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Biomedical subjects

H Takenaka

Publications and source records attributed to H Takenaka.

At least 19 recordsLinked to original sources

Determination of tumor marker levels in cystic fluid of benign liver cysts.

The levels of tumor markers in cystic fluid and serum were measured in six patients with benign biliary cyst of the liver. AFP in the cystic fluid was lower than the upper normal limit for serum in all cases, and CEA in the cystic fluid was higher than the upper normal limit for serum in one of the six cases. CA19-9, DU-PAN 2, and SPAN 1 in cystic fluid were much higher than the upper normal limit for serum in all cases (more than 100-fold for CA19-9, twofold for DU-PAN 2, and ninefold for SPAN 1). CA19-9, DU-PAN 2, and SPAN 1 in cystic fluid were significantly higher than the levels in the corresponding serum. Positive immunohistochemical staining against CA19-9, DU-PAN 2, and SPAN 1 was observed in the cytoplasm of the epithelial cells of the cyst wall. These results suggested that the high concentrations of CA19-9, DU-PAN 2, and SPAN 1 in the cystic fluid were due to secretion from the epithelial cells in the benign biliary cysts.

Aged

[Cystic disease of right popliteal artery with spontaneous resolution].

The case was 50-year-old man. He was admitted to our hospital suffering from intermittent claudication. DSA and CT showed stenosis of the right popliteal artery due to compression by the tumor like lesion. The adventitial cystic disease was suggested. Three weeks later he had no symptom. DSA and CT revealed no reappearance of the adventitial cystic disease. The popliteal adventitial cyst spontaneously decreased in size. It is a very rare case.

Angiography, Digital Subtraction

Use of rabbits for GI drug absorption studies: relationship between dissolution rate and bioavailability of griseofulvin tablets.

The correlation between the dissolution rate and bioavailability of griseofulvin tablets was studied in stomach-emptying-controlled rabbits and in humans. Three different test tablets, each consisting of two dose levels (62.5 or 125 mg) of griseofulvin, were used. The dissolution rates in 0.5 hr were approximately 75, 40, and 12%. With oral administration at 62.5 mg/rabbit, the ratio of peak plasma level, Cmax, was 1.00:0.66:0.40 and that of the area under the curve (AUC) was 1.00:0.73:0.46 for the three tablets. The corresponding C'max ratio was 1.00:0.74:0.34 and the AUC ratio was 1.00:0.72:0.33 in humans at the dose level of 500 mg. A good correlation was observed for the rank order of Cmax and AUC between rabbits and humans, but such a correlation was not seen between in vivo data and in vitro data at a larger dose of 125 mg/rabbit. This finding was attributable to the dose, which exceeded the GI drug dissolution or absorption capacities. These results suggest that the stomach-emptying-controlled rabbit is useful for evaluating oral dosage forms for human use and that dose level selection is important in the bioavailability study of a barely water-soluble drug.

Administration, Oral

Functional implications of the two-headed structure of myosin.

This review summarizes the results obtained by biochemical and physiological studies on the functional implications of the two-headed structure of the myosin molecule. Our nonidentical two-head hypothesis of myosin is supported by biochemical studies on myosin ATPase. The reaction mechanism of the Mg2+-ATPase reaction catalyzed by one head of the myosin molecule is shown to be different from that catalyzed by the other head, and the reaction intermediate, MPADP, is produced in head B but not in head A. Evidence for differences in the chemical structures of the two heads of myosin is also presented. The myosin preparation is shown to be a mixture of homodimers with respect to its g-chain composition, but every homodimer has the non-identical two heads, B and A. Furthermore, the molecular mechanism for acceleration of the Mg2+-ATPase reaction by F-actin and that for its control by Ca2+ ions and Mg2+-ATP are discussed, based on the nonidentical two-head hypothesis of the myosin molecule. It was shown that the formation and decomposition of the key intermediate, A(B)MPADP are required for tension development and shortening. One cycle of ATP hydrolysis by crossbridges synchronously initiated by a rapid stretch or a sudden release of a slow stretch, indicating that the probability of dissociation of a crossbridge by its interaction with ATP depends on its angular position. It is also demonstrated that rotation of the base of nucleoside triphosphate about the glycosyl bond is essential for formation of MPXDP from M2XTP, as well as for muscle contraction. Based on these biochemical and physiological studies on the movement of the myosin head in muscle contraction, a molecular mechanism for muscle contraction is proposed.

Actomyosin

Interaction between actomyosin and 8-substituted ATP analogs.

Various 8-substituted ATP analogs were synthesized, and their reactions with myosin and actomyosin were studied. The nucleoside triphosphates (NTPs) with an amino group at the 6 position and hydrogen at the 8 position, and formycin 5'-triphosphate (FTP) were hydrolyzed by myosin very slowly in the presence of Mg2+ and rapidly in the presence of EDTA and K+. In contrast, NTPs with substitution of the 8 position, other than FTP, were readily hydrolyzed by myosin in the presence of Mg2+ but were hardly hydolyzed in the presence of EDTA and K+. The Michaelis constant (Km) for hydrolysis of 8-substituted NTP by heavy meromyosin was much larger than the dissociation constant (Kfl) for binding of heavy meromyosin with NTP estimated from the change in tryptophan fluorescence. All the NTPs with no substitution at the 8 position, and FTP, caused an initial Pi burst, actin activation of myosin NTPase, superprecipitation of actomyosin, and myofibrillar contraction. On the other hand, all the 8-substituted NTPs in three possible conformations did not cause these phenomena, regardless of the conformation. These results were discussed in relation to the hindrance of rotation about the glycosidic bond accompanying an 8 substitution.

Actomyosin

Use of rabbits for GI drug absorption studies.

A novel procedure to control the stomach emptying rate in rabbits is presented. Rabbits were given a special solid diet for 1 week, and then the gastric contents were washed out with saline. Then the rabbits were muzzled to prevent coprophagy during the night. Fifty grams of special soft diet given to the "stomach-emptying-controlled" rabbit transferred exponentially from the stomach into the small intestine and almost disappeared from the stomach within 5 hr. Griseofulvin, indomethacin, or nalidixic acid was administered in a hard gelatin capsule or tablet, with subsequent feeding of a special soft diet. Good correlations were observed between the plasma level-time curves of these drugs in the stomach-emptying-controlled rabbits and in human subjects.

Animals