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Biomedical subjects

Y Ikegami

Publications and source records attributed to Y Ikegami.

At least 73 records · Page 4Linked to original sources
PubMed1990

Topostin, a novel inhibitor of mammalian DNA topoisomerase I from Flexibacter topostinus sp. nov. I. Taxonomy, and fermentation of producing strain.

We found a new inhibitor of mammalian DNA topoisomerase I, named topostin, from a bacterial culture. The bacteria was identified as Flexibacter topostinus sp. nov., B-572. Morphological and physiological characteristics, and utilization of sugars were examined. Comparison of the strain with known species of the genus Flexibacter was made and indicates that the strain is a new species of the genus Flexibacter. The bacteria produced the inhibitor in parallel with their growth up to 72 hours.

Culture Media↗
PubMed1990

Topostin, a novel inhibitor of mammalian DNA topoisomerase I from Flexibacter topostinus sp. nov. II. Purification and some properties of topostin.

We describe the isolation of inhibitors of mammalian DNA topoisomerase I, named topostins, from a culture broth of Flexibacter topostinus sp. nov. and some properties of the inhibitors. Topostins A1, A2 and B were isolated by differential solubility in solvents, adsorption chromatography on silica gel and gel filtration on a Sephadex LH-20 column. Topostins A1, A2 and B had specific activities of 4,700, 16,000 and 22,000 U/mg, respectively. The most active metabolite topostin B comprised two components with MW of 567 and 553 in an equimolar ratio.

Chromatography, Affinity↗
PubMed1990

[A case of pulmonary nocardiosis diagnosed by percutaneous aspiration].

A 71-year-old man complained of mild dyspnea, and his chest X-ray showed a cavitating lesion accompanied by infiltrative changes in the right middle lobe. Percutaneous aspiration revealed numerous gram-positive and acid-fast branching rods. Morphological examination and biochemical tests of the colonies confirmed the diagnosis of pulmonary nocardiosis caused by nocardia asteroides. The patient was treated successfully with sulfamethoxazole-trimethoprim. It has been reported that approximately half of the patients with pulmonary nocardiosis have immunodeficiency, but our patient had no underlying disease. This disease has no characteristic clinical features, so diagnosis is difficult. As nocardia may involve the central nervous system leading to a poor prognosis, early diagnosis and prompt treatment are required to improve survival.

Aged↗
PubMed1989

Persistence and expression of circular DNAs encoding Drosophila amylase, bacterial chloramphenicol acetyltransferase, and others in Xenopus laevis embryos.

We injected circular forms of several different DNAs into fertilized eggs of Xenopus laevis, and studied the persistence and expression of the injected DNAs during early embryonic development. When we injected plasmids which contained Drosophila amylase genes, the copy number of the injected DNA increased only slightly during cleavage, started to decrease at the blastula stage, then became very small at the tadpole stage. In such embryos, Drosophila amylase activity was detected at and after the gastrula stage. When we injected other kinds of circular DNAs (pX1r101A, cDm2055, pII25.1, pBR322, and pSP-64-L14), their copy number did not increase throughout the early stages. When circular plasmids that contained bacterial chloramphenicol acetyltransferase (CAT) genes were injected, their copy number usually did not increase, but sometimes, for unknown reasons, it increased extensively throughout the blastula to gastrula stages. In both cases, CAT enzyme activity started to be expressed during the blastula to gastrula stages and disappeared at the 2 day-old tadpole stage. The level of CAT enzyme activity was roughly proportional to the amount of CAT mRNA formed, and also to the copy number of injected genes. From these results, we concluded that in Xenopus embryos, exogenously-injected circular DNAs are preserved for the most part as circular DNAs, and that the increase in their copy number within the embryos is not prerequisite for the expression of their genetic information.

Amylases↗
PubMed1988

Mechanism of O2- generation in reduction and oxidation cycle of ubiquinones in a model of mitochondrial electron transport systems.

O2- generation in mitochondrial electron transport systems, especially the NADPH-coenzyme Q10 oxidoreductase system, was examined using a model system, NADPH-coenzyme Q1-NADPH-dependent cytochrome P-450 reductase. One electron reduction of coenzyme Q1 produces coenzyme Q1-. and O2- during enzyme-catalyzed reduction and O2+ coenzyme Q1-. are in equilibrium with O2- + coenzyme Q1 in the presence of enough O2. The coenzyme Q1-. produced can be completely eliminated by superoxide dismutase, identical to bound coenzyme Q10 radical produced in a succinate/fumarate couple-KCN-submitochondrial system in the presence of O2. Superoxide dismutase promotes electron transfer from reduced enzyme to coenzyme Q1 by the rapid dismutation of O2- generated, thereby preventing the reduction of coenzyme Q1 by O2-. The enzymatic reduction of coenzyme Q1 to coenzyme Q1H2 via coenzyme Q1-. is smoothly achieved under anaerobic conditions. The rate of coenzyme Q1H2 autoxidation is extremely slow, i.e., second-order constant for [O2][coenzyme Q1H2] = 1.5 M-1.s-1 at 258 microM O2, pH 7.5 and 25 degrees C.

Anaerobiosis↗
PubMed1988

Properties of a coenzyme, pyrroloquinoline quinone: generation of an active oxygen species during a reduction-oxidation cycle in the presence of NAD(P)H and O2.

The oxidation of NAD(P)H by pyrroloquinoline quinone (PQQ) was non-enzymatically carried out at physiological pH in the presence of O2. The PQQ-NAD(P)H system requires about 1 mol of O2 for the oxidation of 1 mol of NAD(P)H. The oxidation of NAD(P)H occurred at a pseudo-first-order rate with respect to NAD(P)H and was of zero order with respect to PQQ concentration in in the presence of O2: k0[PQQ] [NAD(P)H] = k1 [NAD(P)H], where k0[PQQ] = k1, in which [PQQ] represents the initial concentration of PQQ. k0 values for NADH and NADPH were 3.4.10(2) M-1.min-1 and 2.0.10(2) M-1.min-1, respectively, at 25 degrees C and at 258 microM O2 (initial concentration). The system produced O-2, probably by the interaction of PQQ.H and/or NAD(P).with O2, during the oxidation of NAD(P)H. PQQH2 and PQQ.H were easily oxidized to PQQ in the presence of O2, yielding H2O2.

Coenzymes↗
PubMed1988

[Serum thyrotropin concentrations in patients with Sheehan's syndrome: reevaluation of the usefulness in the diagnosis].

Serum concentrations of thyroid-stimulating hormone (TSH) were determined, using a highly sensitive immunoradiometric assay (IRMA), in 10 patients with Sheehan's syndrome. Serum TSH levels in these patients were from 2.3 to 9.0 microU/ml, with the mean of 6.4 +/- 2.3(SD) microU/ml, and the data were similar to those measured by a conventional RIA method. The levels of serum TSH in these patients were normal or even higher than those of healthy women (1.8 +/- 1.3 microU/ml). After supplement therapy by cortisol, serum TSH levels decreased, but remained within the detectable range that was greater than 0.15 microU/ml. After supplement therapy by 1-thyroxine (T4), serum TSH levels moderately decreased in all patients, and excessive 1-T4 administration resulted in a fall of serum TSH levels to lower than the detectable limit. Thyroidal 123 I uptake was low in 3 out of 6 patients examined, which supports a recent hypothesis of reduced biological activity of the patient's TSH. While, the remaining 3 patients had normal thyroidal 123 I uptake, and administration of perchlorate had no effects on thyroidal radioactivity. Thus, it may be possible that in the former group of patients the TSH has a reduced biological activity, and in the latter group of patients, iodine trapping is intact but further synthesis and secretion of thyroid hormone from the gland are impaired. When the response of serum TSH to TRH was examined, the peak serum TSH levels increased in all patients. The peak TSH levels were 4.8 to 10.2 microU/ml with the mean of 7.5 microU/ml, but the data overlapped with those of normal subjects (peak level ranging 5.9 approximately 27.7 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Development of a telemetry system for measuring oxygen uptake during sports activities.

A new system for continuous measurement of oxygen uptake by means of a telemeter has been developed. Oxygen uptake and pulmonary ventilation during rest and exercise were determined using a portable oxygen consumption meter (Oxylog). A small interface circuit between the Oxylog and the transmitter of a frequency modulated bio-telemeter system was designed and installed inside the Oxylog. Data from the transmitter were passed to a receiver and were fed into a microcomputer system. The microcomputer system displayed and printed out minute values of ventilation and oxygen uptake. The accuracy and reliability of the new system were checked by comparison with the traditional (Douglas bag) method. In the range less than 80 l.min-1 of ventilation and less than 2 l.min-1 of oxygen uptake, the system was not inferior to the Douglas bag method. The new system was applied for field continuous measurement of oxygen uptake during a doubles tennis game. The results of the application indicate that the telemetry system developed here is a very practical and useful way of measuring oxygen uptake during sports activities.

Adult↗
PubMed1988

Development of hyperthyroidism following primary hypothyroidism: a case report with changes in thyroid-related antibodies.

We report a 48-year-old woman who developed hyperthyroidism following primary hypothyroidism. The serum T4 level was initially low and serum TSH level was high with clinical signs of hypothyroidism. The thyroid gland was not enlarged. Therapy with L-T4 was started. Three years later she developed hyperthyroidism; serum free T4 increased to 29.1 pmol/l after cessation of L-T4 therapy. The 123I thyroid uptake was increased with no suppression by exogenous T3. When she was hypothyroid, the activity of thyroid stimulating antibodies (TSAb) in serum measured by cyclic AMP production in cultured porcine thyroid cells were negative at 93.4% (normal less than 140%), while thyroid stimulation-blocking antibodies (TSBAb) determined by inhibition of TSH-induced cyclic AMP increase were positive at 96.1% (normal less than 40%). When hyperthyroidism subsequently occurred, TSBAb became negative (30.9%), while TSBAb became positive (163.3%). The findings indicate that hypothyroidism due to the potent TSBAb activity is not always persistent, but can be changed when various types of thyroid-relating antibodies change in the course of the disease.

Antibodies↗
PubMed1987

Characterization of a mammalian mutant with a camptothecin-resistant DNA topoisomerase I.

DNA topoisomerase I was purified to near homogeneity from a clonal line of human lymphoblastic leukemia cells, RPMI 8402, that is resistant to camptothecin, a cytotoxic alkaloid from Camptotheca acuminata, and compared with that of the parent wild-type cells. As assayed by relaxation of the supercoiled plasmid DNA and by formation of enzyme-linked DNA breaks, the purified enzyme from the resistant cells was shown to be greater than 125-fold as resistant to camptothecin as the wild-type enzyme, comparable to a cellular resistance index of about 300. Therefore, the cellular resistance appears to be due to the resistance of the enzyme. The amount of the immunoreactive enzyme protein in whole extract appeared to be reduced to less than half that of the wild-type enzyme. These results establish that DNA topoisomerase I is the cellular target of camptothecin and that DNA topoisomerase I is essential for the survival of mammalian cells.

Camptothecin↗
PubMed1987

ESR studies on the active intermediate in the enzymatic reduction of the Fe-bleomycin complex.

The spin trapping method was applied to elucidate the active intermediate during the enzymatic reduction of Fe(III)-bleomycin in the presence of NADPH-cytochrome P-450 reductase and O2. Although the hydroxyl adducts to spin traps were observed, the adduct formation was not inhibited by catalase nor by SOD. Furthermore, in Tris-HCl buffer, no Tris adduct to the spin trap was observed. The results lead to the conclusion that there is no participation of free OH radical in the reactive intermediate in this reduction system. Effect of phosphate buffer on the reactivity of Fe(II)-bleomycin and spin state of Fe(III)-bleomycin were discussed.

Animals↗