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T Hamaoka

Publications and source records attributed to T Hamaoka.

At least 307 records · Page 17Linked to original sources
PubMed1984

Interleukin-1 restores the impaired cytotoxic T lymphocyte generation in beige mutant mouse.

Spleen cells from C57BL/6 beige mouse showed significantly lower cytotoxic T lymphocyte (CTL) generation in vitro against allogeneic target cells as compared with spleen cells from the wild type, whereas the heterozygous littermate showed a response similar to that of the wild type. In contrast, the responsiveness of beige spleen cells in the mixed lymphocyte reaction against allogeneic stimulator cells was in the normal range, suggesting that beige spleen cells recognize allogeneic stimulator cells to the same extent as spleen cells from normal mouse, resulting in a significant proliferation. The addition of interleukin 1 (IL-1)-containing supernatant from lipopolysaccharide-stimulated J774.1 cells to the culture of spleen cells from beige mouse stimulated with allogeneic cells restored the impaired CTL generation in a dose-dependent manner. The molecules responsible for restoration of the impaired CTL response co-migrated with IL-1 on gel filtration. The addition of purified interleukin 2(IL-2) also augmented the induction of CTL from beige spleen cells. However, the magnitude of augmentation by IL-2 was appreciably lower than that of augmentation by IL-1. These results suggest that the role of IL-1 in the induction of CTL is not only to provide a signal for activated amplifier T cells to release IL-2, but also to magnify otherwise low responsiveness of CTL-precursors and/or CTL-helpers. Moreover, intraperitoneal injection of IL-1 without allo-antigenic stimulation was able to restore the in vitro CTL responsitivity to allo-antigen but not the natural killer cell activity, indicating that IL-1 has a therapeutic potential in vivo for preferentially correcting impaired CTL generation associated with beige mutation.

Animals↗
PubMed1984

Distribution, origin, and fine structures of cholecystokinin-8-like immunoreactive terminals in the nucleus ventromedialis hypothalami of the rat.

The distribution, origin, and fine structures of cholecystokinin-8-like immunoreactive ( CCKI ) fibers in the nucleus ventromedialis hypothalami (vm) of the rat were examined using immunohistochemistry. CCKI fibers were moderately concentrated in the ventrolateral part of the vm, decreasing in number dorsomedially. However, no CCKI cells were seen in the vm even in colchicine-treated rats. In addition, the destruction of the lateral part of the nucleus parabrachialis dorsalis (pbd) where numerous CCKI cells were seen resulted in a marked decrease in CCKI fibers in the vm on the operated side. Electron microscopic observations revealed that CCKI terminals make synaptic contact with soma, spine, and the proximal segment of the dendrite. The neurons making synaptic contact with the CCKI fibers had moderately electron-lucent cytoplasm. These findings suggest that the CCKI fibers in the vm originate from CCKI cells in the lateral part of the pbd and directly influence the vm neurons.

Animals↗
PubMed1984

Effector cell analysis of tumor cell rejection in vivo in two syngeneic tumor systems exhibiting distinct in vitro cytotoxic mechanisms.

The nature of the in vivo anti-tumor effector cells was investigated in two different tumor system, MH134 hepatoma and X5563 plasmacytoma, in which tumor-specific antibodies and cytotoxic T lymphocytes (CTL), respectively, mediate in vitro tumor cell lyses. Winn assays utilizing MH134- and X5563-immune spleen cells revealed that in both tumor systems, tumor neutralization was produced exclusively by a tumor-specific immune Lyt-1 T cell subpopulation which was depleted of antibody-producing B cells or T cell subset(s) capable of generating CTL responses. These Lyt-1 T cells could exert their in vivo tumor-protective function under conditions in which MH134 tumor-specific antibody was not detected or in T cell-depleted recipient mice (B cell mice) in which CTL precursors were not recruited, indicating that their activities do not depend on the induction of antibody or CTL response. These results are discussed in the context of the relationships (1) between effector systems detected in in vitro cytotoxicity tests and effector mechanisms responsible for in vivo tumor protection, and (2) between epitopes or molecules required for triggering in vitro and in vivo effectors against the tumor.

Animals↗
PubMed1984

Additional evidence for the augmented induction of tumor-specific resistance in vaccinia virus-primed mice by immunization with vaccinia virus-modulated syngeneic tumor cells.

The augmenting effect of vaccinia virus infection of tumor cells on induction of tumor-specific resistance was examined in mice. C3H/HeN mice were primed intraperitoneally (ip) with live vaccinia virus after whole-body irradiation with 250 rad of X-rays. Three weeks later the mice were immunized ip 3 times at weekly intervals with syngeneic murine hepatoma MH134 or spontaneous myeloma X5563 which had been infected in vitro with vaccinia virus and subsequently irradiated with 7000 rad of X-rays. One week after the third immunization, the mice were challenged with 1 X 10(5) viable cells of MH134 or X5563 ip or 1 X 10(6) tumor cells intradermally (id). On ip challenge with viable MH134 cells all mice that had not been pretreated died within 3 weeks due to ascites tumor out-growth, whereas all mice that had been vaccinia virus-primed and immunized with vaccinia virus-infected MH134 cells survived. On ip challenge with X5563 cells, the percentage survival of vaccinia virus-primed and vaccinia virus-modified tumor-immunized mice was 80%. On id challenge with MH134 and X5563 tumor cells, in un-treated mice tumors grew to more than 5 mm in diameter within 3 weeks, whereas 90% and 60%, respectively, of the mice that had been vaccinia virus-primed and immunized with vaccinia virus-infected tumor cells showed no tumor out-growth. Pretreatment by only immunization with vaccinia virus-infected cells or vaccinia virus-priming and immunization with virus non-infected tumor cells were not effective for preventing induction of tumor-resistance to either ip or id challenge with MH134 or X5563 tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Selective elimination of a B cell subset having acceptor site(s) for T cell-replacing factor (TRF) with biotinylated antibody to the acceptor site(s) and avidin-ricin A-chain conjugate.

A covalent conjugate of avidin with ricin subunit A-chain (avidin-RA) was prepared by using N-succinimidyl 3-(2-pyridyldithio)propionate as a coupling agent. Selective cytotoxic activity after the combined treatment of spleen cells with biotinylated antibody and avidin-RA was demonstrated by the fact that the responsiveness to LPS was selectively abrogated by pretreatment of the cells with biotinylated rabbit anti-mouse immunoglobulin (MIg) antibody, but not with biotinylated anti-Thy-1.2 antibody. Neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the responses to mitogens. Moreover, a high anti-DNP PFC response elicited by DNP-KLH-primed BALB/c mouse spleen cells stimulated in vitro with DNP-KLH was mostly abrogated by the pretreatment of the cells with biotinylated anti-MIg antibody and avidin-RA. Again, neither the biotinylated antibody alone nor avidin-RA alone was effective in decreasing the anti-DNP PFC response. This cell-killing method with the use of biotinylated antibody and avidin-RA was applied and evaluated in experimental systems in which the helper action of T cells on B cells was mediated by T cell-replacing factor (TRF) or was performed by the direct interaction of T cells with B cells (cognate interaction). When DNP-KLH-primed splenic B cells, pretreated with biotinylated F(ab')2 fragment of DCF1 male anti-BALB/c-B IgG antibody against acceptor site(s) for TRF followed by treatment with avidin-RA, were stimulated with DNP-OVA in the presence of monoclonal TRF, the anti-DNP PFC response was significantly decreased, whereas the same treated B cells responded well to stimulation with DNP-PPD in the presence of Tbc-primed T cells (cognate interaction). These results indicate that B cells responsible for the cognate interaction and those having TRF acceptor site(s) belong to a distinct subpopulation of B cells, and that the cytocidal action of the noncovalent conjugate of the antibody and RA formed from the biotinylated antibody and avidin-RA via an avidin-biotin complex has immunologic selectivity, eliminating only the latter subset of B cells recognized by the antibody.

Animals↗
PubMed1983

Ontogeny of cholecystokinin-8-containing neuron system of the rat: an immunohistochemical analysis. I. Forebrain and upper brainstem.

Ontogeny of the cholecystokinin-8 (CCK) neuron system in the forebrain and upper brainstem of the rat was investigated by means of indirect immunofluorescence. CCK cells and fibers first appeared in the developing ventral tegmental area and in the primordium of the medial forebrain bundle, respectively, at gestational day 15 (12-14-mm embryos). From that time, CCK cells appeared in various areas of the forebrain and upper brainstem until birth and reached the maximum content at postnatal day 10. After postnatal day 10, although CCK cells tended to decrease slightly in number, colchicine treatment in the adult rats brought out numerous CCK cells in the same areas. In contrast, although CCK fibers developed only slightly during the fetal period, marked development was seen after birth, particularly between postnatal days 5 and 10. After that time, as the rats grew, CCK fibers continued to increase in number and formed a meshwork of varying density in various areas of the forebrain and upper brainstem.

Animals↗
PubMed1983

Ontogeny of cholecystokinin-8 containing neuron system of the rat: an immunohistochemical analysis--II. Lower brain stem.

The ontogeny of the cholecystokinin-8 neuron system in the lower brain stem of the rat was investigated by means of indirect immunofluorescence. Cholecystokinin-8-like immunoreactive structures first appeared in the primordium of the ventral tegmental area, ventral tegmental nucleus of Gudden and the area lateral to the superior central nucleus of the fetus on gestational day 17. Although cholecystokinin-8-like immunoreactive structures appeared gradually in various lower brain stem areas from this day, and developed markedly from postnatal day 6, thereafter, the ontogeny of cells and fibers was different. In general, the fibers increased in number as the rats grew and reached the maximum in adulthood, whereas the cells reached a maximum number between postnatal days 6-12, after which they decreased in number. Colchicine treatment, however, demonstrated the presence of cholecystokinin-8-like immunoreactive cells in various areas of the lower brain stem. These findings suggest that the cholecystokinin-containing neuron system is active in the adult and that cholecystokinin-containing cell somata cannot store a sufficient amount of the peptide for visualization in the absence of colchicine. Thus, it might be concluded that cholecystokinin may play an important role in the brain function of the adult as a neurotransmitter or neuromodulator, though its exact function is now open to discussion.

Animals↗
PubMed1983

The distribution of cholecystokinin octapeptide-like structures in the lower brain stem of the rat: an immunohistochemical analysis.

The distribution of immunoreactive cholecystokininoctapeptide (CCK-8)-like structures in the lower brain stem of the rat was investigated using indirect immunofluorescence. In addition to the well known immunoreactive CCK-8-like containing cell groups such as those in the ventral tegmental area, substantia grisea centralis of the mesencephalon, and n. linealis rostralis, the present study demonstrated a much wider distribution of immunoreactive CCK-8-like cells in the lower brain stem, i.e. those in the inferior colliculus, n. parabrachialis colliculi posterioris, lateral lemniscus, lateral parabrachial area, n. centralis superior, nucleus of group O, pontine substantia grisea centralis, n. tractus solitarii, area postrema, n. tractus spinalis nervi trigemini and reticular formation just dorsal to the inferior olivary complex. We also demonstrated an extensive network of immunoreactive CCK-8-like fibers in various areas of the lower brain stem, including the auditory system, visual system, viscerosensory area, parabrachial nucleus, dorsal and ventral tegmental nuclei, and interpeduncular nucleus. The possible importance of CCK is briefly discussed.

Animals↗
PubMed1983

Soluble factors involved in B cell differentiation: identification of two distinct T cell-replacing factors (TRF).

Highly purified B lymphocytes cultured with affinity-purified goat anti-mouse IgM antibodies and B cell growth factor (BCGF) proliferate but fail to differentiate into immunoglobulin-synthesizing cells during 4-day cultures. Induction of immunoglobulin (Ig) synthesis depends on the presence of two additional T cell-derived factors (T cell-replacing factors [TRF]). One TRF, designated B15 1K 12-TRF, is found in the supernatant of B15 1K 12 T hybridoma cells. It is required relatively early in these cultures and appears to cause an increase in cell yield as well as Ig synthesis. The second factor, designated EL-TRF, is found in PMA-induced EL-4 supernatant. It appears to be different from both BCGF and IL 2 in that it can be separated from the former by isoelectric focusing and from the latter by phenyl-Sepharose chromatography. EL-TRF is still active if added on the last day of a 4-day culture. A model for the action of anti-IgM and these three T cell-derived factors in B cell activation and differentiation is proposed.

Animals↗
PubMed1983

Plasma cholecystokinin responses after ingestion of liquid meal and intraduodenal infusion of fat, amino acids, or hydrochloric acid in man: analysis with region specific radioimmunoassay.

A highly sensitive and precise radioimmunoassay system for plasma cholecystokinin (CCK) was developed with the anti-CCK-8 specific antiserum which raised against N-terminal amino acids residue of sulfated CCK-8 and reacted with CCK-8, CCK-33, and CCK-39 but not with gastrin and its related peptides. Mean concentration of the fasting plasma CCK determined with this method using CCK-8 as standard was 12.9 +/- 5.9 pg/ml in normal subjects (n = 26), and in patients with hepatic cirrhosis it was significantly higher (36.7 +/- 16.9 pg/ml, n = 9, p less than 0.01) than in normal subjects. In six young healthy volunteers, intraduodenal infusion of fat caused a significant increase (p less than 0.05) of plasma CCK from a basal level of 8.0 pg/ml to a peak of 43.0 +/- 12.0 pg/ml at 20 min after starting of infusion. In the same subjects, a significant increase of plasma CCK was also observed by amino acids infusion, but no elevation of plasma CCK level was found during intraduodenal acidification.

Adult↗
PubMed1982

Production of rabbit antibody specific for amino-terminal residues of cholecystokinin octapeptide (CCK-8) by selective suppression of cross-reactive antibody response.

Antibody specific for the amino-terminal region of cholecystokinin octapeptide (CCK-8) was generated in a highly reproducible way in New Zealand white rabbits by a novel immunization procedure which involves immunization with CCK-8 peptide conjugate coupled with keyhole limpet hemocyanin (KLH) and inhibiting cross-reacting antibody formation by treatment of the animals with a potent tolerogenic conjugate of beta-alanyl-tetragastrin and a copolymer of D-glutamic acid and D-lysine (D-GL). The antisera thus produced specifically react with an amino-terminal region of CCK-8 but not with the non-sulfate form of CCK-8, nor with the carboxy-terminal region which shares a cross-reactive determinant among gastrin and cholecystokinin-related peptides (caerulein, CCK-4, CCK-8, CCK-33 and CCK-39). The antisera produced by this method allowed us to measure specifically CCK in extracts from tissue such as duodenum containing gastrin and CCK at comparable levels.

Amino Acids↗
PubMed1982

Identification of a T cell-derived b cell growth factor distinct from interleukin 2.

We report here a factor (B cell growth factor) found in induced supernatants of the mouse thymoma EL4 that co-stimulates with anti-IgM antibodies in short-term cultures of purified B lymphocytes to induce polyclonal B cell proliferation but not antibody-forming cell production. The factor is not mitogenic for resting B cells and interacts with anti-IgM-activated B cells in a non-H-2-restricted manner. Absorption studies and molecular weight analysis reveal the factor is distinct from interleukin 2. This factor synergises with antigen, interleukin 2, and an interleukin 2-free, B cell growth factor-free T cell supernatant that contains T cell-replacing factor to produce erythrocyte-specific plaque-forming cells in cultures of highly purified B cells.

Animals↗
PubMed1982

Detection and characterization of idiotype-specific enhancing cells generated in mice immunized with idiotype.

Cellular interaction between MOPC-104E (M104E) cross-reactive idiotypic (CRI) antibody-producing B lymphocytes and lymphocytes generated by immunization with the relevant idiotype, M104E, was investigated. Adoptive transfer of M104E idiotype-primed and normal spleen cells into 600R x-irradiated syngeneic recipient mice resulted in striking enhancement of the M104E-CRI positive antibody response upon simultaneous immunization of recipients with dextran B1355S. The enhancement was not attributable to a simple additive effect but was due to synergistic cooperation between the two lymphocyte populations. This synergistic enhancement of the anti-idiotype immune cells producing CRI antibody was specific for MOPC-104E CRI, and was reproducible in an in vitro culture system. Because of the cellular characteristics of the enhancing cells, they were assumed to be B lymphocytes specific for the corresponding idiotype, since the activity was not abrogated by treatment with anti-Thy-1, anti-Lyt-1, anti-Lyt-2, or anti-brain-associated theta antisera plus complement, but was eliminated by means of a planning method using a rabbit-anti-mouse immunoglobulin-coated or idiotype-coated dish. The mechanisms of interaction between the CRI-positive B cells and anti-idiotypic B cells in response to the thymus-independent antigen dextran B1355S are discussed.

Animals↗
PubMed1982

Effect of helper T cells on prevention of tolerance induction in effector T cells responsible for syngeneic tumor immunity.

The present study investigates the role of helper T cells in preventing tolerance in effector T cells responsible for syngeneic tumor immunity. Tolerance in T cell-mediated immune responses against X5563 plasmacytoma was induced in syngeneic C3H/He mice by intravenous (iv) administration of 7,000 R X-irradiated X5563 tumor cells. Since the anti-X5563 tumor tolerance was observed irrespective of whether the tumor cells had been modified with trinitrophenyl (TNP) hapten prior to iv inoculation, the ability of TNP-reactive helper T cells to prevent the tolerance induced by iv inoculation of TNP-X5563 tumor cells was examined. TNP-reactive helper T cell activity was generated in C3H/He mice by immunization with TNP-isologous mouse gamma-globulin after inoculation with the TNP-conjugate of a non-immunogenic co-polymer of D-glutamic acid and D-lysine. Intravenous inoculation with TNP-modified X5563 cells induced tolerance in mice not primed with TNP. However, such tolerance was prevented in mice in which TNP-reactive helper T cell activity had been generated. These results indicate that helper T cells play a crucial role in preventing effector T cell tolerance. The mechanisms by which tolerance induction in effector T cells is circumvented are discussed in relation to the generation and delivery of signals required for T cell activation.

Animals↗