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Biomedical subjects

T Ashihara

Publications and source records attributed to T Ashihara.

At least 127 records · Page 7Linked to original sources

Plasma concentration of diltiazem after oral administration in normal volunteers.

The plasma concentration and hemodynamics of diltiazem after oral administration of 90 mg were studied in nine normal volunteers. Diltiazem was rapidly absorbed within three hours, and mean peak plasma concentration was 93.3 +/- 12.6 ng/ml (mean +/- SE). The plasma level gradually declined soon after, and almost no diltiazem was determined in 24-hours. Heart rate and blood pressure decreased slightly but significantly (P less than 0.001 and P less than 0.005, respectively). No prolongation of PR interval was demonstrated.

Administration, Oral↗

Granule formation in rat mast cells. Study with serial ultrathin sections.

The process of granule formation in mast cells was investigated with young mast cells in the milky spot of adult rats, seven days after an intraperitoneal injection of distilled water. Serial ultrathin sections were made and examined with an electron microscope to reveal the following results. The early step of granule formation is observed as a complex which consists of an irregularly shaped narrow vestibular space and several primary aggregate granules which are bowl-like in form, attached to the vestibular space and contain a few subgranules. The vestibular space has microvilli. The precursor materials seem to be secreted from the microvilli and transported through the vestibular space into the primary aggregate granules, being coagulated to become subgranules. As the subgranules increase in number, the primary aggregate granules become aggregate granules which grow further to their maximum size. With further addition of the materials, the aggregate granules become, through a step of ropy cord granule, mature dense homogeneous granules. The complex seems to remain as a unit after the maturation of granules and to react as a whole to any stimulus.

Animals↗

Constancy of the shift-up point in two temperature-sensitive mammalian cell lines that arrest in G1.

Two cell cycle-specific temperature sensitive (ts) mutants of mammalian cell lines, AF8 and K12, are known to arrest in G1 when shifted to the non-permissive temperature. We have determined the entry into S of both AF8 and K12 cells in five different growth conditions, namely: (1) quiescent sparse cultures stimulated to proliferative by serum; (2) quiescent dense cultures stimulated by serum; (3) quiescent sparse cultures stimulated by trypsinization and replating; (4) quiescent, dense cultures stimulated by trypsinization and replating; and (5) mitotic cells collected by mitotic detachment. In addition, for each cell line and for each different growth condition, we have determined the shift-up time, i.e., the time at which a shift-up to the nonpermissive temperature no longer prevents the entry of cells into S. In no case did K12 or AF8 enter S at the nonpermissive temperature. At the permissive temperature, the average time of entry into S varied in different growth conditions, and so did the shift-up time. However, in both cell lines, the distance of the average shift-up time from the average time of entry into S was remarkably constant, regardless of the growth conditions. i.e., 1.8 hours in K12 and 8.6 hours in AF8.

Cell Cycle↗

Characterization of ts13 cells a temperature-sensitive mutant of the G1 phase of the cell cycle.

ts 13 cells are a temperature-sensitive (ts) mutant of BHK cells that are known to arrest in G1 when shifted to the nonpermissive temperature. We have determined the entry into S of ts13 cells in five different growth conditions, namely: 1) quiescent, sparse cultures stimulated to proliferate by serum. 2) Quiescent, dense cultures stimulated by serum. 3) Quiescent, sparse cultures stimulated by trypsinization and replating. 4) Quiescent, dense cultures stimulated by trypsinization and replating. 5) Mitotic cells collected by mitotic detachment. For each different growth condition we have also determined the execution point of the mutant function, i.e. the time at which a shift-up to the nonpermissive temperature no longer prevents the entry of cells into S. The median time of entry into S and the execution point varied in different growth conditions, but the distance between the median execution point and the median time of entry into S was remarkably constant, i.e. 3.2 hr. In addition we have fused ts 13 cells cells with chick erythrocytes and studied the ability of ts13 cells in heterokaryon formation to induce DNA synthesis in chick nuclei. Although ts13 cells can induce DNA synthesis in chick nuclei at the permissive temperature, they fail to do so when fused and stimulated at the nonpermissive temperature of 39.5 degrees C.

Animals↗

A comparison of cell cycle-related changes in postmitotic and quiescent AF8 cells as measured by cytofluorometry after acridine orange staining.

AF8 cells were collected by mitotic detachment or made quiescent by serum restriction. Replated mitotic cells or serum-stimulated quiescent cells were then compared by flow cytofluorometry, when the use of acridine orange staining. Red fluorescence intensity (F greater than 600) was the same in quiescent cells and in cells immediately after mitosis. However, F greater than 600 increased very rapidly in postmitotic cells, while there was a delay in serum-stimulated quiescent cells. F greater than 600 reached a peak at 4 hr in postmitotic cells and between 16 and 19 hr in serum-stimulated quiescent cells. A similar delay in the time of entry into S phase occurred after serum stimulation of resting cell populations. The results are compatible with the hypothesis that cells after mitosis may enter a state that is different from the state of cells made quiescent by serum restriction.

Acridines↗

3H-Thymidine labeled mast cells in mice treated with 20-methylcholanthrene: proliferation of precursor cells, their transformation into mast cells and migration of the latter.

In an attempt to clarify the kinetics of increase of mast cells, autoradiographic studies were performed on the mice which received a painting of 20-methylcholanthrene on the skin. In the first experiment, mice received 20-methylcholanthrene painting on their back for two, four and eight weeks. A fourty-eight hours' cumulative labeling with 3H-thymidine was performed directly before sacrifice. No labeled mast cells were found in the painted skin, despite a marked increase of mast cells in number. In the second experiment, mice received 20-methylcholanthrene painting for thirty-one days. A twenty-four hours' cumulative labeling was performed three, five, seven, fourteen, twenty-one and thirty-one days before sacrifice. A high labeling index of mast cells, up to 61.29%, was obtained in each group. When the time lapse between the time of cumulative labeling and the sacrifice is long, the labeling index is higher in the subcutaneous tissue, and when the time lapse is short, the labeling index is higher in the subepidermal tissue. From these results it was concluded that; 1) An increase of mast cells is due predominantly to the proliferation of precursor cells and their transformation into mast cells. 2) The proliferation of precursor cells occurs mainly in the subepidermal layer of the skin. 3) After the transformation, mast cells may migrate into the deeper layer of the skin.

Administration, Topical↗

Analysis of incipient growth of Yoshida sarcoma in vivo after transplantation of a small number of tumor cells.

Incipient growth of Yoshida sarcoma in ascitic and solid forms was analyzed after transplantation of a small number of tumor cells varying from 1 to 10(6). Growth curves of the ascites tumors revealed that the duration of the incipient growth was much longer than the length of subsequent advanced stage and that the ascites tumor during its incipient stage appeared to grow exponentially and most rapidly in the entire course of the tumor development. Growth rate analyses of the ascites and solid tumors showed that, during their incipient stage, the population doubling time prolonged gradually as the inoculum size increased. This phenomenon was thought to suggest probable cell death on account of the transplantation procedure.

Animals↗

Endoscopic ultrasonography in the diagnosis of colorectal cancer invasion.

Endoscopic ultrasonography was pre-operatively performed in 164 patients with colorectal cancer, and the resected specimens confirmed to be cancerous histologically. Normal colorectal wall was visualized by endoscopic ultrasonography as a five-layered structure. The first, third, and fifth layers were hyperechoic, and the second and fourth layers were hypoechoic. The first and second layers comprised the mucosa, the third layer the submucosa, the fourth layer the muscularis propria, and the fifth layer the subserosa and serosa (adventitia). By this technique, cancer of the colon appeared as a hypoechoic mass with an intermediate echo level between the third hyperechoic and fourth hypoechoic layers. Endoscopic ultrasonographic determination of the depth of tumor invasion was based on abnormal changes of these layered structures and adjacent organs. Overall, the accuracy rate of endoscopic ultrasonography in the diagnosis of the depth of colorectal cancer was 83%. A hypoechoic round mass adjacent to the cancer was interpreted as a metastatic lymph node. The sensitivity and specificity of endoscopic ultrasonography in the diagnosis of lymph node metastasis were 68% and 70%, respectively. The overall accuracy rate of tumor staging by endoscopic ultrasonography according to Dukes' classification was 62%. Endoscopic ultrasonography is a valuable tool in the management of colorectal cancer. It has a high accuracy rate in determining the depth of tumor invasion. The pre-operative information obtained with this tool may influence the choice of therapy.

Colon↗

Effects of trapidil on forearm veins and arteries in man.

To understand the mechanisms of antianginal effects of trapidil, we examined the effects of trapidil, 100 mg i.v., on forearm veins and arteries in nine young healthy volunteers and compared the results with those of nitroglycerin, 0.3 mg s.1. At the doses used in the study, which are those in clinical use, trapidil and nitroglycerin increased forearm venous distensibility (p less than 0.05 for both) and decreased central venous pressure (CVP; p less than 0.01 for both). These results suggest that both drugs dilate veins. Forearm vascular resistance was decreased by trapidil but not by nitroglycerin. To examine the possibility that reflex vasoconstriction triggered by the decrease in CVP counteracted the direct vasodilator effect of the drugs, we studied the relationship between CVP and forearm vascular resistance while altering CVP by lower body negative pressure. Forearm vascular resistance at a comparable level of CVP was less after than before trapidil or nitroglycerin. These results suggest that both trapidil and nitroglycerin dilate forearm arteries in humans. Thus, we conclude that at a clinical dose, trapidil, as well as nitroglycerin, dilates forearm veins and arteries in humans.

Adult↗