Suppressor T cells belong to the self-reactive repertoire.
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Animals↗
Biomedical subjects
M Taniguchi
Publications and source records attributed to M Taniguchi.
Specific inhibition of class II MHC gene expression by anti-sense RNA.
We have established an anti-sense RNA system which is capable of regulating expression of the class II (Ia) molecule coded for by the major histocompatibility complex in cultured mouse cells. Various areas of the I-A beta chain gene were subcloned in an anti-sense orientation to the 3' of the dihydrofolate reductase (DHFR) cDNA under the control of the human metallothionein IIa gene promoter. These anti-sense DNA constructs were transfected into M12.4 cells, a BALB/c B lymphoma cell line which expresses both I-A and I-E molecules on the cell surface. I-A expression of selected clones transfected with anti-sense DNA encompassing the 5' untranslated region (UT) (100 or 310 bp) including the translation start site or the poly(A) addition signalling sequence in the 3' UT (250 bp) of the I-A beta chain gene were specifically reduced to less than 5% of the control M12.4 cell surface I-A expression. These clones had normal levels of I-E expression. However, transfection of the anti-sense DNA to the beta 1 domain (510 bp) including the splicing donor and acceptor sequences did not affect the expression of I-A molecules. The same antisense DNA constructs (100 bp of the 5' UT or 250 bp of the 3' UT) without the DHFR cDNA (710 bp) did not down-regulate the expression of I-A molecules, indicating that either the physical length of the anti-sense RNA or specific DHFR cDNA sequences are also important.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Predominant use of a particular alpha-chain in suppressor T cell hybridomas specific for keyhole limpet hemocyanin.
We isolated and sequenced the rearranged genomic variable (V) and joining (J) gene segments of T cell receptor alpha-chain gene from two independent keyhole limpet hemocyanin (KLH)-specific suppressor T cell (Ts) hybridomas (BW5147 x C57BL/6 KLH-Ts). These nucleotide sequences were compared with those of germline DNA from kidney and also with cDNA of alpha-chain (VJ alpha 281) previously isolated from Ts hybridoma (34S-281) with KLH/H-2b Ts activity. The entire V alpha and J alpha sequences of all three Ts hybridomas were exactly identical and were encoded by the germline V alpha and J alpha gene segments without any mutations, except for 2-nucleotide deletions from both the 3' end of V alpha and 5' end of J alpha gene segments, respectively, and a 1-nucleotide (guanine) insertion in the junctional (N) region which was not encoded by the germline gene. Six additional KLH-Ts hybridomas, further analyzed, also possessed the same alpha-chain, indicating the preferential usage of the particular alpha-chain in these hybridomas. As chromosome analysis demonstrated a different pattern in each clone, these hybridomas appear to be independent. More surprisingly, 0.5-1.5% of the total functional T cell alpha-chain mRNA in the thymus and spleen of unprimed C57BL/6 mice was found to be of this particular alpha-chain. These results suggest that the repertoire of KLH-Ts is strictly limited.
Amino Acid Sequence↗
Genomic DNA with transformation-related activity and melanoma antigen expression.
We have analyzed the mouse melanoma antigen with monoclonal antibodies established by syngeneic immunization. To further understand the structure of this antigen at a molecular level, we have cloned the genomic DNA controlling the expression of melanoma antigen by cosmid library transfection and a monoclonal antibody. In the process of analyzing this DNA fragment we found that it contained a gene related with transformation, which was proved by tumor formation in nude mice inoculated with NIH/3T3 transfectants of this DNA fragment. We discuss the structure of the gene product based on the deduced amino acid sequence of cDNA, which maps the genome bearing transformation-related activity.
Animals↗
Properties of mouse melanoma antigen and its secretion mechanism from the cell surface.
We analyzed the biochemical properties and biological significance of the melanoma antigen secreted in the culture supernatants of B16 melanoma cells. The 80 kilodalton (kd) molecule bearing the epitopes of mouse melanoma antigen was found to associate noncovalently with an 18 kd moiety in the culture supernatants as well as on the cell surface. Tunicamycin treatment of B16 cells did not affect the expression of the 69 kd nonglycosylated form of the 80 kd molecule but did abolish the association between the two molecules on the cell surface. We could not detect this antigen as a soluble form when the N-linked glycosylation was inhibited. Therefore, the glycosylation of the 80 kd molecule is essential for the formation of the 80 kd/18 kd complex and also for the secretion. Moreover, the affinity-purified melanoma antigen from the supernatants could induce anti-melanoma suppressor cells which block the generation of cytotoxic T lymphocytes against melanoma cells. Thus, the 80 kd glycoprotein as a soluble melanoma antigen performed a pivotal function in the escape mechanisms of melanoma cells from the host immune surveillance system.
Animals↗
Density of GM3 with normal primary structure determines mouse melanoma antigenicity; a new concept of tumor antigen.
We attempted to induce anti-melanoma cytotoxic T cells (CTL) and suppressor T cells (Ts) inhibiting CTL generation by using liposomes carrying various densities of GM3 as tumor antigens. We found that liposomes carrying 6-16 mol% of GM3 with normal primary structure successfully generated anti-melanoma CTL and suppressor T cells, while liposomes with GM3 outside this range had little or no such activity. Anti-melanoma CTL induced by GM3(NeuGc)-liposomes belonged to CD4-/CD8- double-negative CD3+ CTL while GM3(NeuAc)-liposomes induced two types of T cells, CD4+ T cells and double-negative I-J positive T cells which mediated inhibition of the induction of anti-melanoma CTL responses. These cell types were the same as those induced by mitomycin C-treated melanoma cells for CTL induction and soluble melanoma antigen for Ts generation. The results clearly demonstrate that even GM3 with normal primary structure can, at a certain density, generate melanoma antigenicity.
Animals↗
Two cases of cystic fibrosis in Japanese children: studies on the essential fatty acid and prostaglandin metabolism.
We describe the fatty acid (FA) and prostaglandin (PG) metabolism in two Japanese cases of cystic fibrosis (CF) with or without pancreatic insufficiency (PI). The diagnosis of CF was based on the elevated sweat chloride concentration by pilocarpine iontophoresis. A 1-month-old boy (case 1) showed poor weight gain, steatorrhea and scaly dermatitis, but no respiratory symptoms were noted. He had decreased levels of serum linoleate and arachidonate, and increased palmitoleate and oleate levels, indicating essential fatty acid (EFA) deficiency. Supplementation of fat-emulsion improved his skin lesions and the altered FA pattern within a few months, associated with the definite reduction of the urinary PG F2 alpha levels. Until two years of age, he has been free from respiratory symptoms. A 12-year-old girl (case 2) had had recurrent respiratory tract infections due to Pseudomonas aeruginosa and Staphylococcus aureus for several years, and her pancreatic functions were preserved. The FA patterns of her serum lipid were almost within the normal range. These results indicate that 1) the altered FA composition appeared to be a secondary consequence of PI commonly complicating CF and 2) the correction of the altered FA and PG metabolism might have a beneficial effect on the respiratory function of CF patients with EFA deficiency.
Child↗
Small, superficial esophageal carcinoma treated with high-dose-rate intracavitary irradiation only.
Six patients with small, superficial carcinoma of the esophagus were treated with 18-24 Gy of high-dose-rate intracavitary irradiation only. All patients were examined with an endoscope within 1 month after therapy, and the tumor in all six had disappeared. However, erosion induced by high-dose-rate intracavitary irradiation was seen in five of the patients. Five of the patients have experienced no local recurrence; endoscopic biopsy showed local recurrence in the remaining patient 7 months after radiation therapy. All patients have survived 6-16 months. Esophageal ulceration induced by intracavitary irradiation occurred in three of the six patients; however, the ulcers have been healing with conservative treatment. This new method of using only high-dose-rate intracavitary irradiation appears to be effective in the patient with small, superficial esophageal carcinoma.
Aged↗
Biochemical characterization of an antigen-specific suppressor T cell factor.
We describe here the biochemical properties of suppressor T cell factor (TsF2) released from an inducible anti-idiotypic T cell hybridoma (C57BL/6 T cell x BW5147) which mediates antigen (keyhole limpet hemocyanin) specific and genetically (H-2b) restricted suppression of IgG plaque-forming cell responses. We examined the suppressive activity by in vitro functional assay in fractions of chromatography and in the materials eluted from gels of sodium dodecyl sulfate polyacrylamide and isoelectric focusing and determined the molecular weight(s) (22-37 kD) and the isoelectric point(s) (pH 6.0-6.1) of this secreted factor. Messenger RNA products of the hybridoma translated in the rabbit reticulocyte lysate system were similarly examined, and the functionally active molecule was seen to migrate to almost the similar molecular weight(s) (23-40 kD), and isoelectric point(s) (pH 5.5-6.2) range as those of secreted TsF. Moreover, the TsF activity was recovered from gel slice corresponding to the similar molecular weight range analyzed in sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing and nonreducing conditions. Thus, we speculate that this molecule is composed of a single chain, biologically active. Comparison of autoradiograms on in vitro translation products between activated and resting hybridomas by two-dimensional gel electrophoresis showed that the molecular weights and isoelectric points of two spots (28 kD, 5.7; 25 kD, 5.5) newly appearing or markedly enhanced after activation in the area with suppressor activity were concordant with the data on secreted TsF, suggesting that one of these two spots represents the functional molecule which causes antigen-specific and genetically restricted suppression of IgG responses.
Animals↗
[Studies on the constituents of Leucoseptrum stellipillum].
Flavonoids, triterpenoids, and steroids were isolated from the leaves of Leucoseptrum stellipillum (MIQ). Kitamura et Murata and identified as apigenin, luteolin, chrysoeriol, ursolic acid, pomolic acid, tormentic acid, beta-sitosterol, and beta-sitosterol glucoside by comparison of their spectral data with those of authentic specimens. Among these compounds, the triterpenoids showed significant antibacterial activities against Streptococcus mutans.
Bacteria↗
Japanese consonants compared with English with regard to prosthodontic dentistry.
This is the introductory paper of the forthcoming series of papers on Japanese consonants compared with English, presented as a basic study for prosthodontic dentistry. Materials for our experiment are fifteen groups of Japanese and English words and phrases to be uttered by normal native speakers of Japanese and English respectively. They are speakers of a modified standard Japanese and the Hichiku (: part of northern Kyushu) accent of Japanese and those of standard British English, General American English and Eastern American English. Each of the fifteen groups of words and phrases contains a set of Japanese and English consonants to be examined and compared with each other. The phonetic apparatus to be used are the sound spectrograph, oscillograph, phono-laryngograph, flow-nasalitygraph, electro-palatograph, etc.
Dentures↗
[GM3 ganglioside as melanoma specific antigen and its biological function].
We have shown that a syngenic monoclonal antibody, M2590, established after immunization of C57BL/6 mice with B16 melanoma cells, recognized GM3 (NeuAc) ganglioside. Although GM3 is widely distributed among various normal cells and tissues, the antibody did not react with them. However, it reacted exclusively with melanoma cells from mouse, hamster and human. Preliminary experiments suggested that proteins and lipids as well as GM3 density on B16 cells are involved in the reactivity of GM3 with the antibody. Then, we investigated the biological function of the melanoma antigen, which was secreted from B16 cells into the culture medium. This soluble antigen was shown to suppress the positive immune responses by inhibiting CTL activity in the effector phase and by induction of specific suppressor T cells (Ts) that block CTL generation in the induction phase. Liposomes containing GM3 (NeuAc) but not GM3 (NeuGc) can effectively induce the melanoma specific Ts as did the soluble antigen. The results indicated the tumor cells can escape from host-immune system by stimulating the repertoire of Ts for self-antigen, GM3. To understand the biological role of GM3, we have established mutant clones of no-expressor of GM3 recognized by M2590. The clones were found to have lower attachment to laminin and type IV collagen and poor ability of lung metastasis.
Animals↗
[Evaluation of ischemia by exercise stress Tl-201 myocardial SPECT in silent and symptomatic ischemia].
Forty patients with ischemic heart disease confirmed by coronary arteriography were performed Tl-201 stress myocardial scintigraphy using SPECT. Fifteen patients had anginal attack during exercise Tl-201 myocardial perfusion study (symptomatic group), and 25 patients had horizontal or downsloping ST segment depression more than 0.1 mV without angina (asymptomatic group). The washout maps were derived from circumferential profile analyses of tomographic short-axis slices, and the data were plotted as a bull's eye map. The patient's washout map was compared with the lower limit of normal (mean--2 SD), and the extent and severity scores were calculated. On visual analysis 87% (13/15) of symptomatic patients showed redistribution, while only 56% (14/25) of asymptomatic patients showed redistribution (p less than 0.05). The extent score was significantly higher in the symptomatic group than in asymptomatic group (37.2 + 23.6 vs. 19.6 + 20.8, p less than 0.05), but severity score was slightly higher in symptomatic group (56.1 + 59.4 vs. 30.0 + 54.8, NS). In conclusion, symptomatic ischemia may be more severe than asymptomatic one and the degree of ischemia may be one of the factors that determine the presence of angina during ischemia.
Adult↗
[Evaluation of ischemic heart disease by thallium-201 washout-rate map using SPECT].
In thallium-201 myocardial perfusion scintigraphy, washout rate (WR) has been used for the evaluation of the severity of ischemic heart disease (IHD). The WR was calculated from the polar map (Bull's-eye display) of myocardial perfusion using SPECT. To analyze the abnormality of WR map, we computed the extent and severity scores of WR. Applications of two types of standards, absolute and relative standards from control group (n = 16), were compared. The multiple regression analysis showed that the global WR was a function of the severity of coronary artery stenosis and exercise level, i.e. WR (%) = -2.38 X (number of stenotic artery) + 0.093 X (rate-pressure product/100) + 19.7 (n = 62, r = 0.63). Thus in evaluating the severity of IHD by absolute WR, the correction of WR was necessary according to the exercise level. Whereas, to evaluate the score of WR abnormality in polar map, the relative standard separated each group with different number of stenotic artery better than absolute standard did. In conclusion, calculation of WR score from relative standard is recommended for the analysis of polar WR map, although absolute global WR is useful for the evaluation of severity of coronary artery disease.
Coronary Disease↗
[Separate evaluation of beta-methyl fatty acid uptake and perfusion in rat myocardium].
The kinetics and distribution of I-125 beta-methyl iodophenyl pentadecanoic acid (BMIPP) in rat's heart were studied for separate evaluation of perfusion and metabolism. Tl-201 and BMIPP were simultaneously injected. The experimental groups consisted of control (C), glucose (G) and sodium lactate loaded group (L). In C, myocardial uptake at 5 minutes after BMIPP injection was 3.60% ID/g and remained constant up to 60 minutes. The myocardium/lung ratio (2.44) and the myocardium/muscle ratio (4.55) of BMIPP were almost equal to those of Tl-201. But myocardium/liver ratio was low (1.31). In G, myocardial uptake of BMIPP (1.94 +/- 0.36% ID/g) and g-BMIPP/Tl (0.31 +/- 0.03) at 15 minutes after injection were significantly decreased (p less than 0.001) than those of C (3.16 +/- 0.18% ID/g and 0.48 +/- 0.05). In L. myocardial perfusion was decreased and g-BMIPP/Tl (0.73 +/- 0.14) was significantly higher (p less than 0.01) than those of C. Coefficient of variance of the density within a myocardium, and the ratio of inner to outer layer of myocardium (I/O ratio) were calculated from autoradiogram by videodensitometry. The myocardial distribution of BMIPP was more inhomogeneous, and the I/O ratio was lower than that of Tl-201, although these were not specific for metabolic interventions. In conclusion BMIPP is suitable for SPECT imaging and dual nuclide imaging by BMIPP and Tl-201 will provide informations about myocardial fatty acid metabolism and perfusion.
Animals↗
Histoincompatible skin and marrow grafts in mice given cholera toxin.
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Animals↗
Cholera toxin induced tolerance to murine allografts.
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Animals↗
Characterization of a melanoma antigen with a mouse-specific epitope recognized by a monoclonal antibody with antimetastatic ability.
We have characterized properties of a melanoma antigen with a mouse-specific melanoma epitope expressed on B16 melanoma by using syngeneic monoclonal antibodies with antimetastatic ability. The molecule recognized by the antibody is a membrane glycoprotein with a molecular weight of 80,000. Studies on tunicamycin treatment indicated that the core size of the molecule appeared to have a molecular weight of 69,000 and also suggested that the carbohydrate moiety was greatly responsible for the conformation of the mouse melanoma epitope. The antigen was released or shed into the culture medium from the cell surface, and the turnover rate of the antigen was within 1.5 h.
Animals↗