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Biomedical subjects

E Takagi

Publications and source records attributed to E Takagi.

At least 19 recordsLinked to original sources

Preparation of platinum nanoparticles by sonochemical reduction of the Pt(IV) ions: role of surfactants.

Sonochemical reduction processes of Pt(IV) ions in water have been investigated in the presence of various kinds of surfactants such as sodium dodecylsulfate (SDS) and sodium dodecylbenzenesulfonate (DBS) as anionic surfactants, and polyethylene glycol monostearate (PEG-MS) as non-ionic, dodecyltrimethylammonium chloride (DTAC) and bromide (DTAB) as cationic surfactants. An improved colorimetric determination reveals that Pt(IV) ion is reduced to zero valent metal in two steps: step (1)--Pt(IV) ion to Pt(II) ion, and step (2)--Pt(II) ion to Pt(0), and after the completion of step (1), step (2) sets in. It appears that rapid scrambling reactions among platinum ions and/or atoms, that is, Pt(I) + Pt(IV)-->Pt(II) + Pt(III), etc. take place. In the sonolysis of aqueous solutions of SDS, DBS or PEG-MS, two kinds of organic reducing radicals, R(ab) and R(py), are proposed to contribute to the reduction. Radical R(ab) is formed from the reaction of the surfactants with primary radicals such as hydroxyl radicals and hydrogen atoms originated from the sonolysis of water, and radical R(py) is formed from the direct thermal decomposition of surfactants in the interfacial region between the collapsing cavities and the bulk water. R(ab) is effective for both the reduction steps, whereas R(py) is involved only in the reduction step (1). This fact coincides with the previous reported sonochemical reduction of Pt(II) ions. Hydrogen atoms themselves scarcely participate in the reduction. The average diameter (1.0 nm) of platinum particles prepared from the system of PEG-MS is smaller than those from the aqueous solution of anionic surfactant SDS (3.0 nm) and DBS (3.0 nm).

Journal Article↗

Prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the long-term prognosis of completely asymptomatic adult patients with hypertrophic cardiomyopathy (HC). Diagnosis of HC was suspected because of an abnormal electrocardiogram and/or cardiac murmur and confirmed by echocardiography and/or left ventricular angiography, and hemodynamic investigation. BACKGROUND: Hypertrophic cardiomyopathy shows marked heterogeneity in clinical expression and prognosis. The prognosis of asymptomatic patients with HC has not been fully defined. METHODS: Of 128 consecutive adult patients with HC, 58 asymptomatic patients (Group 1, mean age 42.8 years) and 70 symptomatic patients (Group 2, mean age 50.4 years) were studied to assess cardiac mortality. Mean follow-up periods were 11.0 years for Group 1 and 9.1 years for Group 2. RESULTS: At presentation, Group 1 patients were younger and had smaller left atrial dimensions than did Group 2 patients. The annual cardiac mortality rate and the rate for sudden death alone in Group 1 were significantly lower than in Group 2 (0.9% vs. 1.9%, p < 0.05, 0.1% vs. 1.4%, p < 0.05, respectively). Although about one-third of the survivors in Group 1 had cardiac symptoms at their most recent evaluation, only one patient died suddenly compared with eight in Group 2. The annual mortality rate due to heart failure was similar in each group. Only a syncopal episode was associated with both cardiac death and sudden death for both groups combined. CONCLUSIONS: The cardiac mortality rate for completely asymptomatic adult patients with HC was very low, significantly lower than that of symptomatic patients, and there was a disproportionately low incidence of sudden death.

Adult↗

Effects of aging on left ventricular relaxation in humans. Analysis of left ventricular isovolumic pressure decay.

BACKGROUND: Some experimental studies in animals have shown that myocardial relaxation is prolonged with aging. However, it is not known whether aging alters ventricular isovolumic relaxation in human subjects. METHODS AND RESULTS: We analyzed high-fidelity left ventricular pressures, measured by use of a catheter-tipped manometer, and biplane left ventriculograms in 55 normal subjects who underwent diagnostic cardiac catheterization but who were found to have normal cardiac anatomy and function. There were 38 men and 17 women, ranging in age from 20 to 77 years. Left ventricular isovolumic relaxation was assessed by the exponential time constants of isovolumic pressure decay with (Tb) and without (Tw) an asymptote pressure. Left ventricular volume, ejection fraction, and wall thickness or mass were calculated from left ventricular angiograms. Neither of the time constants of left ventricular relaxation correlated with age (Tb: r = .001 to .10, P = NS: Tw: r = .02 to .05, P = NS). Left ventricular systolic function (ie, ejection fraction and end-systolic volume index), heart rate, and left ventricular wall thickness or mass, which are major hemodynamic determinants of left ventricular relaxation, were not significantly affected by aging. The multivariate analysis of age and hemodynamic variables against the time constants of left ventricular relaxation also indicated that no significant relation was found between age and left ventricular relaxation. CONCLUSIONS: In the absence of coronary artery disease, systemic hypertension, left ventricular systolic dysfunction, or hypertrophy, left ventricular relaxation assessed by the time constant of isovolumic pressure decay remains essentially unchanged with normal adult aging, at least until the eighth decade.

Adult↗

Relationship between left ventricular diastolic function at rest and exercise capacity in patients who have suffered a previous myocardial infarction.

To assess whether left ventricular (LV) diastolic function is a determinant of exercise capacity in patients who have suffered a previous myocardial infarction (MI), we investigated the relationship between maximum exercise duration and resting LV diastolic function in 65 MI patients. Each patient underwent both a symptom-limited exercise test and LV biplane angiography with simultaneous high-fidelity pressure measurements. LV relaxation was assessed by the time constants (T1/e and T1/2) of isovolumic pressure decay, and LV diastolic distensibility was assessed by the LV end-diastolic volume (V) index-pressure (P) ratio. The time constants of relaxation did not correlate with maximum exercise capacity (r = -0.19 for T1/e, NS; r = - 0.17 for T1/2, NS). LV diastolic distensibility also did not correlate with exercise capacity (r = - 0.08, NS). These results suggest that the resting LV diastolic dysfunction is unlikely to be the principal cause of exercise intolerance in MI patients without congestive heart failure.

Adult↗

Growth inhibition of Ureaplasma urealyticum by the proton pump inhibitor lansoprazole: direct attribution to inhibition by lansoprazole of urease activity and urea-induced ATP synthesis in U. urealyticum.

The proton pump inhibitors (PPIs) omeprazole and lansoprazole and the acid-activated analog of lansoprazole AG-2000, which potently inhibit the urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), also inhibited the urease activities of cell-free extracts as well as intact cells of Ureaplasma urealyticum. The 50% inhibitory concentrations were between 1 and 25 microM. These compounds also inhibited the ATP synthesis induced by urea in ureaplasma cells. The 50% inhibitory concentrations for ATP synthesis were close to those for urease activity, but they were lower than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. In addition, one of the metabolites of lansoprazole found in human urine, M-VI, also inhibited ureaplasmal urease activity and the ATP synthesis induced by urea at almost the same concentrations as those of lansoprazole. The inhibition of PPIs against ureaplasma urease was very similar to those against H. pylori urease, suggesting that the inhibitory mechanism against these ureases was due to the blockage of the SH residues on the cysteine of the enzyme. Omeprazole, lansoprazole, AG-2000, and M-VI inhibited the growth of U. urealyticum. Since ureaplasma urease is thought to be involved in the pathogenicity of this organism in the urogenital tract, PPIs and their analogs may be useful as chemotherapeutic agents against diseases caused by U. urealyticum.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Inhibitory action of lansoprazole and its analogs against Helicobacter pylori: inhibition of growth is not related to inhibition of urease.

The proton pump inhibitors omeprazole and lansoprazole and its acid-activated derivative AG-2000, which are potent and specific inhibitors of urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), inhibited the growth of H. pylori. The growth was inhibited not only in urease-positive clinical isolates but also in their urease-negative derivatives which had no urease polypeptides. AG-1789, a derivative of lansoprazole with no inhibitory activity against H. pylori urease, also inhibited the growth of both strains even more strongly than the urease inhibitors lansoprazole and AG-2000. Furthermore, the antibacterial activity of omeprazole and lansoprazole was not affected by glutathione or dithiothreitol, which completely abolished the inhibitory activity of lansoprazole against H. pylori urease. These results indicated that the inhibitory action of these compounds against the growth of H. pylori was independent from the inhibitory action against urease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Therapeutic effects of moxibustion on delayed uterine involution in postpartum dairy cows.

Moxibustion on 12 specific points (Keiketsu in Japanese) was applied for treatment of delayed uterine involution in 16 cows that were diagnosed on the basis of rectal palpation and vaginoscopic examination 21 to 35 days after parturition. The treatment was continued for three consecutive days. Other 32 cows with the delayed uterine involution were either injected intramuscularly with 25 mg PGF2 alpha (17 cows) or infused in utero with 500 mg ampicillin (15 cows). The uterine involution following the treatment was monitored by rectal palpation and vaginoscopic examination. Milk samples were collected three times weekly and used for milk progesterone assay to monitor the ovarian function. No significant difference was observed in the uterine involution among the groups treated with moxibustion, PGF2 alpha or ampicillin. Percentages of cows with abnormal cervical mucus and bacterial isolation from cervical swab decreased remarkably in all groups during 4 weeks after treatment. Forty-six percent of cows with delayed uterine involution was diagnosed as having inactive ovaries. Percentage of cows that responded with ovulation and corpus luteum formation after moxibustion was 67 percent, slightly higher than those in cows treated with PGF2 alpha or ampicillin. Reproductive performance after the moxibustion was well-comparable to those after PGF2 alpha or ampicillin treatment. Result indicates that the moxibustion could be used as the alternative to PGF2 alpha and antibiotics for treating delayed uterine involution in cows.

Administration, Topical↗

[Coronary artery disease in diabetic patients].

Although it is well known that diabetics have high mortality rates due to ischemic heart disease (IHD), controversies still exist about the severity of coronary artery disease in diabetics compared to nondiabetics. We compared coronary arteriographies of 50 diabetics with IHD to those of 50 nondiabetics with IHD. In regard to coronary risk factors, incidence of obesity was significantly higher in diabetics. Incidence of hypertension, hypercholesteremia, hyperuricemia was higher, although not significant, in diabetics. Incidence of smoking was significantly higher in nondiabetics. The diabetic group showed a significantly higher incidence of patients with more than two or three diseased vessels, and a significantly higher number of diseased coronaries with more than 50% stenosis per patient compared to nondiabetics (5.6 +/- 3.7 vs 3.7 +/- 3.2). The distribution of diseased coronaries with more than 75% stenosis showed no difference between diabetics and nondiabetics. The incidence of coronary spasm was significantly lower in diabetics (12% vs 28%). The high incidence of multiple vessel disease in diabetics was thought to be due to other complicated coronary risk factors, especially hypertension and hypercholesteremia.

Aged↗

Human alveolar macrophages of anergic patients with lung cancer lack the responsiveness to recombinant interferon gamma.

We studied the effect of recombinant interferon gamma (rIFN-gamma) on the phagocytic and bactericidal actions in human alveolar macrophages (AM) of patients with pulmonary tuberculosis and lung cancer. Treatment with 100 or 1,000 U/ml of rIFN-gamma for 24 hours resulted in an increased percentage of AM ingesting bacillus Calmette-Guérin (BCG) and an increased number of ingested BCG in individual AM in tuberculin-positive patients with lung cancer and pulmonary tuberculosis. The rIFN-gamma treatment also showed increased killing activity of AM in tuberculin-positive patients. However, rIFN-gamma treatment of AM in tuberculin-negative anergic patients with lung cancer did not induce the increase of phagocytic and killing activities against BCG. These results suggest that responsiveness and activation of AM to rIFN-gamma are inhibited in the anergic environment.

Aged↗

Rapid purification and structural study of DNA topoisomerase I from human Burkitt lymphoma Raji cells.

We have developed a rapid purification method for DNA topoisomerase I from Raji cells, a human Burkitt lymphoma cell line, using ammonium sulfate fractionation followed by chromatography on a Mono S column (FPLC, Pharmacia). By this method, the enzyme could be purified to near homogeneity within one day. Electrophoresis on sodium dodecyl sulfate polyacrylamide gel revealed that the final preparation is mainly composed of a 100-kDa protein. The major enzyme activity sedimented through a glycerol density gradient at 5.7S, accompanied with a minor peak at 8.7S. The former may correspond to the monomer of the 100-kDa polypeptide, and the latter, to its dimeric form. The gel filtration study of the crude extract revealed an active molecular species of 200 kDa, in addition to 100 kDa, and lower molecular weight forms. These results suggest that DNA topoisomerase I is largely in monomeric form, but also has a minor population of the dimeric form.

Burkitt Lymphoma↗

[Simultaneously diagnosed triple primary neoplasms--a case report].

Reported is a case of 71-year-old man who had triple primary neoplasms that were diagnosed simultaneously on admission. He visited our hospital for examination of an abnormal mass shadow seen in the right lower lobe of his chest in a roentgenogram. That was determined as being a small cell lung cancer. We simultaneously detected that a moderately differentiated tubular gastric adenocarcinoma and an olfactory groove meningioma were overlapped as well. Attention must be paid to multiple primary neoplasms, since some of these malignancies are predicted to overlap and the percentage of overlapped neoplasms is increasing. Care must be taken to avoid mistaking an overlapped tumor for a metastatic one. In 1986, according to the Annuals of Pathological Autopsy Cases in Japan, 2196 cases that represented 9.4% of all malignancies had overlapped tumors and triple or more overlapped cases amounted to 225 a year. Malignancies in the digestive system, the respiratory system, the urinary tract and in the endocrine system seem to be greatly affected with multiple neoplasms.

Adenocarcinoma↗

Phospholipid modulates in vitro replication of autonomous replicating sequence from human cells.

A cloned plasmid, pmyc(H-K), containing sequences derived from human c-myc gene replicated in vitro in Raji nuclear extract in a semiconservative manner. Using this system, it was found that phosphatidylinositol and cardiolipin strongly inhibited the replication of pmyc(H-K) in vitro, whereas other phospholipids, i.e., phosphatidylserine, phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, and sphingomyelin, had no appreciable effect. The concentrations of phosphatidylinositol and cardiolipin producing 50% inhibition of the replication were 4.6 and 5.4 microM, respectively. Phosphatidylinositol and cardiolipin inhibited the relaxation of pmyc(H-K) supercoiled DNA, but showed little or weaker effects on DNA polymerase alpha and topoisomerase II in Raji nuclear extract. These results suggest that phosphatidylinositol and cardiolipin antagonize the replication of pmyc(H-K) in vitro, through, at least in part, the interaction with topoisomerase I.

DNA Replication↗

Establishment and characterization of resistant cells to etoposide (VP16) from a mouse breast cancer cell line, FM3A.

We established 4 cell lines resistant to VP16 from a mouse breast cancer cell line, FM3A. The IC50 values of all 4 resistant strains were approximately 2 micrograms/ml as measured by colony formation in soft agar; about 40 times higher than that of parent cell (0.05 microgram/ml). These cells showed a cross-resistance to VM26, a compound related to VP16, but not to a variety of other antitumor drugs including adriamycin, mitomycin C, cis-platinum, 5-fluorouracil, bleomycin, vincristine, 4-hydroperoxycyclophosphamide, methotrexate and cytosine arabinoside. Topoisomerase II, the putative target of VP16, was partially purified from cells, and was assayed using knotted P4 phage DNA as a substrate. However, no significant difference was observed between enzymes from resistant cells and from the parent cells in either activity per cell or sensitivity to VP16. On the other hand, the resistance of these cell lines to VP16 was greatly reduced by adding a calcium antagonist, verapamil, to the soft agar at a concentration as low as 5 microM, at which the viability of cells was hardly affected. A similar verapamil-induced reduction in the resistance of the cells to VM26 was also observed. These results suggest that the acquired resistance may be largely due to an altered membrane permeability to drugs, which may be overcome by verapamil, rather than to an altered topoisomerase II.

Animals↗

[Adriamycin, cyclophosphamide, vincristine and methotrexate combination chemotherapy of small cell lung cancer].

Twenty-two patients who had not received previous chemotherapy for small cell lung cancer were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cyclophosphamide (500 mg/m2, i.v., on day 1, and 350 mg/m2, i.v., on day 8), vincristine (1 mg/m2, i.v., on day 1) and methotrexate (20 mg/m2, i.v., on days 1 and 8). This chemotherapy regimen was repeated at 3- or 4-week intervals. Among 20 evaluable patients, none showed complete response but 14 (70%) showed a partial response, with a median response duration of 8 weeks (range, 4-20 weeks). The median survival time for the 20 evaluable patients was 28 weeks. Toxicity included mild to moderate hematologic toxicity, alopecia and nausea and vomiting. This combination chemotherapy appears to be suboptimal for the treatment of small cell lung cancer, with no complete responses and a relatively short median survival time.

Adult↗

Depressed cellular immunity in Mycoplasma pneumoniae pneumonia.

We studied the lymphocytes and serum suppressive factor in patients with Mycoplasma pneumoniae pneumonia. Skin testing for delayed hypersensitivity to tuberculin was performed in 44 patients with pneumonia associated with M. pneumoniae infection. These patients were tuberculin-positive. Twenty-five patients showed a transient negative tuberculin reaction in the acute stage and 19 had a positive reaction. In tuberculin-negative patients, peripheral blood T lymphocytes were not significantly reduced; however, the blastogenic lymphocyte response to purified protein derivative (PPD) and PPD-induced gamma-interferon production were significantly reduced when compared with those in tuberculin-positive patients and healthy tuberculin-positive controls. The lymphocyte response of healthy tuberculin-positive controls was not suppressed by adding the serum of the tuberculin-negative patients. These results suggest that tuberculin anergy in patients with M. pneumoniae pneumonia early after clinical onset is due to depressed lymphocyte functions and not to serum factors.

Adolescent↗

Determination of the T-cell subset producing gamma-interferon in tuberculous pleural effusion.

The percentage of cells of different T-cell subsets and their functions in tuberculous pleural effusion were investigated. The percentage of OKT4-positive cells was 65 +/- 2% (mean +/- SEM, n = 8) and that of OKT8-positive cells was 19 +/- 3% (n = 8). Pleural T lymphocytes of patients with tuberculous pleurisy responded well to stimulation with purified protein derivative of tuberculin, and deoxyribonucleic acid synthesis was observed along with gamma interferon (IFN-gamma) production. When pleural T lymphocytes of patients with tuberculous pleurisy were treated with OKT4 monoclonal antibody and complement, a significant decrease in IFN-gamma production was observed in all eight patients (P less than 0.005), whereas no definite decrease in IFN-gamma production was found after treatment with OKT8 monoclonal antibody and complement. These results suggest that at least the OKT4+/OKT8- T-cell subset is responsible for the antigen-specific IFN-gamma production in pleural T lymphocytes of patients with tuberculous pleurisy.

Adult↗