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Biomedical subjects

G Tamura

Publications and source records attributed to G Tamura.

At least 271 records · Page 15Linked to original sources

Biologically active polycycloalkanes. 6. Antiviral 1-tricyclo[4.3.1.1 2,5]undecyl derivatives.

Functionalization reactions via cationic intermediates of tricyclo[4.3.1.1 2,5]undecane (2) were investigated to prepare derivatives with potential antiviral activities. Bromination of 2 took place regiospecifically at C-1, and the resulted bromide 5 was converted into the hydroxide 9, the carboxylic acid 12, and the amine 22, from which were synthesized a variety of secondary derivatives, including homologous esters 10 and 20, amides 14 and 19, carbamates 24, and ureas 17 and 25. The hydroxide 9, the acid 12, and the acetamide 21 were also obtainable directly from tricyclo[5.2.1.0 2,6]dec-endo-2-ylcarbinol (1), the precursor for the synthesis of the hydrocarbon 2. Success in these functionalization-rearrangements was attributed to the inability of the intermediate 2-1-yl cation (2+) for further skeletal isomerizations. Among the 1-substituted derivatives of 2 prepared, the amine hydrochlorides (16 and 23), a few esters (20b and 20d), and some N-alkylamides (19c, 19d, and 19e) exhibited marked antiviral activities as compared to amantadine hydrochloride, when tested in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus.

Animals↗

High and selective resistance to mecillinam in adenylate cyclase-deficient or cyclic adenosine 3',5'-monophosphate receptor protein-deficient mutants of Escherichia coli.

Adenylate cyclase-deficient (cya) mutants of Escherichia coli K-12 were selectively and highly resistant to mecillinam (FL1060) among several beta-lactam antibiotics in the absence of cyclic adenosine 3',5'-monophosphate (cAMP). They became sensitive to the drug in the presence of cAMP. Also, cAMP receptor protein-negative (crp) mutants, with the exception of strain 5333, were highly resistant to mecillinam in the presence and in the absence of cAMP. Mecillinam exerted two distinct and sequential effects in both cya+ strains and cya strains supplemented with cAMP: (i) rounding of cells and (ii) cessation of cell division. The first effect was accompanied by a decrease in growth rate, whereas the second effect was accompanied by enlargement and lysis of the rounded cells. The second effect of mecillinam was dependent on inoculum size and cAMP. When the cell density was above about 10(6) cells per ml, the rounded cells stopped dividing but did not lyse. In the absence of cAMP, cya strains neither stopped dividing nor lysed; they were resistant to the second, lethal effect of mecillinam.

Adenylyl Cyclases↗

Effects of adrenergic agonists and antagonists on immediate cutaneous reactions in bronchial asthma.

Asthmatic patients who showed an allergic skin reaction to house-dust antigen (HD) were injected intradermally with a mixture of HD and a various dose of isoproterenol (Isopr) or propranolol (Propr). In some cases Isopr clearly suppressed the formation of the wheal, but in some others Isopr did not much affect the allergic skin reaction. Also Propr increased markedly the skin reaction of some patients, or had little effect on it. The sensitivity of the skin of asthmatic patients to these drugs was closely correlated with the general response of the patients to adrenaline, such as changes in heart rate, diastolic blood pressure, blood glucose level, and blood triglyceride level.

Adrenergic Agonists↗

The relationship between the arterial level of angiotensin-converting enzymes and arterial gas tension in bronchial asthma.

To study the mechanism which causes a lowered serum level of angiotensin-converting enzyme (ACE) in asthma patients, the changes in serum ACE in arterial blood gas tension was measured. Serum ACE was also determined in patients with chronic obstructive lung disease (COLD) and fibrosing lung disease (FLD). A reduced level of serum ACE was found in some patients with COLD, similar to that in patients with asthma. A significant relationship existed between the lowered serum ACE level and the degree of arterial hypoxia, especially in asthmatic patients and some patients with COLD. The significance of lowered serum ACE is discussed in relation to the pathogenesis and the mechanism of hypoxemia in patients with asthma, COLD and FLD.

Asthma↗

The effect of sympathomimetic drugs on immediate skin reactions and metabolic responses in asthmatic patients.

The varied effects of intradermal injection of isoproterenol and propranolol on the immediate skin reaction were studied in relation to the metabolic responses to the intravenous injection of epinephrine. In asthmatic patients whose skin reaction was not suppressed with 10(-7) M isoproterenol, the hyperglycemic response after the injection of epinephrine was significantly reduced.

Adolescent↗

Glycosylation of interferons. Effects of tunicamycin on human immune interferon.

Human immune interferon, induced in leukocytes by phytohemagglutinin, was prepared in the absence and presence of tunicamycin, an antibiotic which selectively inhibits the glycosylation of newly synthesized glycoproteins. Interferon preparations, produced in the absence of the antibiotic, displayed a considerable chromatographic heterogeneity on: (a) concanavalin A-agarose, (b) phenyl-agarose, (c) Cibacron Blue F3GA-agarose, and (d) polyuridylic acid-agarose. This heterogeneity was completely eliminated when tunicamycin (2 microgram/ml) was present during induction of interferon; all activity was then recovered in the breakthrough fractions from all sorbents. The level of interferon activity in leukocyte culture fluid was not affected by tunicamycin within the range of concentration 0.05 to 2.0 microgram/ml. These data indicate that (a) human immune interferon undergoes glycosylation, and tunicamycin is an effective inhibitor of this process. Thus, it appears that (b) at least some of the carbohydrates of human immune interferon are N-glycosidically linked. Moreover, it seems that (c) glycosylation is not necessary for an interferon molecule to either be secreted by the cell or (d) to express its antiviral function. Such properties of human immune interferon as (e) the apparent hydrophobicity and (f) an affinity for a polyribonucleotide are conferred only when its glycosylation is unimpaired.

Glucosamine↗

Funiculosin, a new antibiotic. II. Structure elucidation and antifungal activity.

Structure elucidation and some biological properties of an antiviral and antifungal antibiotic, funiculosin, are summarized. Funiculosin is a derivative of N-methyl-4-hydroxy-3, 5-disubstituted-2-pyridone containing a novel substituent, cyclopentanetetrol moiety, that is reported here for the first time in a natural product. The antibiotic protects guinea pigs efficiently against experimental trichophytosis. Toxicity of funiculosin is unique and highly selective for animal species.

Animals↗

Biological active polycycloalkanes. 4. Phosphoric esters of trimethylenenorbornyl alcohols.

Secondary (6) and tertiary (8) phosphates of exo-5,6-trimethylenenorborn-exo-2-yl alcohol (exo-tricyclo-[5.2.1.0(2,6)]dec-exo-8-yl alcohol, 3) and a secondary ester (9) of a mixture of exo-tricyclo[5.2.1.0(2,6)]dec-3-en-8- and -9-yl alcohol (2) were prepared. The most convenient route to 6 was direct esterification of phosphoric acid with 3. 9 was obtainable by the addition of phosphoric acid to endo-dicyclopentadiene (1). These phosphates were tested in vitro for antiviral activity against Newcastle disease virus using a monolayer culture of chick embryo fibroblasts. 6 was found ca. twice more potent than, while 8 was as active as, amantadine hydrochloride under the present test conditions.

Animals↗

Properties of proteins produced after damage to deoxyribonucleic acid of Escherichia coli.

Large amounts of extra proteins, X (in the envelope fraction) and X' (in the cytoplasmic fraction) were detected by SDS-polyacrylamide gel electrophoresis when DNA of Escherichia coli was damaged. These two proteins had the same apparent molecular weight (appproximately 40,000) and were produced under identical conditions, including requirement for the recA" and lexA+ genotype. Sucrose density gradient centrifugation revealed that protein X' consisted of relatively large and heterogeneous aggregates in the cytoplasmic fraction; the distribution of protein X in the envelope was not determined. As proteins X and X' were shown to be equivalent, it is suggested that they are identical. Co-precipitation of the aggregates of protein X' with the envelope led to the appearance of protein X in the envelope fraction.

Bacterial Proteins↗

Cysteine synthase from rape leaves.

Cysteine synthase [O-Acetyl-L-serine acetate-lyase (adding hydrogen-sulfide) EC 4.2.99.8] has been highly purified from the extract of rape, Brassica chinensis var. Komatsuna. The purified preparation appeared to be homogeneous on Sephadex G-100 gel filtration and dodecylsulfate-polyacrylamide gel electrophoresis, showing a molecular weight of about 62,000. The latter method also suggested that this enzyme was composed of two identical subunits. The enzyme contained 2 moles of pyridoxal phosphate per mole of enzyme.

Chromatography, Gel↗

Mutant of Escherichia coli with thermosensitive protein in the process of cellular division.

A new thermosensitive mutant of Escherichia coli deficient in cell division was isolated by means of membrane filtration after nitrosoguanidine mutagenesis. The mutant cells grow normally at 30 C but stop dividing immediately after shift to 42 C, resulting in multinucleated filaments lacking septa. The number of colony-forming units does not decrease for at least 6 hr at 42 C. The maximum length of the filaments is 10 to 16 times that of normal cells. Addition of a high concentration of NaCl fails to stimulate cell division at 42 C. The filaments formed at 42 C divide abruptly 30 min after shift to 30 C, and synchronous increase of cell number is shown for 3 hr. The macromolecular synthesis of protein and nucleic acids at 42 C is normal on the whole. The cell division shown after the shift from 42 to 30 C is observed in the absence of thymine, but not in the presence of chloramphenicol or in a medium deficient in amino acids. However, the filament can divide to some extent in the presence of chloramphenicol if some protein synthesis is allowed to proceed at 30 C before the addition of the antibiotic. The elongated cells divide at 42 C provided that they are exposed to 30 C before being shifted to high temperature.

Adenine↗