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T Natori

Publications and source records attributed to T Natori.

At least 91 records · Page 5Linked to original sources

Chemically induced rat B cell leukemia KNL-14, and its major histocompatibility complex products.

Five rat leukemia cell lines induced with chemical agents and/or leukemia viruses were investigated in terms of their surface antigens. One of them, KNL-14, which was induced with 1-butyl-1-nitrosourea in WKA rats had RT1-B region-associated antigens on the cell surface. In addition, Thy-1.1 antigens and surface and cytoplasmic mu chains were detected by serological and immunochemical means. From the results it was concluded that this leukemia originated from immature B cells. In the present work, RT1 antigens on the KNL-14 cells were further investigated. The class I and class II antigens were examined and KNL-14 cells were found to have phenotypical antigens and immunogenicity similar to those of B cells from the WKA lymph nodes. As for class II antigens, which are responsible for various immunologic functions, two specificities were detected, Ba-1.2 and Ba-2.7. These KNL-14 cells should be useful for studying the process of rat B cell differentiation and for immunochemical studies of the rat MHC gene products.

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Natural antibodies carrying a cross-reactive idiotype enhance tumor growth in the rat.

A population of Fab fragments was identified in the papain-solubilized fraction of membranes of a rat chemically-induced sarcoma, KMT 17. The Fab fragments were partially purified by gel filtration and column electrophoresis. A rabbit antiserum against the partially purified Fab fragments was raised and shown to be specific for Fab fragments by immunoelectrophoresis. Furthermore, four lines of evidence indicated that the KMT 17 Fab fragments carry a cross-reactive idiotype: (1) the antiserum could bind only with a restricted population of normal Fab fragments having a pl of 6.3; (2) an unrelated antibody (WKA anti-SRBC) showed a weak cross-reactivity (less than 6%); (3) syngeneic antisera against the KMT 17 could bind with the 125I-KMT 17 Fab preparation that was purified by an immunoabsorbent column with the rabbit anti-KMT 17 Fab antiserum (anti-idiotype antibody); (4) the rabbit anti-KMT 17 Fab antiserum could bind with neither heavy nor light chains of WKA IgG. The natural antibody carrying the idiotype was found in normal serum and in various organs as well, especially in the lung of the conventional rats. In addition, the fractions containing Fab fragments (Frll) were shown to enhance tumor growth when injected into syngeneic animals, whereas Fab-free fractions that were separated from the Fab fragments by column electrophoresis showed no enhancing activity. These results strongly suggested that a population of Fab fragments carrying a cross-reactive idiotype was responsible for the enhancement of tumor growth. Mechanisms for the biological function of natural anti-tumor antibodies carrying a cross-reactive idiotype are discussed.

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The B region-associated antigens and MLR phenotypes in the Japanese inbred strains of rats.

Seven different alloantisera absorbed with red blood cells (RBC) from appropriate strains of rats detected a series of B cell alloantigenic specificities that could be divided into two groups, presumably coded for by at least two different closely-linked loci in the rat major histocompatibility complex (MHC), RT1. The one locus had two allele codes for a broad specificity and the other locus codes for a unique specificity that was found only in the restricted strains of rats that shared the same mixed lymphocyte reaction (MLR) phenotype. RBC-absorbed alloantisera were monitored against a panel of B cell fractions obtained from sixteen inbred strains. Two alloantisera, ACI anti-W and W anti-TO detected two broad specificities, into either of which all inbred strains tested were classified. Two broad RT1-B region-associated specificities were thus designated provisionally as Ba-1.1 and -1.2. Another five alloantisera detected four respective specificities which have a narrower strain distribution. Sixteen inbred strains were classified into one of five specificities detected by W and F344, F344 anti-SDJ, WKA anti-ACI, W anti-BUF and ACI anti-W absorbed with LEJ lymph node cells. Each specificity was designated provisionally as Ba-2.1, -2.2, -2.4, -2.6, -2.7, respectively. A complete association of Ba-2 specificities with MLR phenotype was observed. Antigenic specificities of Ba-2.2, -2.2 and -2.4 were all classified in a group of Ba-1.1 specificity, whereas Ba-2.6 and -2.7 specificities were associated with Ba-1.2 specificity. This relationship suggested a linkage disequilibrium between the two loci for the Ba antigens.

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[Experimental yolk sac tumors in the rat (author's transl)].

A study on the experimentally induced yolk sac tumor in the rat was made in special regard to the characteristics and origin of tumor cells. Pregnant rats which fetuses were removed on the 12th day of gestation, developed tumors derived from the fetal membranes left outside the uterus, which were composed of differentiated teratomas and yolk sac tumors. Serial observation of the oncogenesis revealed that an early lesion of the yolk sac tumor appeared in a nodule found as early as 3 weeks after the fetectomy and production of alpha-phetoprotein (AFP) was observed histochemically in the tumor cells 5 weeks after the fetectomy. A cultured cell line established after cloning from the transplantable yolk sac tumor which had been induced similarly and converted into ascitic form was also investigated. Light and electron microscopic studies on both induced tumors and the cultured cells indicated a similarity of AFP producing tumor cells with parietal yolk sac cells and of PAS-positive hyaline-like substance with the Reichert membrane. It is reasonable to conclude that the yolk sac tumor observed is regarded as a parietal yolk sac carcinoma described by Pierce. Histogenesis of the tumor is also discussed.

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Immunochemical evidence of a tumor-specific surface antigen obtained by detergent solubilization of the membranes of a chemically induced sarcoma, meth-A.

We reported previously the partial purification of detergent-solubilized specific tumor rejection antigen of a chemically induced sarcoma, Meth-A. During the course of the study, rabbit antiserum against a partially purified specific tumor rejection antigen preparation was raised and rendered specific by in vivo absorption. In this report we show that an antigenic molecule defined by in vivo-absorbed rabbit antiserum, which we tentatively refer to as tumor-specific surface antigen, was solublized by detergent Nonidet P40, and extensive attempts at purification were carried out by a sequence of procedures including gel filtration, isotachophoresis, and polyacrylamide gel electrophoresis. The most highly purified tumor-specific surface antigen retained some specific tumor rejection antigen activity, suggesting an association of the two activities. Both antigens were shown to have a molecular weight of about 60,000 and an electrophoretic mobility of alpha-globulin.

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Cellular immunity to solubilized tumor antigens of a methylcholanthrene-induced sarcoma with a migration inhibition assay.

BALB/c mice immunized with Nonidet P-40 (NP-40) crude solubilized (CS) extracts of a syngenetic methylcholanthrene-induced BALB/c sarcoma (Meth A) were challenged with viable Meth A cells to determine the ability of the solubilized preparations to induce transplantation rejection. Animals resisting such challenge were then used in agarose microdroplet macrophage migration inhibition (MMI) and tumor cell neutralization (Winn) assays to evaluate the antigenic specificity of these CS extracts. Spleen cells from those animals that rejected Meth A after immunization with the NP-40-solubilized preparations effectively neutralized the tumor-producing capacity of Meth A tumor cells as determined in Winn assays. MMI assays were quite sensitive and detected migration inhibition of peritoneal exudate (PE) cells from immunized mice with extract concentrations as low as picogram quantities. Specificity studies demonstrated that Meth A expressed no antigenic cross-reactivity with similarly prepared extracts of an unrelated SV40-induced sarcoma (mKSA), nor with a mineral oil-induced plasmacytoma (ADJ-PC5) of BALB/c mice. Inhibition of PE cell migration was mediated by culture supernatants (presumably migration inhibition factor [MIF]) generated from a mixture of immune spleen cells and mitomycin C (MMC)-treated Meth A cells as assayed in an indirect MMI test.

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Cell-mediated immunity against particulate and solubilized tumor-associated antigens of murine plasmacytomas detected by macrophage migration inhibition assays.

Cell-mediated immunity (CMI), as detected by the agarose microdroplet macrophage migration inhibition (MMI) assay, was investigated using peritoneal exudate cells (PEC) of BALB/c mice and several crude membrane (CM) and solubilized preparations of murine plasmacytomas. The MMI assay was quite sensitive and detected inhibition of macrophage migration as low as picogram quantities of CM, NP40 detergent- and papainsolubilized preparations (CS) of ADJ-PC5 and LPC-1 plasmacytomas. The data were highly reproducible from one experiment to the next with the same or different lots of the CM or solubilized extracts. Specificity studies demonstrated that ADJ-PC5 and LPC-1 plasmacytomas expressed cross-reactive tumor-associated antigens (TAA) as detected by MMI and confirmed by tumor challenge and Winn neutralization experiments. No cross-reactivity was observed with similar extracts prepared from an unrelated syngeneic simian virus 40 (SV40)-induced sarcoma. The inhibition of macrophage migration observed was mediated by culture supernatants generated from the mixture of plasmacytoma-immune spleen cells with antigens and then assayed in an indirect MMI assay on normal PEC. The agarose microdroplet MMI assay appeared to be a rapid and sensitive method to measure TAA recognition and to monitor TAA isolation and solubilization with minimum numbers of immune cells.

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Reverse transcriptase of foamy virus. Purification of the enzymes and immunological identification.

Reverse transcriptase from foamy virus, strain H4188 was estimated and purified. The enzyme has the following characteristics: 1. The reaction utilized preferentially oligo (dT) poly (rA) as a primer-template; however, the synthetic primer-template oligo (dT) poly (dA) could also be used to some extent. 2. The reaction utilized oligo (dG) poly (rC) as a primer-template with very low efficiency. 3. The crude virus preparation had a detectable endogenous reaction using the four deoxyribonucleotides for DNA polymerization. 4. The cation requirement for the enzyme reaction was much more biased for Mn++ than for Mg++ ions. 5. The molecular weight of the partially-purified enzyme was estimated to be about 80,000. Aggregates of 240,000 daltons were also seen. The activity of this enzyme was not inhibited by antisera against the reverse transcriptases of various type C RNA viruses, namely, feline endogenous leukemia virus, RD 114, Woolly simian sarcoma virus (SSV-1) and avian myeloblastosis virus (AMV). Antiserum against Rauscher leukemia virus (RLV) enzyme was marginally active against foamy virus enzyme, perhaps indicating a slight cross-reaction. The biochemical characteristics of foamy virus reverse transcriptase seemed to be very close to those of the type C RNA viruses, but the immunological reaction proved that the foamy virus reverse transcriptase was distinct from the others.

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Biologic and biochemical properties of detergent-solubilized tumor-specific transplantation antigen from a simian virus 40-induced neoplasm: brief communication.

The detergent Nonidet P40 was used to solubilize tumor-specific transplantation antigens (TSTA) from crude membranes obtained from dissociated cells of simian virus 40-induced sarcoma of BALB/c mice. A good recovery of specific tumor rejection activity was observed. One fraction, fraction V, was obtained following polyacrylamide-agarose filtration of the solubilized material, and this fraction contained most of the activity. An increased specific activity followed gel filtration. Preliminary data from lectin column chromatography of the active fraction V indicated a separation of TSTA activity from H-2 activity.

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Migration inhibition by an agarose microdroplet assay: monitoring of tumor-associated antigens on a simian virus 40-induced sarcoma.

Macrophage migration inhibition assays, with a direct agarose microdroplet method, were used to monitor TAA activity of preparations of SV-40-induced mKSA cells. These preparations included cell-free crude membranes, papain-solubilized and NP40 detergent-solubilized membrane extracts from mKSA tumor cells. The assay was extremely sensitive and could detect migration inhibition reactivity with all three types of antigenic preparations with concentrations as low at 250 ng protein/ml. The reactivities were quite reproducible from experiment to experiment using the same or different lots of these antigen preparations, and the reactivities were specific in that peritoneal exudate cells from BALB/c mice, immunized with antigenically unrelated but syngeneic plasmacytomas, were not inhibited by these antigens. The results demonstrated the usefulness of this assay in rapidly detecting small concentrations of partially purified TAA preparations by using small number of immune cells.

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