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Biomedical subjects

T Shimamoto

Publications and source records attributed to T Shimamoto.

At least 199 records · Page 11Linked to original sources
PubMed1990

Effects of the physicochemical properties of the emulsion formulation on the bioavailability of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate in rats.

The effect of the physicochemical properties of the emulsion formulation on the absorption of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate (AL-294) in rats and dogs was studied. When emulsions of different particle sizes were administered to rats, the higher the ratio of Tween-80 to the drug was, the smaller was the particle size and the higher was the absorption. When the emulsions of similar particle size (2 microns) with different Tween-80 ratios were administered to rats, no significant difference was observed in the extent of absorption. The absorption of AL-294 was correlated with the dissolution rate from the oil phase to the aqueous phase but not correlated with the amount of AL-294 solubilized by Tween-80. These results indicate that the absorption of AL-294 from emulsions depends mainly on the particle size in the gastro-intestinal fluid and that Tween-80 serves only to reduce the particle size in the emulsion.

Animals↗
PubMed1990

Effects of physiological factors on the bioavailability of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate in an emulsion in rats.

The main absorption site of ethyl 2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionate (AL-294) in rats was the upper portion of the small intestine. Both AL-294 and AL-294 acid (2-chloro-3-[4-(2-methyl-2-phenylpropyloxy)phenyl]propionic acid), a hydrolyzed form of AL-294, were absorbed in a smaller quantity under the bile fistula condition (pancreatic juice and bile were excluded). Compared with the absorption of AL-294 as an emulsion under the sham operation condition, the absorption of AL-294 as the emulsion decreased under the condition where only pancreatic juice was excluded. The bioavailability under this condition was very similar to that under the bile fistula condition, whereas the absorption of AL-294 acid did not decrease when the pancreatic juice was excluded. From these results, the absorption mechanism of AL-294 is considered as follows: AL-294 was hydrolyzed to AL-294 acid by lipase in pancreatic juice, then AL-294 acid was solubilized with bile salts to form mixed micelles in the intestinal lumen. AL-294 acid from this form was easily absorbed into the systemic circulation. Absorption of AL-294 increased when the particle size of the emulsion was smaller. The reason was assumed to be that the smaller particle size offered the greater oil-water interface for lipase activity against AL-294.

Animals↗
PubMed1990

Trends for coronary heart disease and its risk factors in Japan: epidemiologic and pathologic studies.

Epidemiologic and pathologic studies were conducted between 1965 and 1986 to investigate trends for the incidence of coronary heart disease (CHD) and its risk factors in urban and rural populations and to relate the risk factor changes to trends for CHD incidence and pathologic findings. The epidemiologic study included men aged 40-59 years who urban residents of Osaka, clerical and manual workers in Osaka, and rural residents of Akita prefecture. The pathologic study subjects were autopsied men aged 30 and over, admitted to a local hospital in Akita, whose autopsy rate was 88%. From a cohort of 8,835 urban employees between 1975 and 1987, risk factors for myocardial infarction were identified: blood pressure, total serum cholesterol, blood glucose and cigarette smoking all which were compatible with findings in the US and European countries. For rural residents, serum cholesterol was less likely to be associated with the CHD incidence. Little contribution of serum cholesterol to development of coronary heart disease in rural men was supported by the pathologic study showing no significant association between serum cholesterol and the coronary atherosclerosis. Myocardial infarction from urban patients was characterized as massive necrosis in the myocardium with coronary artery stenosis and minimum atherosclerosis of basal cerebral arteries while that from rural men was small scattered necrosis in myocardium with atherosclerosis in both coronary and basal cerebral arteries. There was an increasing trend in the incidence of myocardial infarction in urban men but no change in rural men. The difference in the incidence trend can be attributed in part to differences in pathologic etiology and in blood pressure and serum cholesterol levels. Systematic surveillance is underway in both urban and rural population to clarify future trends for coronary heart disease and its risk factors.

Adult↗
PubMed1990

[Effects of oxygen on growth of Streptococcus mutans].

Effects of oxygen on growth of Streptococcus mutans Ingbritt (serotype c) were examined. The strain could be passaged under aerobic conditions at 37 degrees C in a peptone/yeast extract medium containing 0.2% glucose. Although the growth rate was slightly retarded under aerobic conditions (the doubling time, 60 min; 45 min under anaerobic conditions), the increment of cellular dry weight change was 35 g per mole of glucose under both conditions. To investigate such aerotolerance in growth as indicated by these results, oxygen metabolism was compared between aerobically and anaerobically grown cells. No difference was observed in the apparent rate of superoxide production or superoxide dismutation. However, aerobically grown cells showed a higher activity of hydrogen peroxide reduction with glucose as substrate and accumulated a lower level of hydrogen peroxide when incubated with glucose under aerobic conditions. In addition, hydrogen peroxide added to the medium was less inhibitory to anaerobic growth when aerobic cells were used as the inoculum. These results indicate that aerotolerance of S. mutans Ingbritt can be ascribed at least in part to its hydrogen peroxide reducing activity which is elevated under aerobic conditions.

Hydrogen Peroxide↗
PubMed1990

[Successful induction chemotherapy after colectomy in a case of acute lymphoblastic leukemia associated with obstructive ileus caused by sigmoid colon carcinoma].

We report here a patient who was diagnosed as having acute lymphoblastic leukemia (ALL-L2) and colon carcinoma simultaneously and a successful operation for the colon carcinoma was performed preceded to the treatment of ALL. The patient was a 43-year-old male who presented with acute abdominal symptoms and was diagnosed as ALL by the hematological examination and as colon carcinoma (well differentiated adenocarcinoma, Borrmann II) by colon fiberscope. The patient was underwent sigmoidcolectomy for colon carcinoma and was received antibiotics as well as recombinant human granulocyte colony-stimulating factor (rhG-CSF), Approximately two weeks later, the patient received AdVP (Adriamycin, vincristine, and prednisolone) for ALL and achieved a complete remission. It might be possible for some leukemia patients manifesting acute abdominal symptoms to perform surgical approaches, since the prognosis of leukemia patients improved and supportive therapies, including an application of rh-CSF, have developed.

Adenocarcinoma↗
PubMed1990

A case of rapidly growing gastric leiomyosarcoma: observations over 18 months.

A gastric leiomyosarcoma in a 68-yr-old female was followed for 18 months by serial roentgenography. On initial x-ray, the lesion was diagnosed as a benign submucosal tumor. However, it rapidly increased in size, with doubling time subsequently calculated as 5 months. After 18 months' periodic observation, a gastrectomy was performed for a suspected malignancy. Histologic examination of the resected tumor revealed a leiomyosarcoma originating in the muscular layer of the stomach. It appears that the poor prognosis of leiomyosarcoma is related to its rapid growth; in addition, it is seldom detected at an early stage. Follow-up of the patient with a gastric submucosal tumor should be done first, 6 months after the initial examination, and thereafter, be done continuously according to the patient's condition. It is useful in differentiating a benign from a malignant myogenic tumor.

Aged↗
PubMed1989

Serum fatty acids and fish intake in rural Japanese, urban Japanese, Japanese American and Caucasian American men.

To examine the relationship of fish intake with serum fatty acids cross-culturally, we surveyed a total of 136 men aged 34 to 55 years in four different populations: rural Japanese (RJ), urban Japanese (UJ), Japanese Americans (JA), and Caucasian Americans (CA). Mean levels of estimated total fish intake per day were 124.9 g in RJ, 70.8 g in UJ, 45.7 g in JA, and 32.3 g in CA. The percentage of total serum fatty acids contributed by omega-3 polyunsaturated fatty acids in these populations was 11.8% in RJ, 9.0% in UJ, 3.4% in JA and 2.5% in CA. Means of omega-3 fatty acids and intake of fish were correlated at the population level; this relationship was strongest when intake of dark-meat fish was considered (n = 4, r = 0.979, p = 0.02). Within each population, except for UJ, individual omega-3 fatty acid levels and dark-meat fish intake were significantly associated (p less than 0.05). A 20 g increase in dark-meat fish consumption was associated with an estimated relative increase in omega-3 fatty acid content of serum by 0.76% in RJ, 0.75% in UJ, 0.64% in JA, and 0.22% in CA. The association between fish intake and serum omega-3 fatty acids at the individual level was not explained by other coronary risk factors. Mortality from coronary heart disease is much lower in Japan than in the US. Population differences in fish intake and serum omega-3 fatty acid levels may contribute to the population difference in the risk of coronary heart disease.

Adult↗
PubMed1989

Hemostatic variables in Japanese and Caucasian men. Plasma fibrinogen, factor VIIc, factor VIIIc, and von Willebrand factor and their relations to cardiovascular disease risk factors.

Mortality rates of coronary heart disease are much lower and hemorrhagic stroke rates are higher in Japanese than in Caucasians. To investigate whether population differences in plasma concentrations of coagulation factors are consistent with these mortality differences, the authors examined, in 1987, a total of 136 men aged 34-55 years in four different samples: rural Japanese living in Akita, Japan; urban Japanese living in Osaka, Japan; and Japanese Americans and Caucasian Americans living in Minneapolis-St. Paul, Minnesota. The mean plasma fibrinogen level in Caucasians was 290 mg/dl, which was significantly higher than that in each of the Japanese samples (223-250 mg/dl; test for difference: p less than 0.001). The mean coagulation activities of factor VII and factor VIII (factor VIIc and factor VIIIc) were higher in Caucasian and Japanese Americans than in rural and urban Japanese (p less than 0.01 for factor VIIc and p = 0.03 for factor VIIIc). von Willebrand factor did not differ significantly across the populations. The relations of these coagulation factors with other cardiovascular risk factors (age, body mass index (weight (kg)/height (m)2), blood pressure, serum total cholesterol, serum triglyceride, cigarette smoking, and alcohol intake) were also examined. Mean plasma fibrinogen was consistently higher in current smokers than in nonsmokers within each sample. Factor VIIc and factor VIIIc levels were positively associated with serum total cholesterol and serum triglyceride. No consistent associations were seen between von Willebrand factor and cardiovascular risk factors. After the authors controlled for these covariates, mean fibrinogen and factor VIIc levels remained significantly different, but factor VIIIc levels did not. Different levels of coagulation factors across these samples are probably attributable to differences in environmental factors, especially diet, as well as genetic differences between Caucasians and Japanese. Furthermore, the differences in plasma fibrinogen and factor VIIc levels may explain part of the difference in mortality from cardiovascular disease across these populations.

Adult↗
PubMed1989

Purification and characterization of membrane-bound 5'-nucleotidase of Vibrio parahaemolyticus.

Membrane-bound 5'-nucleotidase from Vibrio parahaemolyticus was solubilized and purified using a nonionic detergent, heptyl-beta-D-thioglucoside, and was characterized. This enzyme required Mg2+ for activity, maximum activity being observed at 5 and 20 mM Mg2+ with AMP and ATP, respectively, as substrates. Of the divalent cations tested, Mn2+ and Co2+ were able to replace Mg2+ partially, whereas Ca2+ was ineffective. Zinc strongly inhibited the enzyme activity and Ni2+ caused partial inhibition. This enzyme required Cl- for activity, the optimal concentration being 20 mM or more. The order of effectiveness of anions was Cl- greater than Br- greater than I- approximately NO3-. Sulfate and acetate were ineffective. The optimal pH was 8.0. The activity of the purified enzyme was stimulated by the addition of lipid to the assay mixture. This enzyme hydrolyzed all 5'-nucleotides tested, but did not hydrolyze 3'-nucleotides or ribose 5-phosphate. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme appeared to be a single polypeptide, with a molecular weight of 72 kDa.

5'-Nucleotidase↗
PubMed1989

Cloning and expression of the 5'-nucleotidase gene of Vibrio parahaemolyticus in Escherichia coli and overproduction of the enzyme.

The gene encoding the membrane-bound 5'-nucleotidase of Vibrio parahaemolyticus was cloned and expressed in Escherichia coli. Cells of E. coli harboring a plasmid, pNUT5, which carries the 5'-nucleotidase gene were able to grow on ATP as the sole source of carbon, although the original cells were not. The 5'-nucleotidase activity was detected in whole cells of E. coli harboring pNUT5 and in membrane vesicles prepared from these cells. Most properties of the 5'-nucleotidase produced in E. coli, that is, its requirements for Cl- and Mg2+, substrate specificity, and inhibition by Zn2+, were similar to those observed in V. parahaemolyticus, but some alterations in properties were observed: The 5'-nucleotidase was partially inducible in V. parahaemolyticus, but its expression in E. coli was completely constitutive. The specific activity of the 5'-nucleotidase in membrane vesicles of E. coli harboring the plasmid was 30 times that observed in whole cells, whereas the specific activities in membrane vesicles and in whole cells of V. parahaemolyticus were almost the same. A new, dense band of protein with an apparent molecular mass of 63 kDa was detected when membrane proteins of E. coli harboring the plasmid were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

5'-Nucleotidase↗
PubMed1989

Controlled release of LHRH agonist, leuprolide acetate, from microcapsules: serum drug level profiles and pharmacological effects in animals.

The pharmacokinetic behaviour of leuprolide acetate from a controlled release parenteral dosage form has been studied in rats and dogs. The release of the drug in rats after a single subcutaneous injection exhibited pseudo-zero-order kinetics for one month in doses ranging from 0.0135 to 1.35 mg/rat; the release rate at a dose of 1.35 mg/rat was 2.8% of dose/day; after intramuscular injection the response was similar. In rats, the serum leuprolide acetate levels increased sharply immediately after injection by either route as a consequence of the initial release of the drug; subsequently, the levels attained a plateau for two weeks. The serum level profiles in dogs showed essentially the same pattern as those in rats. When the dosage form was injected into rats, the serum testosterone level (a pharmacological index) sharply peaked, abruptly decreased to below the normal level, and then was sustained at a suppressed level for over six weeks at a dose of 1.35 mg/rat (equivalent to 3 mg kg-1) and higher, while the serum testosterone level after an injection of 0.0135 and 0.135 mg/rat was not sufficiently suppressed. The profiles in dogs showed essentially the same pattern as those in rats. With multiple administrations (once every 4 weeks), serum testosterone levels in dogs did not show any sharp rise after the second and third injections. Changes in rat reproductive organ weights agreed well with the serum testosterone profile in the suppression. The results demonstrate that this dosage form releases the drug at a constant rate for one month and has a long-acting potency.

Animals↗
PubMed1989

Trends for coronary heart disease and stroke and their risk factors in Japan.

Disease surveillance and population surveys of risk characteristics in a northeast rural community of Japan (1965 census population, 7,030) are combined in an attempt to relate morbidity and risk factor trends for coronary heart disease and stroke during the last 2 decades. Between 1964 and 1983, the incidence of coronary heart disease (i.e., combined myocardial infarction, angina pectoris, and sudden death) did not change significantly among men and women ages 40-69, and was lower than that for stroke. The incidence of all stroke declined about 60% for both men and women, ages 40-69, with a significant decrease in cerebral hemorrhage for both sexes and in cerebral infarction for men. Between 1963-1966 and 1980-1983, significant upward shifts occurred in the means and distributions of serum total cholesterol and serum total protein in every age and sex group, primarily during the 1st decade. Age-adjusted mean cholesterol levels rose 22 mg/dl to the 1980-1983 mean of 179 mg/dl in men ages 40-69. In women ages 40-69, the mean rose 29 mg/dl to 192 mg/dl. Among nutrients, animal fat intake doubled in men ages 40-59 from 4.5% of daily calories in 1969 to 9.6% in 1980-1983. Animal protein intake also increased, from 5.8% to 7.1%. Most of this increase occurred between 1969 and 1972-1975 and may be attributable to an increased intake of meat, eggs and dairy products. From 1963-1966 to 1980-1983, mean relative weight index rose significantly for all age-sex groups except men ages 50-69. Mean systolic and diastolic blood pressure levels declined for every age-sex group, with a 15-mm Hg age-adjusted decrease in systolic, 4-mm Hg decrease in diastolic pressure among men ages 40-69, and a 11-mm Hg systolic and 4-mm Hg diastolic decrease for women. Two cohorts of men and women ages 40-69 at baseline were followed for disease incidence: an early cohort (2,257 persons) followed from 1963-1966 to 1973 and a later cohort (2,711 persons) followed from 1972-1975 to 1983. In these cohorts, significant risk prediction for cerebral hemorrhage and infarction was obtained with blood pressure level and end organ effects in the electrocardiogram and fundus photographs. Serum cholesterol was inversely associated with cerebral hemorrhage in the early cohort but not in the later.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Prediction of the virulencies of some enveloped viruses from the structure of the cleavage recognition site of viral glycoproteins essential for infectivity. I. Calculation of interaction energy.

Some evidences have been found that virulency in paramyxoviruses depends on the sensitivity of the cleavage recognition site of the F glycoprotein to serine type proteases. In this report, the interaction energies between the active site of trypsin and the cleavage recognition sites in paramyxoviruses are calculated. Results show that van der Waals energy and electrostatic energy contribute to the sensitivity. The virulencies of some myxo- and retro-viruses are then predicted on the basis of the two calculated interaction energy values.

Amino Acid Sequence↗
PubMed1989

[Clinical application of subrenal capsule assay in ovarian cancer].

The 6-day subrenal capsule assay (SRC) in normal immuno-competent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy and assess the usefulness of SRC in clinical application. A total of 18 different patients in 22 different assays were studied. Twenty-one assays (95%) were evaluable. The predictive sensitivity was 50%, the predictive resistance 75% and the predictive total accuracy 55% respectively. Sensitive drugs in repeated assays in four patients were not changed. Etoposide, cyclophosphamide, cis-platin and adriamycin were sensitive. Etoposide was the most sensitive of four drugs. The response rate was 50% in the patients treated with etoposide as the first line chemotherapy and the second line chemotherapy, respectively. Patients who were treated with sensitive drugs in SRC survived longer than the patients treated with cis-platin combined chemotherapy without etoposide. The median survival time was 19 months and the mean progression free interval was 15 months. In the results of this study, the value of SRC was supported by the results of chemosensitivity tests and etoposide seems useful in chemotherapy in ovarian cancer.

Adult↗
PubMed1988

Amino acid substitutions and alteration in cation specificity in the melibiose carrier of Escherichia coli.

We isolated mutants of Escherichia coli which showed Li+-resistant growth on melibiose. The melibiose carrier of the mutants lost the ability to couple to H+, whereas it retained the ability to couple to Na+. The mutated gene, melB, of the mutants was cloned, and the nucleotide sequence was determined. The nucleotide replacements caused the following substitutions of amino acid residues in the melibiose carrier: Pro-142 with Ser, Leu-232 with Phe, or Ala-236 with Thr or Val. These amino acid residues are located in slightly hydrophobic regions of the melibiose carrier. The results provide strong support for the idea that such regions or their vicinities which contain those amino acid residues play an important role in H+ (or Li+) recognition or H+ (or Li+) transport by the melibiose carrier.

Base Sequence↗