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Biomedical subjects

T Oku

Publications and source records attributed to T Oku.

At least 199 records · Page 11Linked to original sources

Property and physiological role of biliary secretory IgA in rats.

Secretory IgA (sIgA) and monomeric IgA (mIgA) were purified from normal rat bile, and their role in the gastrointestinal tract was investigated. Biliary sIgA has a molecular weight of approximately 400,000 daltons and a sedimentation constant of 11.7S. Thus, sIgA obtained from rat bile had physicochemical properties similar to those reported for sIgA in other secretions, and probably consists of L-chains, alpha-chains and secretory component. After in vitro incubation with trypsin or intestinal fluid, sIgA remained intact, whereas mIgA was hydrolyzed. Rats challenged repeatedly with dinitrophenylated bovine serum albumin (DNP-BSA) had specific IgA antibody against DNP in the bile and feces as measured by a radioimmunoassay using [3H]-DNP-lysine. Our results demonstrate a possibility that biliary sIgA, not mIgA, has an important role which inhibits the absorption of foreign antigen from intestine.

Animals↗

Effects of interferon on C1300 mouse neuroblastoma.

The effects of murine interferon (MuIFN) with and without cyclophosphamide (CY) were evaluated in C1300 neuroblastoma-bearing mice. Mean survival times were prolonged by administration of 25,000 IU of MuIFN three times per week by ip injection. The combination of MuIFN and CY was more effective in the treatment of mouse neuroblastoma than either agent alone. Our results suggested that MuIFN is synergistic in combination with moderate amounts of CY in mouse neuroblastoma cells and may be given for the treatment of neuroblastoma.

Animals↗

Different susceptibilities of cultured mouse cell lines to mouse interferon.

Cultured mouse cells were treated with 3.3 approximately 10,000 units of mouse interferononon for 3 days and further cultivated in fresh medium for 2 days (recovery incubation). The IC50 (concentration of drug required for 50% inhibition) of interferon was not changed much after the recovery incubation. The most susceptible cell line to interferon was B16 melanoma; the IC50 was 10.5 units per ml of medium on day 3 after the start of treatment. P388 leukemic cells, Lewis lung carcinoma cells, and colon adenocarcinoma 38 cells were moderately susceptible to interferon and the IC50s of these cell lines were 200, 80, and 180 units per ml medium, respectively, on day 3. The cells least susceptible to interferon were those of colon adenocarcinoma 26; IC50 was greater than 10,000 units per ml. In the recovery incubation, the growth of B16 melanoma cells, P388 leukemic cells, Lewis lung carcinoma cells and colon adenocarcinoma 38 cells was considerably inhibited when these cells were treated with more than 100 approximately, 1,000 units of interferon per ml medium. The rate of multiplication was usually more than 1 for these cell lines, except for Lewis lung carcinoma cells where the rate of multiplication was less than 1. This indicates that interferon is not cytocidal towards B16 melanoma cells, P388 leukemic cells, or colon adenocarcinoma 38 cells, but mouse interfer is cytocidal towards Lewis lung carcinoma cells when the cells are treated with a relatively high concentration of interferon and then cultured in the medium without interferon.

Adenocarcinoma↗

Assessment of anti-tumor cell effect of human leukocyte interferon in combination with anticancer agents by a convenient assay system in monolayer cell culture.

Cell growth inhibition by anticancer agents was determined by a simple dye-uptake method. This technique could be performed more easily and rapidly than the cell counting method, the method for measurement of 3H-thymidine incorporation, or other dye-uptake methods. The number of viable cells was linearly correlated with the amount of dye taken by the surviving cells, so that the method described in this article could be applied to the assessment of anti-tumor cell effects of human leukocyte interferon (Hu IFN-alpha) in combination with anticancer agents. In combinations of Hu IFN-alpha with anticancer agents such as bleomycin, mitomycin C, and cytosine arabinoside in certain concentration ranges, antagonism was noticed when Hu IFN-alpha and anticancer agents were added simultaneously to the cell culture. However, outside those ranges of concentration, additive effects were observed. Furthermore, the treatment of the cell with IFN followed by the anticancer agents and vice versa showed additive effects.

Antibiotics, Antineoplastic↗

Induction of pulmonary indoleamine 2,3-dioxygenase by interferon.

Pulmonary indoleamine 2,3-dioxygenase [indoleamine: oxygen 2,3-oxidoreductase(decyclizing)] has been found to be induced (30- to 100-fold) in the mouse after a single intraperitoneal administration of bacterial endotoxin [Yoshida, R. & Hayaishi, O. (1978) Proc. Natl. Acad. Sci. USA 75, 3998-4000] or during in vivo virus infection [Yoshida, R., Urade, Y., Tokuda M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. In the present study, an in vitro system with mouse lung slices was developed in which bacterial endotoxin (5 micrograms/ml)produced an induction (approximately 10-fold) of indoleamine 2,3-dioxygenase. The endotoxin was substituted by interferon from mouse L cells or mouse brain. The pulmonary enzyme activity increased almost linearly for 48 hr after addition of mouse interferon (10(4) units/ml) to lung slices. Interferon from mouse L cells or mouse brain produced a 10- to 15-fold increase in the enzyme activity, whereas that from human leukocytes was all but ineffective. The effect also was observed using highly purified L-cell interferon, prepared by poly(U) affinity column chromatography. When interferon was treated either by heat, alpha-chymotrypsin, or anti-interferon serum, such increase in the enzyme activity was diminished essentially to the same extent as seen in the antiviral activity. The increase in the enzyme activity was blocked when actinomycin D or cycloheximide was added to the slices before interferon treatment. These results suggest that the enzyme induction was produced by interferon and not by possible contaminants in the interferon preparations.

Animals↗

Inhibition of interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung by inhibitors of prostaglandin biosynthesis.

Inhibitors of fatty acid cyclooxygenase such as indomethacin (0.1 mM), phenylbutazone (0.3 mM), and aspirin (1 mM) were found to suppress almost completely the interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung slices. However, phenacetin, an anti-inflammatory agent devoid of cyclooxygenase inhibitory activity, and sodium salicylate, a weak inhibitor of cyclooxygenase, were much less active under identical conditions. Glucocorticoids including dexamethasone, betamethasone, and cortisone, all of which are inhibitors of phospholipase A2, blocked induction of the dioxygenase by interferon in the nanomolar range, whereas other steroid hormones, such as aldosterone, testosterone, and 17 beta-estradiol, were all but ineffective. These results suggest that the enzymes phospholipase A2 and fatty acid cyclooxygenase, both of which are essential for the biosynthesis of prostaglandins, play an important role in the induction of indoleamine 2,3-dioxygenase by interferon.

Animals↗

A new aspect on the mechanism of intestinal cholesterol absorption in rat.

In order to study the mechanism of intestinal cholesterol absorption, the relationship between the amount of cholesterol administered and the rate of absorption was investigated by the dual isotope plasma ratio method in vivo and the ligated-loop method in situ. The energy requirement of cholesterol absorption was also observed by means of the ligated-loop method. The results obtained are summarized below. 1) Tri-phase absorption was observed by the dual isotope plasma ratio method. When less than 300 microgram of cholesterol was administered, absorption increased linearly, with the coefficient of absorption being more than 80%. When the amount administered was between 300 and 500 microgram, the absorption was constant. With the administration of more than 500 microgram, absorption increased linearly, but the coefficient of absorption decreased to approximately 55%. 2) With the ligated-loop method, a second saturation profile was obtained when between 250 and 400 microgram of cholesterol was administered to a segment. When 50 to 250 microgram of cholesterol were administered, absorption increased in proportion to the increase in cholesterol dosage. 3) The mucosal uptake of cholesterol decreased to 40-60% of the control with the addition of metabolic inhibitors such as NaN3, KCN, 2,4-DNP and ouabain, whereas the uptake of palmitate showed no significant decrease. In addition, the uptake of cholesterol decreased remarkably to 25% of the control with the lowering of body temperature from 37 degrees C to 27 C. These results suggest the existence of an active transport system which has a limited capacity for cholesterol absorption and which requires energy for its operation in the physiological state.

Animals↗

New simple dye-uptake assay for interferon.

Using the spectrophotometer that the authors developed, the amounts of human leukocyte and mouse L cell interferons on FL cells and L929 cells were measured and values were compared with those measured by the cytopathogenic effect (CPE) reduction method (CPE method). The spectrophotometric method, which was simpler than the original dye-uptake method, was found to be more sensitive than the latter. When Sindbis virus was used instead of vesicular stomatitis virus (VSV), there were no significant differences in the sensitivities of the two methods or the interferon titers estimated. When FL cells or L929 cells were treated with interferon at the time of their dispersion, their interferon titers were almost the same as those of cells treated with interferon 2 days after dispersion. It is concluded that this new dye-uptake method is useful for assay of human and mouse interferons.

Biological Assay↗

Pancreatic cancer with metastasis to the larynx.

A laryngeal metastasis from pleomorphic carcinoma of the pancreas is described. The patient was a 70-year-old male. The tumour was located on the right margin of the epiglottis. Bilateral neck lymph node metastases were also found. The patient underwent supraglottic laryngectomy, right radical neck dissection and left suprahyoid neck dissection. Following surgery, the patient's general condition deteriorated day by day, and one month after the surgery he died. The autopsy findings demonstrated a big mass of cancer in the pancreatic tail, multiple lymphatic metastases, carcinomatous peritonitis, and possibly a lymphatic spread of the pancreatic cancer to the larynx.

Aged↗