Biological activities of novel polyether antifungals, gambieric acids A and B from a marine dinoflagellate Gambierdiscus toxicus.
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Amphotericin B↗
Biomedical subjects
K Yazawa
Publications and source records attributed to K Yazawa.
The Tokyo Metropolitan Home Vision Screening Program for amblyopia in 3-year-old children.
In August 1989, the Tokyo Metropolitan Government officially began a vision screening program for children aged 3 years 1 month. A 1988 pilot study of 1,303 children this age disclosed five cases (0.38%) of amblyopia. The home vision test, which uses picture cards of familiar figures, proved to be an efficient and inexpensive method of screening when incorporated into the existing health-check program for 3-year-old children. In the initial eight months of the program, 21,906 children were screened. Of these, 419 children (1.9%) were referred to an ophthalmologist for follow-up, and amblyopia was detected in 41 children (0.19%).
Amblyopia↗
Comparative studies on the postantifungal effect produced by the synergistic interaction of flucytosine and amphotericin B on Candida albicans.
A turbidometric method was used to measure Candida albicans yeast cell growth and to quantitate the postantifungal effect (PAFE) after exposure to various concentrations of flucytosine and amphotericin B, alone and in combination, for 2 hr at 30 degrees C. The drug concentrations used in the PAFE assays were determined by initial MIC and FIC (fractional inhibitory concentration) evaluations. The PAFE was calculated by the difference in time (hr) required for growth of the control and test cultures to reach the 0.5 absorbance level following removal of the drug by dilution. A synergistic PAFE was evidenced with combinations of the two drugs at concentrations below their individual MICs. Combinations of flucytosine (0.012 to 0.049 micrograms ml-1) and amphotericin B (0.195 to 0.39 micrograms ml-1) produced PAFEs ranging from 6.3 to 21.8 hr. These PAFEs persisted from 0.3 to 14.7 hr longer than those achieved when each of the two agents was assayed separately.
Amphotericin B↗
Light and electron microscopic studies on experimental nocardia-toxicosis in mice.
An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs.
Aged↗
Synergistic postantifungal effect of flucytosine and fluconazole on Candida albicans.
The in vitro efficacy of flucytosine and fluconazole, separately and in combination, with respect to induction of a postantifungal effect (PAFE) on Candida albicans was studied. PAFE refers to the persistent suppression of fungal cell growth following a short period of exposure to an antifungal agent. A turbidometric method was used to measure cell growth and to quantitate the PAFE following exposure of C. albicans yeast cells to different concentrations of the two agents for 2 h. The PAFE was determined by the difference in time (h) required for growth of the control and test cultures to increase to the 0.5 absorbance level following removal of the drug by dilution. Minimum (MIC) and fractional inhibitory concentration determinations were made and the data used for selecting the concentrations used in the PAFE evaluations. A synergistic interaction of the two drugs at concentrations well below their individual MICs was evidenced. Flucytosine:fluconazole ratios of 1:16-1:32 at concentrations ranging from 0.024-0.098 micrograms ml-1 and from 0.78-1.56 micrograms ml-1, with flucytosine and fluconazole, respectively, induced PAFEs which persisted for 2.5 h longer than those achieved when each of the two agents was assayed separately.
Candida albicans↗
The postantifungal effect of 5-fluorocytosine on Candida albicans.
The in-vitro postantifungal effect (PAFE) of 5-fluorocytosine for Candida albicans for short periods of time was investigated. Yeast cells were exposed for 0.5, 1 or 2 h to a range of concentrations (0.1-3.2 mg/L) of 5-fluorocytosine. The PAFE was quantitated by determinations of the number of colony forming units at hourly intervals (0-10 h) after removal of the drug by dilution. The length of the PAFE was dependent upon the concentration of 5-fluorocytosine and the duration of exposure. An exposure time of 0.5 h resulted in PAFE's ranging from 0 to 4.2 h. Exposure times of 1 and 2 h resulted in longer PAFEs and in many instances suppression of cell growth was seen for the entire evaluation period (up to ten hours).
Candida albicans↗
In-vitro activity of new carbapenem antibiotics: comparative studies with meropenem, L-627 and imipenem against pathogenic Nocardia spp.
MICs of two new carbapenems, meropenem and L-627, and imipenem were determined against 98 strains of the Nocardia asteroides group (i.e. N. asteroides sensu stricto, Nocardia farcinica and Nocardia nova), 46 strains of Nocardia brasiliensis and 17 strains of Nocardia otitidiscaviarum. Meropenem and L-627 were less active against the N. asteroides group than imipenem. Among the three species of the N. asteroides group, N. nova was the most sensitive to all the carbapenems. Meropenem was more active than imipenem against both N. brasiliensis and N. otitidiscaviarum with MIC50 values of 28.3-53.3 mg/L. L-627 was less active than meropenem.
Carbapenems↗
The producer and biological activities of SO-75R1, a new mutactimycin group antibiotic [corrected].
The producer of SO-75R1, a new anthracycline group antibiotic was identified as Nocardia brasiliensis. SO-75R1 was active against Gram-positive bacteria, but not active against Gram-negative bacteria or fungi. All tested Nocardia brasiliensis strains as well as the producer itself were resistant to SO-75R1, although four other pathogenic Nocardia, i.e. N. asteroides, N. nova, N. farcinica and N. otitidiscaviarum were sensitive [corrected].
Animals↗
SO-75R1, a new mutactimycin derivative produced by Nocardia brasiliensis.
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Anthracyclines↗
[Cardiac performance in total anomalous pulmonary venous connection].
Cardiac performance in 54 patients with total anomalous pulmonary venous connection was investigated by cardiac catheterization before and after surgery. 51 patients underwent intracardiac repair, and 17 of them died during or immediately after operation. According to the preoperative study, the left ventricular ejection fraction (LVEF) of surviving patients was significantly higher than that of patients who died, and the pulmonary arterial mean pressure of surviving patients was significantly lower than that of patients who died. However, there was no significant difference between the left ventricular end-diastolic volume (LVEDV), right ventricular ejection fraction (RVEF), and right ventricular end-diastolic volume (RVEDV) in surviving patients and those who died. Post-operative catheterization studies showed significant increases of LVEF and LVEDV compared to pre-operative figures. RVEF and RVEDV and pulmonary arterial mean pressure decreased significantly after surgery. It was concluded that preoperative cardiac performance of surviving patients was better than that of those who died, and post-operative cardiac performance of surviving patients was basically normal.
Blood Pressure↗
Inactivation of kanamycin A by phosphorylation in pathogenic Nocardia.
Among the five species of pathogenic Nocardia, i.e., N. asteroides, N. brasiliensis, N. farcinica, N. nova and N. otitidiscaviarum, all strains of N. brasiliensis and N. farcinica showed resistance to an aminoglycoside antibiotic, kanamycin A, showing the MIC (minimum inhibitory concentration) values of more than 100 micrograms/ml. This species-specific difference in sensitivity was found to be explained by the production of an inactivation enzyme, aminoglycoside 3'-phosphotransferase APH(3'). Structural studies by mass and NMR spectroscopy on the inactivated substance produced by a cell-free extract of the Nocardia confirmed the conversion of kanamycin A to an inactive substance, kanamycin A 3'-phosphate. The MIC values of N. otitidiscaviarum and N. nova for kanamycin A, on the other hand, ranged from 0.78 micrograms/ml to 100 micrograms/ml, and both species were non-producers of APH(3'). Sensitivity to the antibiotic and APH(3') productivity of N. asteroides varied depending on the strain.
Carbohydrate Sequence↗
Cardiovascular findings in familial hypercholesterolemic children.
Four child patients (1 male and 3 females) with homozygous familial hypercholesterolemia (FH) were examined. They were 4y4m to 9y8m of age on admission. A female patient at age 5y7m on admission had already experienced anginal attacks. Ischemic change was found on exercise ECG in 2 patients. Grade 1/6 to 3/6 (Levine) systolic ejection type murmur was audible in all patients. Cardiac catheterization was carried out in all patients. Supravalvular aortic stenosis was found and so-called atherosclerotic wall thickening was also noticed in 3 of them. Narrowing of the coronary arteries was found in only 1 patient who complained of anginal pain. Supravalvular aortic stenosis was more prevalent than coronary artery disorders in FH children and this lesion was also detected by echocardiography. Therefore, follow-up by echocardiography seems to be very useful in assessing the progression of atherosclerosis in patients with severe hypercholesterolemia.
Aortic Valve Stenosis↗
Antifungal activity of SL-1, a beta-nitrostyrene type pigment and its synthetic congeners.
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Antifungal Agents↗
A toxic substance produced by Nocardia otitidiscaviarum isolated from cutaneous nocardiosis.
During our studies on toxic substances from clinically isolated Nocarida, a new isolate identified as Nocardia otitidiscaviarum from cutaneous nocardiosis was found to produce a toxic substance called HS-6 that had strong in vitro as well as in vivo toxicity. The mouse intraperitoneal LD50 value was 1.25 mg/kg and the ED50 value for L1210 cultured cells was 0.3 ng/ml. The structure of HS-6 was determined and found to belong to the 16-membered macrocyclic group with a molecular formula of C43H68O12. HS-6 also showed activity against pathogenic fungi such as Cryptococcus neoformans.
Aged↗
Congenital nemaline myopathy with dilated cardiomyopathy: an autopsy study.
A 3-year-old boy with congenital nemaline myopathy had generalized muscle weakness and hypotonia since birth. He developed cardiac symptoms at 2 years of age and died from congestive heart failure. At autopsy, the heart was markedly dilated, involving both ventricles. Rod bodies were recognized not only in skeletal muscles but in cardiac muscles on light and electron microscopy. Desmin and alpha-actinin, which constitute Z-line protein, were shown to localize in the rod structures in both skeletal and myocardial cells by immunohistochemistry. Seven cases of nemaline myopathy with cardiomyopathy have been reported in the literature. All of these patients were over 20 years of age, and the condition appeared mostly in the adult onset and the asymptomatic forms. This is the first infantile case of congenital nemaline myopathy which showed dilated cardiomyopathy with a fatal outcome.
Cardiomyopathy, Dilated↗
Mechanism of receptor-mediated modulation of the delayed outward potassium current in guinea-pig ventricular myocytes.
1. Receptor-mediated modulation of the delayed outward potassium current (IK) was investigated in guinea-pig single ventricular cells by using whole-cell voltage clamp and intracellular dialysis. 2. Isoprenaline increased IK in a dose-dependent manner with a half-maximum dose of 1.8 X 10(-8) M. Isoprenaline (10(-6) M) maximally increased IK by a factor of 2.85. This effect did not depend on the concentration of intracellular Ca2+ [( Ca2+]i). 3. External application of 10(-5) M-forskolin and internal application of 5 X 10(-5) M-cyclic AMP or 5 X 10(-6) M of the catalytic subunit of cyclic AMP-dependent protein kinase (PKA) also increased IK about 3-fold. The effect of isoprenaline on IK was masked by previous application of cyclic AMP. 4. All the above phosphorylating agents increased the amplitude of IK without a significant change in the current kinetics. 5. In the presence of 10(-5) M-forskolin, an additional application of 10(-8) M-12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C (PKC), produced a further increase in IK, suggesting that the active sites of PKA and PKC on the IK channel are different. 6. Acetylcholine (10(-6) M) suppressed IK when the current was previously enhanced by 2 X 10(-8) M-isoprenaline, but had little effect in the absence of isoprenaline. 7. We conclude that beta-adrenergic modulation of IK is mediated by cyclic AMP-dependent phosphorylation but not by an increase in [Ca2+]i, that PKA and PKC enhance IK independently, and that acetylcholine antagonizes beta-adrenergic stimulation of IK most probably by inhibiting adenylate cyclase.
Acetylcholine↗
An improved method for isolating cardiac myocytes useful for patch-clamp studies.
An improved method for isolating cardiac myocytes is described. This method consists of the initial dispersion of the myocytes with a new type of collagenase and the following treatment of the cells with a non-specific protease. This method gives more than 80% rod-shaped, viable, and quiescent cells, which are suitable for biochemical as well as electrophysiological experiments. Formation of a G omega seal and subsequent whole-cell recording is easily performed using these cells.
Animals↗
[Diagnosis of myocardial ischemia in patients with a significant coronary arterial stenosis following Kawasaki disease].
We evaluated the validity of body surface mapping (MAP) in assessing noninvasively the degree of myocardial ischemia in patients with significant coronary arterial stenosis following Kawasaki disease. Delay of ventricular depolarization was examined by a departure map (DM) using mean QRS map, and the sensitivity of this method in detecting myocardial ischemia was evaluated based on the findings of coronary arteriography (CAG). The other noninvasive measures were also evaluated. MAP was obtained in 29 patients with significant coronary arterial stenotic lesions, including coronary occlusion, segmental stenosis and localized stenosis of 75% or greater. Mean QRS map was obtained based on MAPs in 41 children without organic heart disease and in 22 patients with significant stenotic lesions. The departure index (DIi) was calculated by subtracting potentials at each lead from those of the mean QRS maps and divided by the standard deviation. Departure area (Da) was defined as an area with DIi of -2 or less. Each MAP was subdivided into nine sections, and Da greater than or equal to one-eighth of the anterior wall section, Da greater than or equal to one-third of the posterior and inferior wall sections or Da greater than or equal to half of the other sections were regarded as ischemic areas. Sensitivity in detecting ischemia by MAP was assessed by the CAG findings, which was also compared to the sensitivity of the electrocardiograms (ECG), ECG with dipyridamole administration (Dp-ECG), vectorcardiograms (VCG), Holter ECG (Holter), treadmill test (TM), Master's double step test (MD), two-dimensional echocardiography (2DE) and thallium myocardial imaging (TMI).(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗