- 3 in thermally-treated, and 1 +/- 4 in directly-lased segments at 30 min. It was 62 +/- 28 in balloon dilated, 31 +/- 29 in thermally-treated and balloon-dilated, 5 +/- 6 in thermally-treated, and 1 +/- 2 in directly-lased segments at 60 min. Balloon-inflated segments had the highest percent area stenosis which was significantly higher than that of either the direct laser or thermally-treated segments (p < 0.0005). Histology showed thermal necrosis in laser-treated sites, and wall tears in BA sites. Thus, LA can provide a less thrombogenic arterial surface than BA.
Angioplasty, Balloon↗
[Angioscopic evaluation of atherosclerosis].
Recently, percutaneous transluminal angioscopy has been clinically used. We describe the evaluation of atherosclerosis by angioscopy. In observation of aortic and peripheral arteries, color of the luminal surface is yellow in the lesion without endothelial fibrosis, whereas, it is white with endothelial fibrosis. A variety of findings such as endothelial flap, endothelial thickening, mural bleeding, mural or occlusive thrombi are observed in the atherosclerotic lesions. It is difficult to detect these findings by angiography. In observation of coronary arteries, color of the luminal surface is yellow or white and often associates spiral folds in the early stage of atherosclerosis. Plaques are classified to two categories. One is the complex plaque characterised by endothelial flap, rupture of atheroma, ulceration, mural thrombus and usually observed in patients with unstable angina or myocardial infarction. Another is the regular plaque without those findings and observed in patients with stable angina. Angioscopy is useful for evaluation of atherosclerosis.
Angioscopes↗
Heterotopic bone formation induced by bone morphogenetic protein in mice with collagen-induced arthritis.
A study was conducted to investigate the influence of systemic inflammation on heterotopic bone formation induced by bone morphogenetic protein (BMP). Five-milligram pellets of BMP were implanted in mice with type II collagen-induced arthritis. Intraperitoneal injections of interleukin-1 (IL-1) were also administered to a group of mice without collagen-induced arthritis. The amount of BMP-induced heterotopic bone formation was evaluated by soft X-ray radiography, histology, and assay of calcium content. BMP-induced heterotopic bone formation was markedly enhanced in mice with collagen-induced arthritis, and also in IL-1-treated mice. These findings suggest that bone formation is enhanced in mice with collagen-induced arthritis, and that IL-1 may be responsible.
Animals↗
Caroli's disease in three siblings.
Three sisters with cystic dilatation of the intrahepatic bile ducts (Caroli's disease) are reported. The index case, a 41-year-old woman with remittent high fever and right upper quadrant abdominal pain, was diagnosed as Caroli's disease with hepatic lithiasis and cholangitis based on findings of ultrasonography, computed tomography and endoscopic retrograde cholangiography. Her two older sisters were also examined and found to have the same disease without clinical symptoms. Their symptoms, locations of the dilated ducts and complications all varied. The hereditary mode of Caroli's disease in 13 families (32 cases) reported in the world literature including our study was examined. While Caroli's disease is thought to be an autosomal recessive disease, a conclusion on the hereditary mode of transmission could not be made in this study because of an insufficient investigation of family members, especially the parents.
Adult↗
Telescience testbed examination aboard Japanese Experiment Module (JEM): life and material science experiments.
A telescience ground testbed experiment was conducted by the National Space Development Agency of Japan (NASDA) at the Tsukuba Space Center in March 1991. The objectives of the ground testbed experiment were to extract scientists' requirements for a communication method, to evaluate the influence of transmission delay and capacity on experiment operations, and to evaluate performance and functions of the system for the testbed experiment. The microscopic operations experiment, the image furnace experiment and the onboard training experiment were selected as typical ground testbed experiments. In these experiments, motion video transmission at 320 kbps was acceptable for observing the experiments and communicating between the principal investigator and the payload specialist. In the microscopic operations experiment, motion video transmission at 1.5 Mbps or more was required for detailed observation. A 4-second transmission delay (roundtrip) was allowable for mutual communication.
Aerospace Medicine↗
Immunochemical detection of arachidonoyl-preferential phospholipase A2.
Monoclonal antibodies were raised against rabbit platelet cytosolic arachidonoyl-preferential phospholipase A2. The antibodies precipitated the arachidonoyl-preferential phospholipase A2 activity in the soluble fraction of a rabbit platelet lysate in combination with an immobilized anti-mouse immunoglobulin antibody, and reacted predominantly with a protein exhibiting a molecular weight of approximately 88,000 on immunoblotting analysis. All three antibodies established so far reacted with human platelet arachidonoyl-preferential phospholipase A2 as effectively as the rabbit platelet enzyme. One of them reacted with the rat platelet arachidonoyl-preferential enzyme, whereas none of them reacted with rabbit platelet secretory 14-kDa group II phospholipase A2. The existence of an immunologically related phospholipase A2 was further shown in rabbit granulocytes, brain, lung, and liver, rat and mouse mast cells, and human monocytoma U937 cells. Thus, an arachidonoyl-preferential phospholipase A2 with similar structural properties appeared to be expressed in a variety of cells and tissues.
Animals↗
Detection of three distinct phospholipases A2 in cultured mast cells.
Phospholipase A2 activity in lysates of mast cells such as rat mastocytoma RBL-2H3 cells and mouse bone marrow-derived IL-3-dependent mast cells (BMMC) was measured using phosphatidylcholine (PC), phosphatidylethanolamine (PE), or phosphatidylserine (PS) as a substrate. Both types of cells exhibited phospholipase A2 activity with a similar pH profile; the optimum pH observed with PS as a substrate was 5.5-7.4, whereas that with PE or PC was 8.0-9.0. PE and PC bearing an arachidonate at the sn-2 position were cleaved more efficiently by PE, PC-hydrolyzing phospholipase A2 than phospholipids with a linoleate. A monoclonal antibody raised against rabbit platelet 85-kDa cytosolic phospholipase A2 absorbed the PE, PC-hydrolyzing activity. PS-hydrolyzing activity was purified from RBL-2H3 cells and BMMC by sequential heparin-Sepharose, butyl-Toyo-pearl, and reverse-phase HPLC. On reverse-phase HPLC, the PS-hydrolyzing activity of RBL cells was separated into two peaks, A and B. The peak B activity was inhibited by the anti-rat 14-kDa group II phospholipase A2 antibody, while the peak A activity was not. The partially purified peak A activity hydrolyzed PS about 10-fold more efficiently than PE at optimum pH of 5.5-7.4. No appreciable hydrolysis was observed with PC or phosphatidylinositol (PI). Thus, mast cells may express at least three distinct phospholipases A2; 14-kDa group II phospholipase A2, 85-kDa cytosolic arachidonate preferential phospholipase A2, and a novel phospholipase A2 that shows high substrate specificity for PS.
Animals↗