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T Tokunaga

Publications and source records attributed to T Tokunaga.

At least 235 records · Page 13Linked to original sources
PubMed1986

In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG.

A fraction extracted from BCG and designated MY-1, which was composed of 70.0% DNA and 28.0% RNA, was previously reported to possess strong antitumor activities against various syngeneic mouse and guinea pig tumors. An intraperitoneal injection of MY-1 (100 micrograms) 1 day before rendered mouse peritoneal cells cytotoxic to YAC-1 cells. The effector cells were nonadherent to plastic dishes, and the activity was destroyed by treatment with anti-asialo GM1 antiserum plus complement or carrageenan in vitro, but not with carbonyl-iron or anti-Thy 1.2, suggesting that the cells are natural killer (NK) cells. In vivo augmentation of NK activity was dependent on MY-1 dose, and reached the peak 1 day after MY-1 injection. Since NK activity in lipopolysaccharide (LPS)-nonresponder mice could be augmented by MY-1, the possibility that LPS contaminated the MY-1-augmented NK was excluded. MY-1 digested preliminarily with DNase lost its NK-inducing activity, suggesting that the DNA entity of MY-1 was essential for the activity. When mice were pretreated with anti-asialo GM1 or carrageenan, MY-1 could not render the peritoneal cells cytotoxic. Antitumor activities of MY-1 were also abolished if the animals were pretreated with anti-asialo GM1 antiserum or carrageenan, suggesting that the activities can be ascribed mainly to activated NK cells.

Animals↗
PubMed1986

[T cell leukemia antigens, FT-1 and FT-2].

The understanding of the differentiation process of lymphocytes in the embryonic thymus has been based on extrapolation from adult thymic lymphocytes. The study presented here was mainly concerned with the new cell surface antigens designated FT (FT-1, FT-2), which are expressed on fetal thymocytes of all mouse strains examined, but not on thymocytes or any other lymphoid cells of adult mice. One of the interesting features of FT antigens is the timing of their expression in connection with the ontogeny of thymic lymphocytes. A majority of fetal thymocytes at the 13th day of gestation express FT antigens, whereas no positive cells are found in fetal liver. Therefore, FT antigens seem to appear as soon as the stem cells have reached the thymus. The proportion of FT+ cells then declines sharply with increase in the time of gestation, while Thy-1+ cells increase in inverse proportion. All of these results seem to support the idea that the thymocytes expressing FT antigens are replaced with Thy-1+ thymocytes, although the possibility of the transition from FT+ to Thy-1+ cells cannot be excluded. It was also demonstrated that fetal thymocytes are heterogeneous with respect to the expression of FT-1 and FT-2 antigens. Especially, thymic lymphocytes at the earlier stages of ontogeny can be divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-. With the emergence of Lyt antigens, these subpopulations seem to differentiate and acquire far more complicated features. Such cellular heterogeneity probably reflects the complexed events like selection, deletion or amplification occurring in the embryonic thymus. Another interesting aspect of FT antigens is their reappearance on the surface of thymic leukemia cells. Biochemical studies have indicated that the molecular weight of FT-1 antigen on leukemia cells is about 100,000 by means of biosynthetic labeling with either [3H]-galactose or [35S]-methionine. FT-1 antigen on fetal thymocytes also appeared as a major band with m.w. 100,000. Two-dimensional gel electrophoresis revealed that FT-1 antigenic determinants appear to reside on a family of glycoproteins with extensive charge heterogeneity. All of these results suggest that FT antigens, especially FT-1 antigen, will be useful markers for understanding the mechanism underlying the activation of normally silent genetic information in leukemia cells. In summary, further biochemical and genetic analysis of FT antigens will contribute to an understanding of the ontogenic development of T cells as well as the leukemogenesis of T cell leukemias.

Animals↗
PubMed1986

Interferon-gamma or BCG restores the responsiveness of mouse lung macrophages to lipopolysaccharide.

While mouse peritoneal macrophages respond well to lipopolysaccharide, lung macrophages were neither activated for tumor cell cytotoxicity nor killed directly by it. The unresponsiveness of lung macrophages was ascribed to lack of expression of lipopolysaccharide-binding sites on the cell surface. It was found that in vitro treatment of lung macrophages with interferon-gamma or in vivo sensitization of them with viable BCG restored the response by expression of the lipopolysaccharide binding sites. The modes of action of interferon-gamma and BCG in expressing the binding sites on mouse lung macrophages are discussed.

Animals↗
PubMed1986

[Dural arteriovenous malformation of the anterior fossa with subarachnoid hemorrhage].

Idiopathic dural arteriovenous malformation which occurs in the posterior fossa uses predominantly transverse and sigmoid sinuses. Cavernous sinus comes next and others are rather rare. However, we have recently experienced such a rare case which was operated on and cured completely. The malformation was fed through the anterior ethmoid artery and drained to the cortical vein. The case was a 36-year-old male and admitted in our clinic for having headache and nausea as the chief complaints. He was diagnosed subarachnoid hemorrhage due to the following findings: CT scans showed a high density zone localized in the sylvian vallecula. Cerebrospinal fluid obtained by a lumbar puncture was found to be bloody. No neurological abnormality other than neck stiffness and positive Kernig's sign was observed. Under study of right carotid arteriography, dural AVM was evident. The anterior ethmoidal artery which branched out from the ophthalmic artery fed the AVM. The cortical vein which ran on the surface of the frontal base was its drainer via a small nidus. There was no abnormality seen on a left carotid arteriogram. Surgery was proceeded with the right frontal craniectomy in extra- and intradural approach. At first, anterior ethmoidal artery was cut at the cribriform plate extradurally. After dura was incised, both the nidus and drainer were coagulated intradurally. The nidus was located at inner surface of the dura. The arachnoid hemorrhage was thought to be caused by rupture of this drainer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Synthesis and expression of a human growth hormone (somatotropin) gene mutated to change cysteine-165 to alanine.

We have mutated a synthetic human growth hormone (hGH) gene specifically at the codon for Cys-165 to a codon for Ala by replacement of synthetic deoxyoligonucleotides corresponding to this site. This modification prevented the formation of a disulfide bond between Cys-53 and Cys-165 in the hGH molecule. This mutated protein, [Ala165]hGH was expressed at the same level as the intact hGH, 4 X 10(5) molecules per cell under the control of the tryptophan promoter in Escherichia coli, and retained similar immunological activity to intact hGH. The limited digestion pattern of the mutated protein with human plasmin suggests that the tertiary structure of [Ala165]hGH resembles to that of the intact hGH molecule. [Ala165]hGH revealed full biological activity as examined by the body weight increase of hypophysectomized rats.

Alanine↗
PubMed1985

Lack of binding of bacterial lipopolysaccharide to mouse lung macrophages and restoration of binding by gamma interferon.

Although peritoneal resident macrophages (PRM) or peritoneal exudate macrophages (PEM) were activated by lipopolysaccharide (LPS) to kill tumor cells in vitro, lung macrophages (LM) obtained by mincing lung tissues or by harvesting bronchial lavage were not activated by LPS under any experimental conditions, i.e., different LPS concentrations, incubation times and cytotoxicity assay methods. The unresponsiveness of LM to LPS was seen in all of the mouse strains tested. Treatment of LM with indomethacin did not affect the unresponsiveness, although it greatly augmented the cytotoxicity of PRM stimulated with LPS. LM treated in vitro with crude lymphokines (LK) did not show cytotoxicity, but became sensitive to LPS and cytotoxic for tumor cells. LM treated first with crude LK and then with LPS were cytotoxic, but LM treated first with LPS and then with crude LK were not. The ability of crude LK to render LM responsive to LPS was neutralized by rabbit anti-mouse gamma interferon (IFN-gamma) antiserum but not by anti-mouse IFN-(alpha + beta) antiserum. LM treated with recombinant murine IFN-gamma became responsive to LPS and showed cytotoxicity. LM were resistant to direct toxicity of LPS under conditions in which significant populations of PRM and PEM died. However, LM became sensitive to direct toxicity of LPS by treatment with crude LK or recombinant murine IFN-gamma. Fluorescence microscopy showed that almost all PRM and PEM were stained with fluorescein isothiocyanate (FITC)-LPS, while less than 5% of the LM were stained. Instead, approximately 60% of the LM treated with the crude LK or recombinant IFN-gamma for 20 h were stained with FITC-LPS. Fluorescence-activated cell sorter (FACS) analysis confirmed this result. The staining of IFN-gamma treated LM with FITC-LPS was inhibited by polymyxin B or unlabeled LPS. These results suggest that the defective responsiveness of LM to LPS is due to the lack or very low expression of LPS-binding sites on the cell surface and that in vitro treatment with IFN-gamma brings about the expression of them and renders LM responsive to LPS.

Animals↗
PubMed1985

Production of monozygotic twins following the transfer of bisected embryos in the goats.

Embryos at the morula, blastocyst and hatched blastocyst stage were obtained from superovulated and naturally ovulated Japanese native goats. They were bisected into halves with a glass needle, and transferred immediately or after culture (for morula) to recipients. None of five does which received bisected morula became pregnant. Three of nine goats became pregnant after transfer of bisected hatched blastocysts, six of eleven recipients became pregnant. Four of them produced monozygotic twins and the remaining two produced singles. The present study demonstrated that the hatched blastocyst is suitable for bisection in the goat.

Journal Article↗
PubMed1985

FT-2 antigen for distinguishing lymphocyte subpopulations in the developing thymus.

The surface phenotypes of lymphoid cells in the developing embryonic thymus were characterized by using monoclonal antibodies. FT-2 antigen thus defined was predominantly expressed on thymocytes in the earlier embryonic stages in all the inbred mouse strains tested. The immunofluorescence and immunoperoxidase tests indicated that, like FT-1 antigen, the proportion of FT-2+ fetal thymocytes rapidly decreased with increase in gestation time, and these cells disappeared by day 19 of gestation. The treatment of fetal thymocytes with anti-FT-1 plus complement eliminated not only FT-1+, but also FT-2+ cells, whereas the treatment with anti-FT-2 failed to eliminate approximately 40% of FT-1+ cells, suggesting that embryonic thymocytes can be provisionally divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-.

Animals↗
PubMed1985

Expression of a synthetic human growth hormone gene in yeast.

A synthetic human growth hormone (hGH) gene was efficiently expressed under the control of the repressible acid phosphatase promoter in yeast (Saccharomyces cerevisiae). More than 10(6) molecules of hormone were formed per cell despite the fact that the gene was constructed with codon preference for Escherichia coli.

Alkaline Phosphatase↗
PubMed1985

Macrophage activation by monosaccharide precursors of Escherichia coli lipid A.

Certain Escherichia coli mutants defective in phosphatidylglycerol biosynthesis accumulate two novel glycolipids, designated X and Y. Lipid X is a diacylglucosamine 1-phosphate bearing beta-hydroxymyristoyl groups at positions 2 and 3, and lipid Y has the same structure as X, except for the additional presence of a palmitoyl moiety on the N-linked beta-hydroxymyristate. We have examined the activities of X, Y, and several related compounds as activators of macrophages. Both X and Y induce morphological changes (spreading), prostaglandin E2 synthesis, and killing of tumor cells by mouse peritoneal macrophages in vitro, properties with which lipopolysaccharide and lipid A are also endowed. Both glycolipids have similar effects on the macrophage-like mouse cell line J774.1. Selective removal from lipid X of either the ester-linked beta-hydroxymyristate at position 3 or the phosphate at position 1 abolishes activity. Our results show that the monosaccharides X and Y retain some of the properties of intact lipopolysaccharide and lipid A with respect to macrophage activation. Because the structures of X and Y are defined, our findings should facilitate the elucidation of the molecular mechanism of macrophage activation by lipid A.

Animals↗
PubMed1985

Accessory cell function of a lined macrophage in the induction of suppressor T cells in vitro.

Antigen-specific Ts against DTH to BCG were induced in vitro by culturing the splenic T cells of C3H/He mice together with the lined macrophage, SL-1, pulsed with PPD. The suppressor activity was determined by the suppression of DTH in CY-treated syngeneic recipients which had received the cultured cells before BCG sensitization. SL-1 cells express I-A and I-J antigens on the surface, while SL-4 cells, which originated in the same mouse strain as SL-1, do not express any Ia antigens. When I-A antigens on SL-1 were blocked by anti-I-A antibody without complement before PPD-pulsing, the induction of Ts was rather enhanced. When I-J antigens on SL-1 were blocked by anti-I-J alloantiserum, no Ts were induced. Instead, these I-J-blocked and PPD-pulsed SL-1 cells induced effector cells of DTH in vitro. Ia-negative lined macrophage SL-4 cells did not show any activity either in suppressor or in effector cell induction. From these results, we propose a model for the immune modulation led by APC.

Animals↗
PubMed1985

Effects of gonadotrophins on progesterone production by isolated granulosa cells of the adenohypophysectomized domestic fowl (Gallus domesticus).

Ovine LH and ovine FSH stimulated progesterone production in granulosa cells isolated from the F1, F2 and F3 follicles of hypophysectomized and control (sham-operation) hens when they were collected 6 h after operation, but the steroidogenic response to LH was greater for granulosa cells from hypophysectomized hens. At 15 h after operation progesterone production by granulosa cells was stimulated by LH in all 3 follicle types of control hens, but only in the F1 follicles of hypophysectomized hens. The response to FSH at 15 h was similar for control and hypophysectomized hens. The time after hypophysectomy therefore appears to affect the LH-stimulated progesterone production by granulosa cells of the F2 and F3 follicles.

Animals↗
PubMed1985

[Exfoliative cytology of mixed mesodermal tumors of the uterus--review of cytologic smears sampled prior to therapy].

Nine cases of mixed mesodermal tumor of the uterus were reviewed cytologically. Abnormal cytologic findings were seen in all cases, but malignant cells were detected in only 17 of 30 cytologic smears sampled prior to the therapy (2 of 7 pool smears, 2 of 3 portio rubbing-smears, 6 of 8 endocervical smears and 7 of 12 tumor-rubbing smears). The most commonly encountered cellular components were epithelial malignant cells which showed a close resemblance to those derived from uterine carcinomas, but tended to have multiple nuclei. In other cytologic components, a rhabdomyosarcoma was characterized by large, isolated, round or strap-shaped malignant cells with granular cytoplasms, bizarre and eccentric nuclei and one or more prominent nucleoli. Another infrequent cellular component was a fibrogenic sarcomatous cell which had an illdefined lacy cytoplasm and single or multiple nuclei containing rather finely granular chromatin, and occasionally formed a cluster. In several cytologic specimens, there were also seen multinucleated giant cells which were not in keeping with their histologic origins.

Adenocarcinoma↗
PubMed1985

Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors.

MY-1, a fraction extracted from BCG and composed of 70.0% DNA and 28.0% RNA, was examined for its antitumor activity against 9 different syngeneic mouse tumors. Tumor regression was induced in almost all of the mice bearing any of five kinds of solid tumors by repeated intralesional injections of 100 micrograms MY-1. When cells of some tumors were inoculated intradermally together with MY-1, tumor growth was suppressed, lung metastases were inhibited, and the survival times of mice bearing 1 of 3 leukemic tumors were prolonged. Repeated sc injections with MY-1 in sites remote from tumor cell inoculation or repeated iv injections were more or less effective against three kinds of solid tumors. Mice inoculated with Lewis lung carcinoma cells in a hind footpad and whose legs were amputated 9 days later were given iv or sc injections of MY-1 every other day (8 times in total), resulting in substantial prolongation of survival. No direct cytotoxicity of MY-1 for these tumors could be shown in three kinds of experiments, which indicates that the antitumor mechanism of MY-1 is host mediated. MY-1 was equally effective in mice with or without presensitization with BCG, whereas BCG was much more effective in BCG-sensitized mice. This finding suggests that a delayed-type hypersensitivity reaction elicited by BCG protein is not required for the antitumor activity of MY-1.

Animals↗