Biomedical subjects
T Natori
Publications and source records attributed to T Natori.
[Transplantation and immunity].
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Leukocyte subsets infiltrating fully allogeneic, long-surviving rat liver allografts.
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Detection of a serum class I molecule in rat with anti-rat liver beta-2-microglobulin.
Rat serum was fractionated on a column of Sephacryl-300 and tested with a rabbit anti-rat beta-2-microglobulin (B2m) antiserum. This antiserum was directed against B2m purified from rat liver, and its specificity was confirmed by immunoprecipitation procedures. The antiserum recognized three peaks in the fractionated rat serum: a 200- to 300-kd (kilodalton) fraction, a 40- to 70-kd component, and the free 12-kd B2m. Indirect immunoprecipitation from the 200- to 300-kd fraction led to the identification of a 43-kd polypeptide associated with B2m. A xenoantiserum against RT1 class I antigen also precipitated a similar polypeptide from the same fraction, but this molecule differed in size and antigenic specificity from the one precipitated by anti-rat B2m.
A study on class II antigens involved in the T cell proliferative responses to PPD using cross-reacting monoclonal antibodies in human and murine system.
Two monoclonal antibodies (MoAb) 1E4 and ISCR3, which detect class II antigens across species barriers, were studied for their inhibitory effects on human and murine T cell proliferative responses to purified protein derivative of tuberculin (PPD). The 1E4 detected at least a polymorphic determinant on I-A molecules from mice carrying the H-2b haplotype, and the ISCR3 detected the Ia.7 determinant on I-E molecules. Nevertheless, both 1E4 and ISCR3 recognized monomorphic determinants on HLA-DR antigens (human I-E equivalent molecules), but not on HLA-DQ antigens (human I-A equivalent molecules). It was demonstrated that 1E4 significantly inhibited PPD-specific responses of T cells from Ib-bearing mice. In contrast, ISCR3 showed marginal effects on the responses of mice bearing Ia.7. However, in the human system both 1E4 and ISCR3 reduced proliferative responses to PPD. These results suggest that a functional difference exists between humans and mice in the I subregion products involved in the T cell proliferative responses to PPD.
A monoclonal antibody (1B7) specific for polymorphic determinant on mouse I-A antigens recognizes monomorphic epitope shared by most of RT-1 haplotypes in rats.
A monoclonal antibody, 1B7, which was established by immunizing C57BL/10 mice with splenocytes from B10.BR, was investigated by serological, immunochemical and functional analyses in mouse, rat, guinea pig and human systems. 1B7 recognized a polymorphic determinant on class II antigens in the mouse system. In the rat system, however, this antibody appeared to recognize a monomorphic epitope shared by all RT-1 haplotypes. 1B7 showed no reactivity in the human and guinea pig strains tested.
Intra-cholecystic ectopic liver.
A 56-year-old Japanese woman who had an ectopic liver attached to the inner surface of the gallbladder is reported. The ectopic nodule measuring 1.2 X 0.5 X 0.8 cm was found incidentally when her gallbladder was resected because of cholelithiasis. Ectopic liver tissue in reported cases war located on the serosal surface, or in the wall of the gallbladder. This report described, to our knowledge, the first case of an ectopic liver nodule attached to the mucosal surface of the gallbladder with a thin pedicle.
An AFP-producing gastric carcinoma with features of hepatic differentiation. A case report.
A patient with primary gastric adenocarcinoma with extremely high serum alpha-fetoprotein (AFP) levels (12,000 ng/ml) is described. Histologically, foci strongly resembling hepatocellular carcinoma with hyaline globules were noted. Within tumor cells, AFP was identified with both light and electron microscopy, showing the production of AFP by tumor cells themselves. Furthermore, 88% of serum AFP combined with Concanavalin A (ConA), revealing that it was hepatic-type AFP and not germ-cell-type. Localization of alpha-1-antitrypsin within tumor cells was also noted. Ultrastructural study showed that there were two types of structures corresponding to periodic acid-Schiff (PAS)-positive globules, one of which, the proteinaceous material in intracytoplasmic lumina, was found to contain AFP. Among gastric adenocarcinomas with a high serum AFP level (several thousand or more ng/ml of AFP), foci resembling hepatocellular carcinomas have been reported by several investigators. Those gastric carcinomas, together with the current case, may constitute a clinicopathologic entity, hepatoid adenocarcinoma of the stomach.
The RT1.B/D-region products defined by rat monoclonal alloantibodies.
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Nonphagocytotic, Ia-bearing cells of host origin in acutely rejected rat renal allografts.
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The effect of RT1 subregion differences on liver allograft survival in the rat.
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Coexistence of stomach cancer and renal adenoma in renal allograft. Clinical and autopsy findings and a review of previous cases in Japan.
Autopsy findings of a 34-year-old Japanese male with stomach cancer in a renal allograft are presented. The renal graft was given by his 53-year-old mother, who had the same HLA type as the patient and showed negative response in the Mixed Leukocyte Culture Reaction test. Stomach cancer occurred 4 years and 5 months after the renal graft, and infiltrated widely into the abdominal cavity, causing rectal stricture. In his original left kidney, a small renal adenoma was found. The tumor cells of the adenoma were composed of clear cells. In the adenoma, infiltration of stomach cancer was found. The renal allograft functioned very well until his death in spite of several rejection episodes. This is the seventh reported case in Japan in which a renal allotransplant was accompanied by malignancies.
Low responsiveness to MLM bacilli associated with an impaired macrophage function in CBA/J mice.
It has previously been reported that susceptibility to Mycobacterium lepraemurium (MLM) infection (subcutaneous inoculation) differs markedly between CBA/J and C57BL/6 mice. The high susceptibility of CBA/J mice was shown to be due to the generation of cyclophosphamide-sensitive, I-Jk-positive suppressor T cells. In the present study, we attempt to show functional differences between splenic macrophages of both strains of mice in terms of their phagocytic and antigen-presenting activities against MLM bacilli. The results show that (a) the secondary MLM-induced T-cell proliferative response is dependent on Ia-positive antigen-presenting cells (APC), (b) macrophages of CBA/J mice are able to present antigens to F1 T cells, and yet (c) they show an extremely low phagocytic activity, (d) antigen presentation by APC of CBA/J mice lasted for a longer period than that of C57BL/6 mice after MLM infection. These results suggest that there is a functional difference in CBA/J and C57BL/6 APC, which could account for the phenotypic difference in immune responsiveness to MLM bacilli.
Different distributions of T cell subsets between perivascular and interstitial peritubular areas during rejection of rat renal allografts: a quantitative and ultrastructural study using monoclonal antibodies.
Distributions and ultrastructures of T cell subsets within grafts were studied in unmodified, first-set rat renal transplantation systems (F344----WKA, TO----WKA). Rejections took place within 9.0 +/- 0.5 and 12.2 +/- 1.6 days, respectively. Mouse monoclonal antibodies, R1-3B3 and R1-10B5, were used here for the detection of RLyt-1 and RLyt-2 antigenic systems of rat T cells, respectively. RLyt-1 and RLyt-2 antigens are chemical homologues of mouse Lyt-1 and Lyt-2,3 antigens. In the perivascular areas, RLyt-1+,2- cells were the predominant T cells in earlier stages of rejection. However, toward the end of rejection, RLyt-1+,2- cells decreased in number, with the increase in RLyt-1+,2+ cells. In the interstitial peritubular areas, RLyt-1+,2+ cells were the predominant T cells throughout the course of rejection. Thus, the major T cells in perivascular areas were helper T cells in earlier stages and cytotoxic/suppressor T cells in the later stage, whereas in interstitial peritubular areas, cytotoxic/suppressor T cells were the major T cell population during the entire course of rejection. Ultrastructural studies revealed that many RLyt-2+ blast cells had clustered dense bodies, and that RLyt-2+ cells were found among renal tubular epithelial cells. Renal tubular cells adjacent to RLyt-2+ cells were degenerative in most cases. In addition, membranous structures seen in grafts were RLyt-1+,2+,Ia-, suggesting that they might derive from the destruction of cytotoxic/suppressor T cells after several target cell lyses in vivo.
RT1-linked Ir and Is genes control the immune response to bovine insulin in the rat.
The immune response to bovine or pork insulin (BI or PI, respectively) was studied in the rat using the in vitro insulin-induced lymphocyte-proliferation assay. Results indicated that 11 inbred rat strains were divided into categories of high and low responders. Two high responders, SDJ (RT1u) and BN(RT1n) inbred rat strains, appeared to recognize different antigenic determinant(s) on the insulin molecule. The results of linkage and segregation analyses in F1, F2, backcross, and partially congenic rats showed that the Ir gene (Ir-BI), which encodes the high responsiveness in the SDJ rats, is inherited associated with RT1u, whereas the immune suppression gene (Is-BI), which encodes the low responsiveness in the WKA(RT1k) rats, is inherited together with RT1k. The Is-BI is the first major histocompatibility complex (MHC)-linked Is gene reported in the rat. The LEJ(RT1-AuBb) inbred rat strain showed a low response to BI, indicating that Ir-BI is closer to RT1-B/RT1-D region than to RT1-A.
Immunochemical evidence for multiple beta units of the class II molecule in the rat.
The RT1-B/D region-associated antigens which were serologically defined in the previous study (Ohhashi et al., 1981), were partially purified from membranes of a rat B cell leukaemia, KNL-14. Sequential immunoprecipitation test, with the partially purified 125I-B/Dak preparation using four different rat alloantisera, including a monoclonal antibody, disclosed three distinctive populations of beta units of the class II molecules. Highly purified beta units of three discriminable class II molecules were shown to have different structural properties in terms of molecular weights and of electrophoretic profiles on the isoelectric focusing. The beta units shifted to a position of higher molecular weight on SDS-PAGE under reducing condition, thus suggesting to carry intradisulfide bonds. Furthermore, the highly purified beta units cross-reacted with murine anti-Ia sera. The rebinding test revealed that at least two discriminable species of beta units cross-react with anti-I-Ak monoclonal antibody, whereas beta units purified by binding with the 1E4 monoclonal antibody cross-reacted with anti-I-Ab and/or anti-I-Ad antiserum. On the basis of structural and antigenic properties, we have postulated that the rat class II region can be divided into at least three subregions, each containing a locus which encodes a distinctive beta unit of the class II molecule.
Primary yolk sac tumor of the liver. An autopsy case with ultrastructural and immunopathological studies.
An autopsy case of yolk sac tumor of the liver in a 29-year-old female was reported. The tumor was found originally in the right anterior segment of the liver on the first operation. The autopsy disclosed that the liver was almost entirely replaced by multiple, round tumor nodules. The tumor masses continuously extended to the peritoneum and to the subcutaneous tissue. There were no tumors in other organs including the ovaries, gut, stomach, lung, uterus, and kidneys, indicating that the tumor originated in the liver. Microscopically, the tumor showed typical characteristics of the yolk sac tumor. An immunohistochemical study showed that AFP was distributed fine granularly in the cytoplasm of tumor cells. Electron microscopic observation disclosed large amounts of electron-dense material being closely related to basement membrane.
[Analysis of natural anti-tumor antibody carrying a cross-reactive idiotype 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 shows to be specific for Fab fragments by immunoelectrophoresis. Furthermore, four lines of evidence supported 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 pI 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 (FrII) were shown to have enhancing activity of the tumor growth when they were injected into syngeneic animals. Whereas Fab-free fractions that were separated from the Fab fragments by column electrophoresis showed no enhancing activity. These results suggested strongly 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 were discussed.