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T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 217 records · Page 12Linked to original sources

Purification and analysis of the structure of alpha-galactosidase from Escherichia coli.

Alpha-Galactosidase, the product of the melA gene, was purified from a strain of Escherichia coli harboring a plasmid carrying melA, which over-produced the alpha-galactosidase. An apparent molecular weight was determined to be 50 kDa. The amino acid composition of this enzyme was determined. The result indicates that this enzyme is a hydrophilic and acidic protein. We have subjected the purified enzyme to 20 cycles of N-terminal sequence analysis. This verified the translation start site of the melA gene and the predicted N-terminal sequence.

Amino Acid Sequence↗

Synthesis and antitumor activity of quaternary ellipticine glycosides, a series of novel and highly active antitumor agents.

A series of ellipticine glycosides [2-N-glycosyl quaternary pyridinium salts of three ellipticines: ellipticine (1), 9-methoxyellipticine (2), and 9-hydroxyellipticine (4)] were stereoselectively synthesized in good yields by an improved condensation reaction between ellipticines [1, 2, and 9-acetoxyellipticine (3)] and protected (peracylated and perbenzylated) glycosyl halides with cadmium carbonate, followed by deprotection. These glycosides were preliminarily evaluated for their antitumor activity in the L1210 leukemia system. Twenty-six (53%) of the 49 glycosides tested were curative, and five [9-hydroxyellipticine L-arabinopyranoside (41b), D-lyxofuranoside (43a), L-lyxopyranoside (44b), D-xylofuranoside (49a), and L-rhamnopyranoside (56)] were selected for extended evaluation on the basis of their high levels of activity. The structure-activity relationships are discussed. The selected glycosides showed remarkable activity in six different murine tumor systems with excellent therapeutic ratios; their efficacy surpassed that of doxorubicin against three of these systems. On the basis of these results and ease of formulation, the two glycosides 41b (SUN4599) and 49a (SUN5073) were selected for further preclinical evaluation and possible clinical development.

Alkaloids↗

Results of a dental fear survey in Japan: implications for dental public health in Asia.

The purpose of this investigation was to initiate the study of dental fear in Japan. 415 college students, aged 18-22 yr were surveyed. A standardized questionnaire which has been used in the United States was translated into Japanese and was administered to the students. More than 80% of those surveyed reported some dental fear. Six to 14% of the students reported extreme fear of the dentist. The majority of the subjects admitted that they delayed making dental appointments due to fear. Muscle tension was the most common physiological symptom reported. The dental drill and needle were the most fear-provoking stimuli.

Adolescent↗

Kinetic study of a change in intracellular ATP level associated with aerobic catabolism of ethanol by Streptococcus mutans.

Streptococcus mutans, a group of lactic acid bacteria and a normal inhabitant of the human oral cavity, generates ATP by substrate-level phosphorylation coupled to oxidation of ethanol (an end product of fermentation of sugars) into acetate in the presence of oxygen (K. Fukui, K. Kato, Kodama, H. Ohta, T. Shima moto, and T. Shimono, Proc. Jpn. Acad. 64B:13-16, 1988). Kinetic measurements were made of the cellular responses of S. mutans FA-1 to ethanol in comparison with those to glucose. In contrast to oxygen-independent acid production from glucose, oxygen was absolutely required for acid production from ethanol. Ethanol elicited a marked increase in the intracellular ATP concentration (ATPi) from a starved level to a steady level which was held constant as long as oxygen was present in the medium. Once oxygen was exhausted, ATPi returned to the starved level without delay. On the contrary, ATPi changes induced by glucose, which were independent of oxygen, followed a rather complicated time course before a steady level was established. Both the steady ATPi and the rate of accompanying oxygen consumption were functions of the ethanol concentration. These two parameters were linearly correlated, indicating that the unimolecular ATP turnover rate, which is independent of the rate of ATP generation in the steady state, can be calculated for cells energized by ethanol. The estimated turnover rate was 1.5 s-1 at 37 degrees C, which is comparable to that for other bacteria energized by glucose under nongrowing conditions.

Adenosine Triphosphate↗

Characterization of a novel L-serine transport system in Escherichia coli.

A novel transport system for L-serine was found in Escherichia coli cells grown on medium containing amino acid mixture. This novel system is distinguishable from the known three transport systems for L-serine, namely, the serine-threonine system, one of the leucine-isoleucine-valine systems, and the glycine-alanine system. Uptake of L-serine via this novel system was inhibited by none of the amino acids tested, indicating that it is highly specific for L-serine. This system was induced by L-leucine, but not by L-serine. The Km for L-serine was 50 microM, and the Vmax was 23 nmol/min per mg of cell protein. Transport of L-serine via this system was strongly inhibited by KCN, an inhibitor of the respiratory chain, or by carbonyl cyanide m-chlorophenylhydrazone, an H+ conductor. Uptake of H+ was induced by L-serine influx. These results indicate that an H+-serine cotransport mechanism is operative in this novel L-serine transport system.

Alanine↗

[Cis-platinum, vincristine and peplomycin (CVP) therapy for carcinoma of the uterine cervix].

Surgery and radiation therapy are major treatments for carcinoma of the uterine cervix. However, there has been little improvement in survival recently. Since 1982, we have introduced multiagent chemotherapy consisting of cis-platinum, vincristine and peplomycin (CVP) to control systemic disease and to do cytoreduction prior to operation and/or radiation therapy. Our results are as follows. Thirty-one patients have been treated with CVP. Among eleven patients initially treated with CVP, 7 patients responded well to this regimen alone, including three patients who entered complete clinical remission. This indicates that this regimen is effective against carcinoma of the uterine cervix. Two patients who were thought to be candidates for radical hysterectomy became able to have less extensive surgery following CVP treatment. It is difficult for this CVP combination to control bulky tumors within previously radiated fields, probably because of poor vascularity due to pelvic fibrosis caused by radiation. Metastatic disease were also able to be controlled by this combination especially in two patients with pulmonary metastases. Nausea, vomiting and mild myelosuppression were frequently encountered, but they were tolerated well by the patients. However, great care must be taken in using peplomycin when the cumulative dose becomes large.

Adult↗

Construction of a vector for the study of regulatory mechanism of gene expression and its utilization in the melibiose operon of Escherichia coli.

We constructed a vector to evaluate terminator or attenuator of transcription quantitatively. This vector is a plasmid possessing lac promoter-polylinker-CAT(chloramphenicol acetyltransferase) gene. DNA fragment of interest can be inserted into the polylinker site, and the effect of the DNA fragment on the expression of the downstream gene is evaluated from the CAT activity. We analyzed gene expression of the melibiose operon of Escherichia coli using this plasmid, and found that a DNA fragment containing a large stem-loop structure with boxA sequence in it, which was present between melA and melB, caused strong reduction of gene expression. This DNA portion seems to be responsible for reduced expression of melB, the second gene of the melibiose operon.

Cloning, Molecular↗

One-month release injectable microcapsules of a luteinizing hormone-releasing hormone agonist (leuprolide acetate) for treating experimental endometriosis in rats.

Leuprolide acetate is a highly potent analog of luteinizing hormone-releasing hormone. We have prepared 1-month release injectable microcapsules of leuprolide acetate using a biodegradable polymer, poly (dl-lactide-co-glycolide), to treat an endocrine-dependent tumor, prostate cancer. In the present study, the possibility using the microcapsules to treat endometriosis was investigated. In rats, the microcapsules exhibited a pseudo-zero order release from the injection site for 1 month after being administered s.c. and i.m., and maintained effective constant serum levels of the analog during the 4-week treatment. A single injection of the microcapsules (100 micrograms/kg/day as leuprolide acetate) suppressed luteinizing hormone, follicle-stimulating hormone and estradiol for more than 4 weeks, and caused a dramatic regression of growth of Jones experimental endometriosis model in female rats. These results encourage the belief that a 1-month release parenteral preparation of leuprolide acetate may be potentially useful in the therapy of endometriosis in human beings.

Animals↗

Properties of a Na+-coupled serine-threonine transport system in Escherichia coli.

Based on the following experimental results we conclude that the serine-threonine transport system in Escherichia coli is a Na+-coupled cotransport system. (1) Addition of serine to cell suspensions induced H+ efflux in the presence of Na+. (2) Addition of serine to cell suspensions induced Na+ uptake by cells. (3) Imposition of an artificial electrochemical potential of Na+ in starved cells induced serine uptake. Some of these phenomena were observed when threonine was added instead of serine or inhibited when cells were preincubated with threonine. The Na+/serine (threonine) cotransport system was considerably repressed when cells were grown on a mixture of amino acids. Serine transport in cells grown in the absence of amino acids mixture was stimulated by Na+. The half maximum concentration of Na+ was 21 microM. Sodium ion increased the Vmax of serine transport without affecting the Km.

Amino Acid Transport Systems↗

Effects of oxygen on glucose-limited growth of Streptococcus mutans.

Aerotolerance in the growth of Streptococcus mutans and related streptococci was examined under glucose-limited conditions. The growth rate of all strains tested was more or less retarded when they were transferred from anaerobic to aerobic conditions. As for growth yield, however, some strains (group 1) showed reduced values for the increment of cellular dry weight change (in grams per mole of glucose), whereas others showed either unaltered (group 2) or increased (group 3) yields. The characteristic feature of strains in groups 2 and 3 was their high activity of both glucose- and pyruvate-dependent oxygen uptake when strains were grown under aerobic conditions. By contrast, the activity of pyruvate-dependent oxygen uptake by group 1 strains was negligibly low, whether grown under aerobic or anaerobic conditions. Some strains (group 1a) consumed oxygen in the presence of glucose at a much faster rate than others did (group 1b). There seems to be a good correspondence of these aerotolerance groupings to those based on serotypes of S. mutans. Thus, the groups 1a, 1b, 2, and 3 correspond to serotypes g, a+d, c+f, and b, respectively.

Aerobiosis↗

Recent morbidity trends in myocardial infarction in Japan: investigation of death certificates and the survival rates at coronary care units.

To elucidate recent trends in the mortality and morbidity of myocardial infarction (MI), we investigated death certificates and changes in the survival rate of MI patients at coronary care units (CCUs), which may affect the death rates. For all cases of MI, acute heart failure (AHF), heart failure (HF) as underlying cause, and hypertension as underlying cause with HF or AHF (categorized as hypertensive heart disease) on death certificates in two rural and two urban populations between 1981 and 1984, medical records were reviewed and case histories obtained from interviews with patients' families to validate the diagnosis. The number of MI deaths on the death certificates was not underestimated because some MI deaths were misdiagnosed as AHF, HF and hypertensive heart disease and some MI death certificates were misdiagnosed. Survival of MI patients at CCUs improved in several major cities, Tokyo, Osaka, Wakayama and Asahikawa between 1978 and 1984; a total of 4318 MI deaths were estimated to be averted by CCUs in 1984 compared with the number of deaths in 1978. Therefore, improvement of MI cases at CCUs may be one of the factors attenuating the rise in death rates in all of Japan.

Coronary Care Units↗

The trend of coronary heart disease and its risk factors based on epidemiological investigations.

Changes in the incidence of coronary heart disease (CHD) in the past 20 years have been observed in workers in the city and residents in rural areas and the risk factors of CHD studied. Findings show that the incidence of CHD in the residents in rural areas has hardly changed, and remains still low. However, the incidence of CHD in workers in the city has recently shown a tendency to increase. Furthermore, a study of CHD risk factors shows that in the rural areas residents hypertension has a strong influence on the incidence of CHD, while the role of serum total cholesterol is weak. In the city workers a high serum total cholesterol has become a risk factor. Therefore, it appears that the incidence of CHD caused by hypertension and by hypercholesterolemia are mixed in Japan. At present it appears that the influence of hypertension is becoming weaker, while the influence of hypercholesterolemia is becoming stronger. The resulting balance between them may be expressed as a rise and fall of CHD in Japan at present.

Adult↗