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Biomedical subjects

F Okada

Publications and source records attributed to F Okada.

At least 109 records · Page 6Linked to original sources
PubMed1990

Regression mechanisms of mouse fibrosarcoma cells after in vitro exposure to quercetin: diminution of tumorigenicity with a corresponding decrease in the production of prostaglandin E2.

We have previously reported that both regressor (QR) and progressor (metastatic, QP) clones were obtained after the in vitro exposure of a mouse fibrosarcoma BMT-11 cl-9 to quercetin. In this study, we investigated possible mechanisms of spontaneous regression of QR clones as compared with tumorigenic QP and BMT-11 cl-9 tumor clones. We observed that BMT-11 cl-9 cells produced relatively high amounts of prostaglandin E2 (PGE2) during in vitro culture. The average production by 11 subclones of BMT-11 cl-9 cells was 9236 +/- 2829 pg/ml whereas that by 9 QR clones was 3411 +/- 2213 pg/ml (P less than 0.02). Indomethacin not only inhibited in vitro PGE2 synthesis by QP clones (high-PGE2 producers) but also the s.c. growth of QP clones in mice. Chronological changes in host immune responses to tumor-associated antigen were measured by cytotoxic T lymphocyte (CTL) activity examined after mixed lymphocyte/tumor cell culture of spleen cells obtained from tumor-bearing mice. The CTL activity disappeared abruptly in the spleen of QP-clone-bearing mice 21 days after the inoculation of tumors, whereas the spleen cells of QR-clone-inoculated mice retained their CTL activity. We determined that the mechanism responsible for the regression of these regressor clones is not due to any qualitative or quantitative increase in pre-existing membrane antigens, nor the emergence of new antigen(s) on the cell surface of the QR clones: nor was it due to enhanced susceptibility of QR clones to natural killer cells, lymphokine-activated killer cells and macrophages. These finding suggest that the regression mechanism of QR clones may be the diminished inhibition of host response to tumor-associated antigen caused by the reduced production of PGE2 by QR clones.

Animals↗
PubMed1990

Psychiatric aspects of acute pandysautonomia.

Five cases of acute pandysautonomia and one case of acute autonomic and sensory neuropathy are described with special reference to psychiatric symptoms. They originally presented as psychiatric disorders, such as hysterical neurosis, epilepsy, anorexia nervosa and hypochondriacal neurosis. Psychiatric symptoms arise from their autonomic nervous dysfunction and show emotional instabilities which are often regarded as hysterical overacting.

Acute Disease↗
PubMed1990

Molecular cloning of the large subunit of transforming growth factor type beta masking protein and expression of the mRNA in various rat tissues.

Masking protein (MP), which neutralizes the activity of transforming growth factor type beta 1 (TGF-beta 1), is composed of a dimeric N-terminal part of a TGF-beta 1 precursor of Mr 39,000 and an unknown large subunit of Mr 105,000-120,000. The deduced primary structure of the MP large subunit was elucidated by determining the nucleotide sequence of its cDNA. The cDNA encodes a prepro-precursor of 1712 amino acid residues with a calculated Mr of 186,596. The mature large subunit seems to be derived proteolytically from a prepro-precursor and the calculated Mr is 91,606. The precursor has seven N-linked glycosylation sites and an unusual structure containing 18 epidermal growth factor-like domains and four cysteine-rich internal repeats. The large subunit mRNA is synthesized in parallel with the expression of TGF-beta 1 mRNA in various rat tissues.

Amino Acid Sequence↗
PubMed1990

Correlation between the presence of microvilli and the growth or metastatic potential of tumor cells.

We used an electron microscope to examine microvilli which appear on the surfaces of various tumor cells with high or low growth potential and/or metastatic ability. The results show that a greater number of microvilli appeared on the surfaces of tumor cells (QRpP and ERpP) which possess high growth potential than on tumor cells (QR and ER) with low growth potential. We also observed that microvilli were more abundant on the surface of highly metastatic clone cells, i.e. c-SST-2 (cl-2), mouse B16 melanoma (F-10) and human colon carcinoma (KM12SM) than on weakly metastatic clone cells, c-SST-2 (cl-4-2), B16 (F-1) and (KM12C). At the same time, more microvilli were observed on the surface of B16 BL6 cells, which were obtained from the metastatic site of the B16 F10 cells, than on the surface of the parent B16 F10 cells. Immunoelectron microscopy revealed that the c-neu oncogene product, which is closely related to an epidermal growth factor receptor, was positively stained in the microvilli of tumor cells (ERpP) with high growth potential and high metastatic ability, whereas the tumor cells (ER) with low growth potential and weak metastatic ability were not stained. These findings suggest that the increased presence of microvilli correlates closely with the growth potential and metastatic ability of tumor cells.

Animals↗
PubMed1990

[Novel phenoxyalkylamine derivatives. VI. Synthesis and alpha-blocking activity of alpha-[(phenoxyethylamino)propyl]-alpha-phenylacetonitrile derivatives].

alpha-[(Phenoxyethylamino)propyl]-alpha-(4-methoxyphenyl) acetonitrile derivatives possessing methyl, bromo, nitro, amino or various sulfonamide groups at 3-position on ring A and an alkoxy group on ring B were synthesized. Their alpha-blocking activities were tested. The activity of 5-[1-cyano-4-[[2-(2-ethoxyphenoxy) ethyl]amino]-1-isopropylbutyl]-2-methoxy-benzenesulfonamide (15a) and 5-[1-cyano-4-[[2-(5-fluoro-2-methoxyphenoxy)ethyl] amino]-1-isopropylbutyl]-2-methoxybenzenesulfonamide (15c) was close to that of prazosin, a typical alpha-blocker. Structure-activity relationship of these derivatives is also stated.

Acetonitriles↗
PubMed1990

[Progression of regressor tumor cells by host reactive cells to such foreign bodies as plastic plate and hemostatic spongel].

I examined the effects of host cells reactive to foreign bodies such as plastic plate or hemostatic spongel on the progression of tumor cells. QR tumor cells spontaneously regressed in normal C57BL/6 mice apparently associated with a reduction in production of PGE2 by the tumor cells. I have observed that such regressor tumor cells are able to grow lethally when implanted in mice after having been attached to plastic plate. The clones which were derived from these plastic plate-derived tumors in normal mice maintained their growth potential when they were injected into other normal mice. Furthermore the arising tumors produce much higher levels of PGE2 than the original QR tumor cells. Interestingly, I could not observe acquisition of tumorigenicity or a higher level of PGE2-production in the clones obtained from the arising tumors which were grown in 10Gy-irradiated mice. Moreover, QR tumor cells are able to grow in mice when they are injected at the site where plastic plate had been implanted about 30 days previously. These results indicate that the restoration of tumorigenicity of QR tumor cells is not only due to attachment to plastic plate, but also mediated by radiation-sensitive host cells reactive to plastic plate which enhance the progression of tumor cells. Similar results are also obtained by coinoculation of QR tumor cells with host reactive cells which had been induced by implantation of hemostatic spongels into the peritoneal cavity of mice. Greater amounts of PGE2-production by QR tumor cells were observed when the tumor cells were cocultured with spongel reactive cells. This PGE2-production was markedly inhibited by the presence of radical scavengers (Catalase, Mannitol, SOD + Catalase) in the coculture medium(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

One of two subunits of masking protein in latent TGF-beta is a part of pro-TGF-beta.

A high molecular mass latent form of transforming growth factor type-beta (TGF-beta) was purified to homogeneity from rat platelets by a seven-step procedure involving group-specific affinity chromatographies on Red-Toyopearl and zinc chelating-Sepharose. The purified latent TGF-beta was a complex of TGF-beta (25 kDa) and the binding protein previously named masking protein (approximately 400 kDa) [(1986) Biochem. Biophys. Res. Commun. 141, 176-184]. Analysis of the peptide structure by gel electrophoresis showed that the masking protein consisted of two subunits of 39 kDa and 105-120 kDa linked by disulfide bonds. N-terminal amino-acid sequencing of the 39 kDa subunit indicated that this subunit was identical to the N-terminal part of the TGF-beta precursor.

Amino Acid Sequence↗
PubMed1989

Primary neurilemoma of the diaphragm.

A neurilemoma of the diaphragm in an asymptomatic 46-year-old woman is reported, and 12 cases of primary neural tumor of the diaphragm reported previously are reviewed. The common symptoms in these patients are chest pain, cough, and dyspnea. Joint pain or clubbing of the fingers is present in nearly half of the patients. As with diaphragmatic tumors in general, many neural tumors of the diaphragm are malignant. We believe that all such tumors should be resected through a thoracotomy incision, which affords optimal exposure of the diaphragm.

Diaphragm↗
PubMed1989

Inhibition of mitomycin C-induced sister-chromatid exchanges in mouse bone marrow cells by the immunopotentiators Krestin and Lentinan.

We have carried out an investigation to determine whether or not the sister-chromatid exchange frequencies (SCEs) observed in bone marrow cells in mice treated with mitomycin C (MMC) are inhibited by the immunopotentiators Krestin and Lentinan. We found that mitomycin C (2 mg/kg, i.v.)-induced SCEs were inhibited in 27% of the mice treated with Krestin (300 mg/kg, i.p.) and in 23% of the mice treated with Lentinan (1 mg/kg, i.p.). The effects of Krestin were found to be dose-dependent in inhibition of MMC-induced SCEs while those of Lentinan were not. Our findings therefore suggest that Krestin and Lentinan are not only useful for cancer treatment as immunopotentiators in combination with anticancer drugs but may also prevent the increase of chromosomal damage induced by anticancer drugs.

Adjuvants, Immunologic↗
PubMed1989

Purification and structural analysis of a latent form of transforming growth factor-beta from rat platelets.

A latent form of transforming growth factor type-beta (TGF-beta) with a high molecular weight was purified to homogeneity from rat platelets by a six-step procedure. The yield of the purified latent TGF-beta from platelets of 2,500 rats was 1.4 mg. The purified latent TGF-beta was activated by treatment with urea at concentrations of over 4M or acidic solutions of below pH 4. SDS-PAGE and gel filtration chromatography showed that the latent TGF-beta consisted of active TGF-beta and glycoproteins of about 200 kDa as masking components, and that under physiological conditions, these components formed a high molecular weight complex of about 400 kDa linked by non-covalent bonds. Here, we found that the masking protein was composed of one large subunit of about 110 kDa and two small subunits of 39 kDa linked by disulfide bridges. The N-terminal amino acid sequence of the small subunit was identical to the N-terminal region of the TGF-beta precursor lacking a signal peptide. From these findings, we proposed a structural model for the latent TGF-beta from rat platelets.

Amino Acid Sequence↗
PubMed1989

Pertussis toxin attenuates 5-hydroxytryptamine1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes.

The inhibition of forskolin-stimulated adenylate cyclase activity by 5-hydroxytryptamine (5-HT) receptor agonists was measured in rat hippocampal membranes isolated from animals treated with vehicle or islet-activating protein (IAP; pertussis toxin). In vehicle-treated animals, 5-HT, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and gepirone were potent in inhibiting forskolin-stimulated adenylate cyclase activity with EC50 values of 60, 76, 376, and 530 nM, respectively. IAP treatment reduced by 30-55% the 5-HT1A agonist inhibition of adenylate cyclase activity via 5-HT1A receptors. The data indicate that the inhibitory guanine nucleotide-binding protein or Go (a similar GTP-binding protein of unknown function purified from brain) mediates the 5-HT1A agonist inhibition of hippocampal adenylate cyclase.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Two cases of Hashimoto's thyroiditis with pupillary disturbances.

Two cases of Hashimoto's thyroiditis with pupillary disturbances are reported. Case 1 was a 58-year-old housewife, displaying pandysautonomia. Case 2 was a 65-year-old housewife, suffering from chronic polyneuropathy and polymyopathy. Both patients showed similar pupillary disturbances, suggesting both sympathetic and parasympathetic postganglionic denervation of the pupil. Hashimoto's thyroiditis may have caused the pupillary disturbances in association with generalized polyneuropathy or pandysautonomia.

Aged↗
PubMed1989

[Acute pandysautonomia and acute autonomic and sensory neuropathy].

Acute pandysautonomia and acute autonomic and sensory neuropathy were reviewed with special reference to their clinical entity, pathogenesis and clinical course. Since acute pandysautonomia was primarily described as an entity by Young et al. in 1969, a number of similar cases have been described. The disorder is characterized by severe sympathetic and parasympathetic impairment with relative or complete preservation of somatic motor and sensory functions. Some cases have only shown a cholinergic dysautonomia, while others have displayed a loss of autonomic function together with other impairments of nervous function. In 1980, Colan et al. reported a patient with acute autonomic and sensory neuropathy, manifesting severe sensory impairment and dysautonomia with marked loss of myelinated and unmyelinated fibers. Several other similar cases have appeared in the literature. Four years prior to the Colan et al. report, the author described a case which showed almost the same symptoms. At the present time, it is not clear whether this disorder is a new syndrome that is different from acute pandysautonomia or merely a subtype of it. The causes of the above two syndromes are unknown; however, an immunological disorder similar to the Guillain-Barré syndrome has been suggested. The clinical course is often protracted with slow improvement. However, from the author's experience, a relatively rapid improvement occurs after a single systemic administration of either parasympathomimetic or sympathomimetic agonists. Acute pandysautonomia which includes acute autonomic and sensory neuropathy has recently become more common: A number of similar cases have been reported worldwide, including many areas in Japan.

Acute Disease↗
PubMed1989

[Experimental approach to the investigation of tumor progression].

We investigated the effects of host inflammatory cells on the progression of QR (C57BL/6 mouse) and ER (SHR rat) regressor tumor cells which spontaneously regress in normal syngeneic hosts. We noted an enhanced tumorigenicity of regressor tumor cells after s.c. implantation with attachment to plastic plate, a situation which induces inflammation in normal hosts accompanied by the development of tumors as compared to normal mice injected with regressor tumor cells in suspension in PBS- which spontaneously regressed. We also observed enhanced tumorigenicity of regressor tumor cells injected into the site of the plastic plate which had been previously implanted into the normal host. Regarding these phenomena, we suggest that tumor progression may be induced by host induced inflammatory cells or their products. We also found enhanced tumor progression of QR regressor tumor cells after co-inoculation with inflammatory cells produced by the implantation of hemostatic spongel into the peritoneal cavity of mice. The mechanisms involved in the progression of regressor tumor cells by co-existence with inflammatory cells are thought to be associated with the production of oxygen radicals, tumor cell chemotactic factors, soft agar colony promoting factors and PGE2.

Animals↗
PubMed1988

Improved therapeutic effects of interleukin 2 after the accumulation of lymphokine-activated killer cells in tumor tissue of mice previously treated with cyclophosphamide.

We investigated the combined effects of human recombinant interleukin 2 (IL-2) and cyclophosphamide (CY) on s.c. transplanted 3LL lung carcinoma in C57BL/6 mice. A total of 95% of the tumors were completely cured when CY (150 mg/kg, i.v.) was given on day 5 (5 days after tumor implantation) and IL-2 (5 x 10(4) Jurkat Units/day, i.p.) was then combined with it between day 6 and day 15. CY alone brought about the complete regression of tumors, although 60% of the mice died of local recurrence and pulmonary metastasis; IL-2 alone had no therapeutic effect. Satisfactory effects from the combination of CY and IL-2 were also obtained by 5 days administration of IL-2 between days 11 and 15, initiated 6 days after CY treatment, but not by that given before CY (days 1-5) or 1 day after CY (days 6-10). No therapeutic effects from IL-2 were observed when it was combined with other types of chemotherapy that showed not therapeutic effects by themselves. Nor were we able to observe any transplantation resistance to the rechallenge of 3LL tumor in cured mice. We particularly examined the lymphokine-activated killer (LAK) cells as we suspected that these were responsible for the development of active effector cells in the treated mice. LAK cell activity in fresh spleen cells was detected in mice treated with IL-2 alone but not in untreated mice nor in those treated with CY alone or CY plus IL-2. The number of LAK precursor cells in the spleen had increased on day 8 and on day 13 in untreated mice with 3LL, as compared with the incidence in normal mice, while the number of cells had decreased by day 18. On the other hand LAK precursor cells were suppressed on day 8 and tended to recover thereafter in CY-treated mice. Adoptively transferred LAK cells were found to accumulate in CY-treated tumors 2.5 times more densely than in untreated tumors. The preferential accumulation of LAK cells that had been activated systemically by the appropriately timed administration of IL-2 in tumor tissue was followed by the improved effects obtained by combined treatment with CY and IL-2.

Animals↗
PubMed1988

Effects of a combination of cyclophosphamide and human recombinant interleukin 2 on pulmonary metastasis after the surgical removal of a 3-methylcholanthrene-induced primary tumor in autochthonous mice.

We have investigated the therapeutic effects of a combination of cyclophosphamide (CY, 150 mg/kg, iv) and human recombinant interleukin 2 (IL-2, 5 x 10(4) JU/day, ip for 5 days) on autochthonous tumors induced in mice by 3-methylcholanthrene. The initial treatment was carried out when the tumor had reached 8 to 10 mm in diameter. Twenty-eight out of 35 mice (80%) died of local recurrence and pulmonary metastasis of tumor cells within 53 +/- 40 days (mean survival time, MST +/- SD) after the surgical removal of the primary tumor. When these mice were treated with both CY and IL-2 following the operation (Op), only 10 out of 20 mice (50%) died of recurrence and metastasis. The survival rate, however, was not improved by CY chemotherapy alone or IL-2 immunotherapy alone, although each provided a prolongation of the MST. Natural killer cell and LAK precursor cell activities in the spleen cells from the treated mice were found to be restored by IL-2 alone or CY + IL-2, whereas they were suppressed by CY alone. These findings reveal that the restoration of the antitumor activity of spleen cells does not provide an improved therapeutic effect by itself and that IL-2 immunotherapy requires the associated effect of CY chemotherapy to achieve an improved therapeutic effect.

Animals↗
PubMed1988

Possible involvement of pertussis toxin substrates (Gi, Go) in desipramine-induced refractoriness of adenylate cyclase in cerebral cortices of rats.

To evaluate the efficiency of coupling between beta-receptor and adenylate cyclase catalyst via a GTP-binding protein, Gs, in the brain membrane two parameters were employed: a beta-agonist-induced increase in the membrane GTP-dependent adenylate cyclase activity and a beta-agonist-induced shortening of the lag time preceding the onset of the steady-state activation by guanyl-5'-yl-beta-gamma-imidodiphosphate [Gpp(NH)p] of the membrane cyclase. Both parameters showed lower values in membranes from desipramine-treated rats compared with untreated rats. Thus, coupling of beta-adrenergic receptors to adenylate cyclase in the brain membrane was impaired by the desipramine treatment. Rats once injected intraventricularly with islet-activating protein (IAP), pertussis toxin, were subjected to desipramine treatment, for the purpose of studying effects of another kind of the GTP-binding protein (Gi), which loses its function as a signal transducer on being ADP-ribosylated selectively by the toxin. IAP treatment did not impair the beta-receptor coupling by itself, since neither of the above two parameters for the coupling were reduced by IAP treatment. Moreover, the first parameter was normalized, though the second one was not, by superimposition of the IAP treatment upon the desipramine-treated rats. It seems likely, therefore, that Gi interacts with a Gs-adenylate cyclase coupling in an inhibitory fashion in brain membranes. The desensitization might be overcome when the inhibitory interaction of Gi on the subsequent process is attenuated by IAP treatment.

Adenosine Diphosphate Ribose↗