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Biomedical subjects

H Okazaki

Publications and source records attributed to H Okazaki.

At least 289 records · Page 16Linked to original sources

Semisynthetic beta-lactam antibiotics. I. Synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties.

The synthesis and antibacterial activity of new ureidopenicillin derivatives having catechol moieties in the 6-acyl side chain are described. These compounds showed remarkably strong activities against Pseudomonas aeruginosa. Especially, 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-methyl-1-ureido]-2- phenylacetamido]penicillanic acid (7a) had the most potent activity in vitro against Gram-negative bacteria, its activity being 30 approximately 60-fold greater than that of piperacillin against most strains of P. aeruginosa.

Animals↗

Semisynthetic beta-lactam antibiotics. II. Effect on antibacterial activity of ureido N-substituents in the 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-1- ureido]-2-phenylacetamido]penicillanic acids.

The synthesis and the relationship between in vitro and in vivo activities of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-R1-1-ureido]-2- phenylacetamido]penicillanic acids having C2 approximately 8 alkyl or substituted alkyl groups as the substituents (R1) are described. In this series, 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido] -2-phenylacetamido]penicillanic acid (1b, AO-1100) showed the most potent protective effect on mice in experimental Pseudomonas aeruginosa infections, although it did not have the strongest in vitro activity among the penicillins we synthesized.

Animals↗

Meningio-angiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles.

We report six cases of meningio-angiomatosis, a disorder of the cerebral cortex of probable malformative origin frequently associated with neurofibromatosis and either asymptomatic or associated with a seizure disorder. The patients, three males and three females, ranged from 10 to 70 years of age at diagnosis. The lesion was an incidental autopsy finding in two patients; four subjects had a seizure disorder which improved following surgical resection of the cortical lesion. In five instances the process was unifocal; one patient with neurofibromatosis had multifocal involvement. Grossly, the lesions were firm, sharply demarcated, transcortical plaques with leptomeningeal calcifications in five cases. The cortical plaques showed characteristic features of meningio-angiomatosis, i.e. a circumscribed, proliferating microvasculature with perivascular meningothelial cell proliferation and fibrosis. In five cases Alzheimer's neurofibrillary change in neurons was present both within the plaques and in the surrounding cortex. Neither senile plaques nor granulovacuolar degeneration were noted. Electron microscopy in one case demonstrated typical intraneuronal accumulations of neurofilaments with regular constrictions. Intracortical vessels lined by endothelial cells with tight junctions were surrounded by pericytes and meningothelial cells. The significance of neurofibrillary tangles described in a variety of disorders, and the factors stimulating their production in the present cases are unknown.

Adolescent↗

Emeriamine, an antidiabetic beta-aminobetaine derived from a novel fungal metabolite.

Emeriamine [(R)-3-amino-4-trimethylaminobutyric acid], derived from a novel fungal metabolite "emericedin" [(R)-3-acetylamino-4-trimethylaminobutyric acid], was proved to be a strong and specific inhibitor of carnitine-dependent oxidation of long chain fatty acid (IC50; 3.2 X 10(-6)M) and its main inhibition site was shown to be carnitine palmitoyltransferase I located on the outer-surface of the mitochondrial inner membrane. Emeriamine also showed hypoglycemic and antiketogenic activities in a dose-dependent manner (1 - 10 mg/kg) when administered orally to fasted normal and diabetic animals.

Acyltransferases↗

The hypothalamus and pituitary in cerebral gigantism. A clinicopathologic and immunocytochemical study.

Cerebral gigantism, or Sotos' disease, is a rare disorder of unknown cause characterized by the early onset of excessive growth, acromegalic features, and some degree of mental retardation. Although several endocrinologic abnormalities have been described in such patients, none has been specific or sufficient to explain the clinical features. Our report of the endocrinologic and pathologic aspects in a young woman with Sotos' disease includes the first microanatomic study of the hypothalamus and immunocytochemical examination of the pituitary gland in this disorder.

Autopsy↗

Computed tomography in young children with herpes simplex virus encephalitis.

Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors.

Child, Preschool↗

A case of nonfunctioning paraganglioma arising from the retroperitoneum: angiographic and scintigraphic features.

We report a case of a nonfunctioning nonchromaffin paraganglioma arising from organ of Zuckerkandl. Angiography manifested a cartwheel-shaped image in the arterial phase and a characteristic tortoise shell-shaped lobular structure with homogeneous opacification in the venous phase. Just after administration of 99mtechnetium-E-HIDA scintigraphy disclosed a globular hot density below the left kidney. These findings may represent characteristic signs of paragangliomas.

Adult↗

Enhancement of DNA binding and mutagenicity of 1-nitropyrene by zinc acetate in Salmonella typhimurium TA100.

The effect of zinc acetate on the mutagenicity of 1-nitropyrene (1-NP) in Salmonella typhimurium TA100 was examined. By the pre-treatment of the cells with zinc ions (0.24 mM) the revertant colonies caused by 1.5 microM of 1-NP in the pre-incubation mixtures increased approximately 3-fold, while the survival colonies decreased to approximately 75% under the same conditions. The enhancing effect of zinc ions on the mutagenicity was not dependent on the increase of 1-NP incorporation into the cells. The addition of zinc ions to whole cell preparations had no enhancing effect on the 1-NP reductase activity. The effect of zinc acetate on the binding of [3H]1-NP to DNA in S. typhimurium TA100 was examined. The amount of [3H]1-NP bound to DNA increased by the pre-treatment of the cells with zinc ions. A good correlation was found between the extent of binding of 1-NP to DNA and the frequency of induced histidine reversions in the cells treated with zinc ions under the experimental conditions used.

Acetates↗

Contractile reserve of valvular heart diseases echocardiographically evaluated by epinephrine loading before and after cardiac surgery.

In order to evaluate cardiac contractile reserve, echocardiographic studies were performed on 59 patients with acquired valvular heart disease and 13 patients with atrial septal defect. After epinephrine loading, the 59 patients were classified into three groups. In group I, echocardiographically-obtained left ventricular posterior wall excursion (PWE) remained below 10 mm after the administration of 2 microgram/min epinephrine. This group included patients with PWE below 10 mm after 1 microgram/min epinephrine loading but who could not endure the 2 microgram/min infusion because of significant adverse effects. In group II, PWE was less than 10 mm before the loading, but exceeded 10 mm after the administration of 1 or 2 microgram/min epinephrine loading. In group III, PWE exceeded 10 mm without stress. The conclusions derived from our data are as follows: The PWE and mean left ventricular posterior wall velocity (mPWV) obtained by echocardiography reflect the stroke volume derived from the thermodilution technique. It is possible to estimate the cardiac contractile force in patients who have a paradoxical motion of the interventricular septum, in the preoperative and even in the early postoperative periods. Patients whose PWE and mPWV are less than 10 mm and 35 mm/sec, respectively, after 2 microgram/min loading of epinephrine (group I), are likely to have severe cardiac failure after surgery. Inotropic stimulation is considered to be a very useful indicator for prediction of cardiac contractile reserve. Patients having decreased PWE, mPWV, mVcf and EF before surgery may have arrested recovery in both short- or long-term follow-up. However, surgical treatment is recommended for these patients with low cardiac function, because some improvement can be expected after surgery.

Adult↗

Formadicins, new monocyclic beta-lactam antibiotics of bacterial origin. I. Taxonomy, fermentation and biological activities.

A Gram-negative bacterium produces new monocyclic beta-lactam antibiotics with a formylamino substituent, named formadicins A, B, C and D. The producing bacterium was taxonomically characterized and designated as Flexibacter alginoliquefaciens sp. nov. YK-49. Formadicins have narrow antibacterial spectra. They are highly active against some species of Pseudomonas, Proteus and Alcaligenes. Of the four, formadicin C shows the most potent antibacterial activity. Several amino acids such as glycine, D-alanine and D-leucine were antagonistic against formadicins. Formadicins, especially formadicins A and C having the formylamino substituent bound to the 3-position of a beta-lactam nucleus, were highly resistant to hydrolysis by various types of beta-lactamases. Formadicins A and C showed affinity for penicillin-binding proteins (PBPs) 1A and 1B in Pseudomonas aeruginosa IFO 3080, but formadicin B and nocardicin A showed affinity only for PBP 1B. Formadicins A and C did not lyse Escherichia coli LD-2 solely at their MICs, but when combined with mecillinam each induced a rapid lysis of this organism.

Amino Acids↗

Formadicins, new monocyclic beta-lactam antibiotics of bacterial origin. II. Isolation, characterization and structures.

New monocyclic beta-lactam antibiotics, formadicins A, B, C and D, were isolated from the culture filtrate of Flexibacter alginoliquefaciens sp. nov. YK-49 by various types of column chromatography and preparative reverse-phase HPLC. Their structures were determined by spectroscopic analyses and degradation studies. They have a nocardicin-type skeleton and a formylamino group at the 3- or 12-position. Formadicins A and B each have a D-glucuronide moiety and give formadicins C and D, respectively, upon hydrolysis using beta-D-glucuronidase.

Anti-Bacterial Agents↗

Cephabacin M1-6, new 7-methoxycephem antibiotics of bacterial origin. I. A producing organism, fermentation, biological activities, and mode of action.

New 7-methoxycephem antibiotics were found in culture filtrates of a bacterium isolated from a plant and named cephabacin M1-6. They are the first members of 7-methoxycephem antibiotics of bacterial origin. The producing organism was taxonomically characterized and identified as Xanthomonas lactamgena YK-431; other strains of this species have recently been reported to produce cephabacin F and H group antibiotics. Cephabacin M1-6 exhibited moderate antibacterial activity against Gram-negative and Gram-positive bacteria. Cephabacin M1-6 were as stable as cephamycin C to cephalosporinases. They showed inhibitory activity against a cephalosporinase of Proteus vulgaris GN 4413. The mode of action of cephabacin M1 was examined using Escherichia coli and Bacillus subtilis as test organisms; primary lethal targets of cephabacin M1 are penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis.

Anti-Bacterial Agents↗