Studies on the biosynthesis of fosfomycin. 4. The biosynthetic origin of the methyl group of fosfomycin.
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Fosfomycin↗
Biomedical subjects
S Imai
Publications and source records attributed to S Imai.
Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme.
An enzymatic activity catalyzing P-methylation of N-acetyldemethylphosphinothricin, a biosynthetic intermediate of the herbicide bialaphos, was detected in a cell extract of Streptomyces hygroscopicus SF-1293, a bialaphos producing organism. The gene coding for this P-methylation enzyme in the bialaphos biosynthetic gene cluster was also expressed in Streptomyces lividans. The methyl donor of the reaction was determined to be methylcobalamin. The P-methylation enzyme utilized both N-acetyldemethylbialaphos and N-acetyldemethylphosphinothricin as substrates.
Herbicides↗
Adipostatins A and B, new inhibitors of glycerol-3-phosphate dehydrogenase.
As a result of screening for inhibitors of glycerol-3-phosphate dehydrogenase, which may be effective to prevent corpulence, we isolated two inhibitors named adipostatin A and adipostatin B from the culture broth of Streptomyces cyaneus 2299-SV1. Their structures have been established to be 5-n-pentadecylresorcinol and 5-isopentadecylresorcinol, respectively. Adipostatin A and adipostatin B inhibited glycerol-3-phosphate dehydrogenase at the IC50 values of 4.1 microM and 4.5 microM, respectively. These compounds prevented triglyceride accumulation in 3T3-L1 cells at a concentration of the microM level.
3T3 Cells↗
[Echocardiographic assessment of cardiac function in the children of chronic renal failure with cardiomegary].
Five children (four boys and one girl) with chronic renal failure (CRF) developed congestive heart failure 0.5 to 11 years after the onset of the disease. Their ages were from 4 to 13 years old. They noticed tachypnea, tachycardia, cough, chest anxiety, general fatigue and their chest X-rays showed cardiomegaly with cardio-thoracic ratio (CTR) of from 55 to 63% and pulmonary congestion. Their echocardiograms showed no cardiomuscular hypertrophy, but the dilatation of left ventricular diastolic diameter (LVDd), and the decreased ejection fraction (EF) were observed. They were treated with water restriction, antihypertensive agents, cardiotonics and dialysis. Their clinical symptoms improved promptly, but their cardiomegary and echocardiographic findings improved gradually. The causes of heart failure in these patients seemed to be due to uremia, fluid overload and hypertension. The echocardiographic examination was useful for the management of the children with CRF in heart failure.
Adolescent↗
[Effect of proton pump inhibitor, in combination with epidermal growth factor, on the healing of chronic gastric ulcer in submandibular gland removed rats].
The effect of a proton pump inhibitor, omeprazole (OPZ), in combination with mouse epidermal growth factor (EGF), on the healing of chronic gastric ulcers induced by acetic acid in submandibular glands removed rats (SMR rat) was investigated. Four separate groups of SMR rats were orally administered 1 ml of distilled water (control), 100 mg/kg of OPZ alone (OPZ), 5 micrograms/kg of mouse EGF alone (EGF), or combination with (EGF + OPZ) twice daily. Two weeks later, ulcer areas of four groups were measured and expressed as the ulcer index (UI). The UI of the OPZ and EGF + OPZ group was significantly reduced as compared with that of the control. Furthermore, the UI of the EGF + OPZ group was significantly smaller than that of the EGF group. The present study indicates that the proton pump inhibitor promotes healing of chronic gastric ulcers in SMR rats and the effect of the proton pump inhibitor is enhanced by administration of mouse EGF.
Acetates↗
[Antiproliferative actions of medroxyprogesterone acetate (MPA) to human ovarian cancer cell lines in vitro].
The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA-added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma, Mucinous↗
[Epstein-Barr virus (EBV): detection of EBV genomic sequences by polymerase chain reaction (PCR)].
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Genome, Viral↗
[Expression of c-erbB-2 protein and vessel invasion in colorectal cancer].
Using sections of formalin-fixed, paraffin-embedded tissues from 64 colorectal cancer patients, the expression of c-erbB-2 oncoprotein was studied immunohistochemically. Twenty-seven percent of the cases with liver metastasis showed positive staining. On the other hand, only 3% of cases without liver metastasis were positive. Expression rates of c-erbB-2 protein in liver metastasis cases showed no significant difference between primary operation (26%) and recurrence (27%). Of all c-erbB-2 positive patients, 90% (9/10) had liver metastasis. Secondly, vessel invasions of 45 rectal cancer patients were studied using Victoria Blue (VB) elastic staining and endothelial staining by factor VIII-related antigen and Ulex europaeus agglutinin I (UEA-I) lectin. VB-HE double stain was efficacious to detect vascular invasion, but endothelial staining was not. There were statistically more vascular invasions in 30 patients with liver or lymph node metastases than in those without metastasis. And in cases with metastasis, many vascular invasions into the extra-muscular layer were seen. Both vascular invasions and c-erbB-2 protein were valuable indicators of possible liver metastasis.
Biomarkers, Tumor↗
[Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].
We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Involvement of charybdotoxin-sensitive K+ channel in the relaxation of bovine tracheal smooth muscle by glyceryl trinitrate and sodium nitroprusside.
To elucidate the involvement of K+ channels in the smooth muscle relaxation by glyceryl trinitrate (GTN) and sodium nitroprusside (SNP), effects of several K+ channel antagonists on the relaxant responses to GTN, SNP and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) were studied in bovine tracheal smooth muscle. Although an antagonist of large conductance Ca(++)-activated K+ channel, charybdotoxin, produced no definite effect on the relaxation induced by GTN, SNP and atriopeptin in the rabbit aortic ring preparation, this antagonist inhibited the relaxation by GTN, SNP, atriopeptin and 8-Br-cGMP in the bovine tracheal smooth muscle. Methylene blue, a soluble guanylate cyclase inhibitor, also had an inhibitory effect on the relaxation by GTN and SNP. Both apamin, a small conductance Ca(++)-activated K+ channel antagonist, and glibenclamide, an ATP-sensitive K+ channel antagonist, did not exhibit any inhibitory effect on the relaxant responses to GTN and SNP. GTN and SNP increased cGMP content. The increment was attenuated by methylene blue, whereas it was unaffected by charybdotoxin. These results indicate the involvement of large conductance Ca(++)-activated K+ channel in the relaxation of bovine tracheal smooth muscle by GTN, SNP and 8-Br-cGMP. The activation of K+ channel by GTN and SNP is thought to occur via increases in cGMP content.
Animals↗
[Report of three cases of emergency surgical salvage for acute pulmonary embolism].
Pulmonary embolism (PE) is one of the increasing diseases in Japan, which is aggravated rapidly and early diagnosis is necessary to improve its prognosis. We experienced three cases of successful surgical salvage. It is emphasized that the Doppler ultrasonic echocardiography plays important part in diagnosing PE early and noninvasively. Namely, it shows a appearance of acute cor pulmonale, and is usually able to guess the pulmonary artery pressure by using the simplified formula of Bernoulli's equation. We believe that the surgical pulmonary embolectomy under the cardiopulmonary bypass should be immediately considered in case of unsatisfactory conservative thrombolytic therapy.
Acute Disease↗
[Evaluation of loco-regional cancer chemotherapy with assistance of home parenteral nutrition].
Out of 79 cases dealt with reservoir, a response was obtained in 31% of 51 assessable cases. When assessed by cumulative survival with Kaplan-Meier method, the 50% survival was 8 months for total cases and prolonged to 21 months for responsive cases. However, eventually re-hospitalization was required for almost all cases. Although oral nutrition was impossible because of poor general condition, there were many patients who refused re-hospitalization and wished to continue treatment at home. In the present study, in 5 such cases the usefulness of home parenteral nutrition (HPN) combined with chemotherapy was determined. All the five patients in this study had gastric cancer with metastases and recurrent lesions in the liver or lymph node, or localized or with peritoneal spread. The site of the reservoir was within the artery in 4 cases and in the abdominal cavity in 1 case. The chemotherapy was multidrug-combination therapy consisting of 5-FU, MMC, CDDP and EPIR. In 4 cases local hyperthermia was added. In 3 out of the 5 cases (3 out of 7 lesions), a partial response (PR) was obtained. The mean dwelling period of the reservoir was 349.2 days for all cases, but longer than 400 days for 3 cases in which PR was obtained. For HPN, a catheter was inserted through the internal cervical vein, and 750-1,500 kcal/day was administered intermittently during night or constantly for 24 hours. In cases in which PR was obtained with chemotherapy and in those in which the reservoir for HPN was been in place before the terminal stage, the reservoir could be used for administration for a prolonged period. The mean dwelling period of the reservoir was 179.8 days and the duration of home stay was 121.2 days. All of the patients were classified as PS2 or higher and pronounced improvement in PS was obtained after HPN in only 1 case. Four out of the 5 patients were satisfied with receiving treatment at home. However, since HPN is associated with many problems such as sudden worsening in general condition, cancer pain and great burden to families, the solution to these problems remains.
Aged↗
[Results of modified LSA2-L2 protocol with moderate-dose MTX therapy in children with untreated non-Hodgkin's lymphoma].
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Adolescent↗
[A case of the emergency salvage from the thrombotic occlusion of the Fontan conduit in tricuspid atresia].
The thrombotic occlusion of the Fontan conduit is one of the most fatal complications after Fontan procedure. Its survival case by the successful emergency surgery is reported. A 17-year-old male who had undergone Fontan procedure three years before for tricuspid atresia, using the expanded PTFE graft of 19 mm in internal diameter, had several episodes of palpitation due to probable paroxysmal atrial fibrillation. He suddenly complained chest oppression feeling and suffered paroxysmal atrial tachycardia following after atrial fibrillation. The radionuclide angiocardiography was performed immediately, which revealed clearly that the Fontan conduit had occluded by the thromboembolism in spite of the prophylactic anticoagulant therapy. Then the emergency surgery was performed successfully, in which the occluded Fontan conduit was replaced with another expanded PTFE graft of 20 mm in internal diameter under the extracorporeal circulation. It seemed that the inducement of this thrombotic occlusion of the Fontan conduit was paroxysmal atrial fibrillation. We emphasize the importance of the prevention of arrhythmias in the postoperative care of the Fontan procedure. Additionally we do emphasize the usefulness of the radionuclide angiocardiography which is available and non-invasive. Especially, first-pass study is much informative to elucidate the circulatory states in the cardiac anomalies.
Adolescent↗
Effects of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine on platelet aggregation and thrombosis in experimental animals.
Antiplatelet and antithrombotic effects of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) were studied. KC-764 inhibited arachidonic acid (AA)- and collagen-induced platelet aggregation with IC50s of 1.0 x 10(-8)-2.8 x 10(-7) mol/l for humans, rabbits, guinea pigs and dogs, and IC50s of 3.9 x 10(-6)-3.7 x 10(-5) mol/l for mice and rats in vitro. KC-764 inhibited AA- and collagen-induced aggregation with ID50s of 0.04-0.09 mg/kg p.o. in rabbits and dogs, and ID50 of 13.0 mg/kg p.o. in rats. These antiaggregatory activities of KC-764 were stronger than those of acetyl-salicylic acid (ASA), indometacin, cilostazol and ticlopidine. KC-764 inhibited the production of thromboxane B2 (TXB2) in rabbit platelet microsomes, washed platelets and reconstituted platelet rich plasma (RPRP) with IC50s of 2.9 x 10(-6) mol/l, 2.8 x 10(-7) mol/l and 4.3 x 10(-8) mol/l, respectively. The in vitro inhibitory activity of KC-764 on AA-induced platelet aggregation was more potent when RPRP was used rather than washed platelet suspension containing 30% rabbit plasma. ASA did not show such an augmentation. KC-764 prevented collagen- and AA-induced thrombosis at more than 1 mg/kg p.o. and more than 0.1 mg/kg i.v. in mice and rabbits. KC-764 showed the wider margin of dose between antiplatelet action and prolongation of bleeding time in rabbits than ASA and indometacin. These results indicated that KC-764 was a potent antithrombotic drug to prevent TXB2 production and less possible to induce untoward actions as compared with ASA or indometacin.
Adenosine Diphosphate↗
Hepatectomy accelerates the growth of transplanted liver tumor in mice.
To study the effect of hepatectomy on the growth of liver tumor, Shionogi Carcinoma 42, a mammary tumor, was transplanted into the liver of mice which had undergone 40% hepatectomy. The liver tumor and the number of pulmonary metastases in hepatectomized mice were significantly larger than those in nonhepatectomized mice. Responses to lectins and IL-2, subpopulations, and cytotoxicity to YAC-1 and P815 cells of splenocytes were assessed to evaluate immunological status. At the initial phase after hepatectomy and tumor transplantation into the remaining liver, NK activity transiently increased, and function of B and T cells, especially of helper T cells, decreased, while B-cell function recovered beyond normal levels in a later phase. These results suggest that liver may play an important immunological role and that the immunological modification after hepatectomy may be responsible for the accelerated growth of liver tumor. Accordingly, some adjuvant immunotherapy may be recommended for the prevention of recurrence after hepatectomy for liver tumor.
Alanine Transaminase↗
[A case of malignant pleural mesothelioma with osseous and cartilaginous formation].
A 85-year-old man was admitted to our unit on November 17, 1989 with bloody sputum and abnormal shadow on chest X-ray film. Chest X-ray and CT on admission showed a large tumor mass approximately 9 cm in diameter in the right middle and lower lung field. Microscopic examination of the needle biopsy specimen from the tumor revealed biphasic malignant pleural mesothelioma. After admission, thoracentesis was performed, because of rapidly increasing right-sided pleural effusion. One of the two trochar catheter was inadvertently inserted in the tumor. Tumor tissue obtained through the catheter showed malignant mesothelioma with osseous and cartilaginous formation. Only isolated reports by Goldstein and Yousem have reported osseous and catilaginous differentiation in malignant mesothelioma. To our knowledge, this is the first reported case in Japan.
Aged↗
[Chromosome and DNA analyses of peripheral blood lymphocyte from the quadruple cancer patient].
The patient with quadruple cancer was a 32 year-old female who had osteosarcoma, bilateral breast cancer and adenocarcinoma of the lung. When chromosomal analysis of peripheral blood lymphocyte was performed, two abnormal cells were detected among 42 cells examined. The first cell showed a translocation involving chromosome 1 and 20 and trisomic for chromosome 19. The second cell was trisomic for chromosome x. Southern blot analysis of DNA from peripheral blood lymphocyte revealed that there was no difference in the expression of Rb gene between the patient and healthy adult.
Adenocarcinoma, Papillary↗