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Biomedical subjects

G Suzuki

Publications and source records attributed to G Suzuki.

At least 19 recordsLinked to original sources
PubMed1992

Irradiation increases levels of GM-CSF through RNA stabilization which requires an AU-rich region in cancer cells.

Granulocyte/macrophage colony stimulating factor (GM-CSF) is a hematopoietic growth factor that stimulates a wide range of myeloid hematopoietic cells; RNAs coding for many oncogenes and cytokines including GM-CSF have a very short half-life. The motif of AUUUA is a highly conserved sequence in the 3'untranslated regions (3'UTR) of these transcripts and is repeated a number of times in these short-lived cytokines and oncogenes. These sequences play a major role in controlling stability of these transcripts. Human cancer cells were transfected with a chimeric rabbit beta-globin gene linked to either a 58 bp sequence of the AT-rich region from GM-CSF or a control sequence. We have found that irradiation stimulates accumulation of GM-CSF, interleukin-6 (IL-6), and IL-1 beta RNAs. In addition, this accumulation of GM-CSF was at least, in part, a result of increased stabilization of GM-CSF transcripts. Further experiments showed that irradiation increased levels of the chimeric beta-globin transcripts containing AUUUA sequences from GM-CSF, but not those containing the control sequences. Our results suggest that irradiation increases expression of GM-CSF RNA and that posttranscriptional stabilization requiring AUUUA sequences probably is in part one of the mechanisms producing the increased levels of GM-CSF RNA by irradiation.

Base Sequence↗
PubMed1991

Tolerogenic ability of thymocytes in organ-cultured thymus lobes.

It is generally believed that macrophages and dendritic cells are the major cell populations that present tolerogenic self antigens to developing thymocytes. However, it is still controversial whether self antigens expressed on thymocytes themselves work as tolerogens in the thymus. To evaluate this possibility, Thy-1 bright cells were sorted out from fetal thymus cells on the 15th gestation day, and were colonized into 2'-deoxyguanosine-treated allogeneic thymus lobes. The repopulated thymus lobes were organ-cultured, and the allo-specific killer activity of thymocytes recovered from the lobes was examined. These cells were tolerant to class I but not to class II-MHC of the donor haplotype, indicating that class I molecules expressed on the thymocytes worked as tolerogen. Tolerogenic ability of Thy-1+ cells was also demonstrated in another system. Upon intimate contact with allogeneic thymus lobes on a polycarbonate filter, thymus lobes fused with each other and Thy-1+ cells co-migrated (Eur. J. Immunol. 19:1525-1530, 1989). In thymus lobes rendered parabiotic from day 5, CTL tolerance was achieved against class I but not to class II MHC. These data indicate that thymocyte-thymocyte interaction is sufficient to induce class I CTL tolerance in developing thymocytes.

Animals↗
PubMed1991

Biochemical characterization and tissue distribution of hamster complement C1s.

Several mAb (PG11, NG7, and ED4) against hamster complement C1s were obtained. PG11 and NG7 were shown to cross-react with human and rat C1s. By using an immunohistochemical method, we examined localization of C1s in tissues of hamsters and rats. Present results revealed a widespread yet specific staining of hamster C1s which is associated with endoderm-, mesoderm-, and neuroectoderm-derived cells. For example, chondrocyte of hyaline cartilage and surface epithelium of the stomach were strongly positive. Intestinal epithelium, muscle cells, pia mater and epithelium of the choroid plexus of the ventricle, and hepatocytes were also stained. The synthesis of hamster C1s in these organs was confirmed by RNA blot hybridization. Secretion of C1s into the culture medium was revealed by immunoblot analysis in cell lines of hepatocytes, kidney cells, and myoblasts of rat or hamster.

Animals↗
PubMed1990

The natural history of multiple endocrine neoplasia type 2A--a clinical analysis.

The records of 18 patients with multiple endocrine neoplasia (MEN) type 2A in a family consisting of 87 members in 5 generations, were reviewed with respect to age at onset and length of survival in a study of the natural history of this syndrome. Of these 18 patients, 8 were alive following surgical treatment, while 10 had died without treatment. The clinical onset of medullary thyroid carcinoma was noticed as a nodule in the neck at between 17 and 34 years of age (mean 24 years); the onset of pheochromocytoma was characterized by palpitation, hypertensive attacks or recurrent headache at between 17 and 42 years of age (mean 27 years); and death occurred in 10 patients at between 23 and 67 years of age (mean 40.6 years). This information on the age at onset of individual clinical manifestations, and on the length of survival of gene carriers, may be useful for clinicians who are asked to assess the risk of the development of this syndrome in a genetically predisposed asymptomatic individual, because screening tests are often refused by members of Japanese families with MEN type 2A.

Adolescent↗
PubMed1990

T cell clones are killed by a thymic stromal cell monolayer following stimulation of T cell receptor with antigen and/or H-2 molecules on the monolayer.

A thymic stromal cell clone, MRL104.8a, expressed class I and class II H-2k antigens after exposure to gamma-interferon (gamma-IFN) and produced thymic stroma-derived T cell growth factor (TSTGF) irrespective of gamma-IFN exposure. Culturing the keyhole limpet hemocyanin (KLH)-specific, I-Ek-restricted 9-16 helper T cell (Th) clone on an Ia (I-Ak and I-Ek)-expressing MRL 104.8a monolayer induced potent proliferation of the 9-16 cells by virtue of the TSTGF produced by the monolayer. In contrast, the addition of KLH to cultures resulted in lethal growth inhibition of the 9-16 Th clone. Such a phenomenon was also observed for various Th as well as cytotoxic T lymphocyte (CTL) clones, and the following were revealed: (i) the growth of the ovalbumin (OVA)-or bovine thyroglobulin (BTg)-specific Th clone on the la-expressing MRL 104.8a monolayer was also inhibited by addition of the relevant antigen. The fact that these Th clones required antigen-presenting cells (APC) capable of processing antigen for the recognition of the respective target antigen suggested the potential of MRL 104.8a cells for antigen-processing; (ii) the lethal growth inhibition of KLH-specific, I-Ak (23-1-8)- or I-Ek (9-16)-restricted Th clone was prevented selectively by anti-I-Ak or anti-I-Ek antibody respectively; (iii) the I-Ek-alloreactive Th clone (2-13) was supported for its growth on a gamma-IFN-unexposed MRL 104.8a monolayer, whereas this clone was killed on an I-Ek-expressing monolayer; and (iv) when I-Ak-reactive CTL clones were cultured on an Ia- or Ia+ monolayer, CTL clones failed to exhibit cytotoxic effect on either the Ia- or the Ia+ monolayer, but were conversely killed by the Ia+ monolayer. Its killing was also prevented by an antibody which inhibits the recognition of Ia antigen on the monolayer by CTL clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Effects of succinylcholine on serum levels of myoglobin and CK in children under halothane or enflurane anesthesia].

We studied the effects of succinylcholine (SCC) on serum levels of myoglobin (Mb) and CK in children under halothane or enflurane anesthesia. Forty-five children, aged 2 years 11 months to 12 years 6 months were subjected to this study. They were divided into four groups; the two groups were injected with SCC 1 mg.kg-1 intravenously to facilitate tracheal intubation and maintained with halothane (Group SH) or with enflurane (Group SE). The other two groups were intubated without the aid of SCC and maintained with halothane (Group H), or with enflurane (Group E). Mb was analyzed by an antibody radioimmunoassay technique and CK was analyzed by a modified Rosalki's method. While Mb increased in all four groups, the increase was pronounced in the SCC groups (60 min value of Group SH 2192 +/- 639 ng.ml-1, Group SE 1722 +/- 436 ng.ml-1, mean +/- SE), and the increase was significantly smaller in SCC free groups (Group H 40 +/- 12 ng.ml-1, Group E 43 +/- 9 ng.ml-1). The CK value increased only in the SCC groups to 174.1 +/- 32.8 IU.l-1 in Group SH, and to 193.6 +/- 35.7 IU.l-1 in Group SE at 60 min, respectively. These results indicate that increases in Mb and CK values were mainly induced by SCC injection and that SCC might play some roles in development of malignant hyperthermia.

Anesthesia, Inhalation↗
PubMed1990

[A case report of five-year survival with repeated resection of metastases from jejunal leiomyosarcoma].

A case of five-year survival of jejunal leiomyosarcoma with metastases to the liver and mesentery treated with four times surgery was reported here. Four metastatic lesions were detected in the sigmoid mesocolon once and in the liver three times and resected with hope of cure. The patient, a 37 years old male, tolerated surgical procedures including an extended right hepatic lobectomy and recovered each time. He is leading a satisfactory daily life 5 years and 3 months after the initial operation although multiple liver metastases were detected 10 months after the fourth operation. A positive surgical therapy is advocated in selected patients who have spreading leiomyosarcoma of the bowel.

Adult↗
PubMed1990

[Cell proliferation in a triple gastric cancer--a study using the isolated organ perfusion system].

So as to study the cell proliferation in a case with triple gastric cancers, we labeled an operated whole stomach with bromodeoxyuridine (BrdU) by the isolated organ perfusion system using artificial blood. Anti-BrdU immunohistochemical staining of sections from every part of the stomach was performed, and 3 separated cancerous lesions were all diagnosed as well differentiated adenocarcinomas. The labeling index (L.I.) of the cancerous lesions were found to differ from part to part. However, the L.I. tended to be higher in the superficial mucosal areas and in the cell-dense areas of the submucosa. In the almost normal fundic glands, the labeled zone was localized in the neck of the glands. The more metaplastic gastritis was advanced, the more the labeled zone shifted irregularly toward the bottom of the glands. Whenever the interstinal metaplasia was completed, the labeled zone was localized in the bottom of the glands. This method was found useful in studying the cell proliferation in the stomach without causing any harm to the human body.

Adenocarcinoma↗
PubMed1990

[A ten-year observation of malignant changes in a hyperplastic polyp of the stomach--a cellular kinetic study using bromodeoxyuridine (BrdU)].

Reported is the case of a 64 year old man with a hyperplastic polyp of the stomach that underwent malignant changes. The polyp had been followed up both endoscopically and histologically for 10 years. As it proved difficult to diagnose the malignant changes of the polyp through its endoscopic appearance, a part of polypectomized materials was studied by in vitro labeling of the S-phase cells with BrdU. Although the background hyperplastic mucosa somewhat preserved an irregular generative cell zone, the zonal distribution of the labeled cells were completely disturbed in the areas that underwent a malignant transformation, and labeled cells were often seen in the surface areas of the cancerous glands. It is important to study malignant changes in the hyperplastic polyps of the stomach from a cellular kinetic aspect.

Bromodeoxyuridine↗
PubMed1989

Effects of cyclosporine A on thymocyte differentiation in fetal thymus organ culture.

During the course of differentiation in the thymus, precursor T cells are negatively selected by a self-tolerance mechanism or positively selected to acquire restriction specificity to self major histocompatibility complexes. We investigated the process of T cell differentiation and those selections using a fetal thymus organ culture with or without cyclosporine A. The agent blocked the maturation step from CD4+8+ double positive cells to mature CD4-8+ or CD4+8- single positive cells. On the other hand, the agent did not inhibit the development of CD3+4-8- T cell receptor (TCR)alpha beta- cells, which were supposed to be T cells bearing gamma delta-TCR chains. These results suggest that the development of thymocytes bearing alpha beta- or gamma delta-TCR chains differ in requirement for thymocyte-stromal cell interaction.

Animals↗
PubMed1989

Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes.

To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC.

Animals↗
PubMed1989

Tolerance induction in the organ-cultured thymus lobes upon intimate contact with allogeneic thymus lobes.

In an organ-cultured murine fetus thymus, precursor cytotoxic T lymphocytes (pCTL) specific for alloantigens developed successfully but those reactive with self antigens were eliminated. In attempting to dissect the mechanism of self tolerance, intrathymic chimera was made by culturing two genetically disparate thymuses in close contact with each other (parabiosis of thymuses). This maneuver resulted in the induction of specific and mutual CTL tolerance. It seems that CTL tolerance was induced by clonal deletion but not by active suppression. Since 2'-deoxyguanosine treatment abolished the tolerogenic capability of the thymus, hemopoietic cells capable of migrating to and fro in the parabiotic thymuses are thought to be responsible for tolerance induction. Induction of CTL tolerance was dependent on the maturation stages of T cells in the thymus: T cells in 5-day-, but not in 7-day-cultured thymuses were susceptible to tolerance induction, indicating that T cells expressing T cell receptors at low density are susceptible to tolerance induction.

Age Factors↗
PubMed1989

Cyclosporin A and anti-Ia antibody cause a maturation defect of CD4+8- cells in organ-cultured fetal thymus.

The effects of anti-Ia antibodies and cyclosporin A (CsA) on phenotypic differentiation of murine thymocytes were assessed in organ-cultured fetal thymuses. Both agents specifically abrogated the generation of CD4+8- thymocytes. Immunohistochemical studies revealed that Ia antigen on the organ-cultured thymic epithelial cells did not disappear with the addition of the agents, although anti-Ia antibody was proved to bind to Ia antigen during the culture. On the other hand, CsA neither changed the expression of Ia nor bound to it. As CsA is known to block the signalling cascade initiated by perturbation of T-cell receptor (TcR), it is suggested that both the Ia expression in the thymus and the signalling via receptors on thymocytes, the signals presumably generated by TcR binding to class II MHC molecules, might be necessary for phenotypic differentiation of class II MHC-restricted T cells (CD4+8- cells), but not for class I MHC-restricted T cells (CD4-8+).

Animals↗
PubMed1989

[Laboratory and clinical studies on cefteram pivoxil in pediatric field].

Pharmacokinetic and clinical studies of cefteram pivoxil (CFTM-PI, T-2588) fine granules in children were performed and the following results were obtained. 1. Peak serum concentrations in 4 children given orally a dose of 3 mg/kg and 2 children given orally a dose of 6 mg/kg after meal were reached in 3 to 4 hours and the concentration curves were dependent on dosage levels. The urinary recovery rates up to 8 hours were 29.7% in children given a dose of 3 mg/kg and 29.7% in children given a dose of 6 mg/kg. 2. Clinical efficacies were evaluated in 38 patients with bacterial infections. Twenty seven patients were given each doses of 3 mg/kg in 3 times a day and other 11 patients each doses of 6 mg/kg in 3 times. Clinical effects of CFTM-PI were excellent in 18, good in 19, fair in 1 case, hence the overall clinical efficacy rate was 97.4%. 3. Bacteriologically, 24 strains of causative organisms were isolated. The overall bacteriological eradication rate was 81.8%. Antimicrobial activities were excellent especially against Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae. 4. As for the side effects, slight loose stools were observed in 2 cases, and in laboratory tests, elevations of GOT and GPT were observed in 1 case and an elevation of eosinophil was observed in 1 case. But no one needed any treatment. 5. CFTM-PI is a useful and safe oral antibiotic for the treatment of bacterial infections in pediatrics.

Bacterial Infections↗
PubMed1988

Antigen-induced suppression of the proliferative response of T cell clones.

Proliferation of Ag-specific T cell clones can be inhibited by the addition of high concentrations of Ag at the beginning of culture. Under these conditions the cells produce lymphokines and express high affinity IL-2R but fail to divide, even after the addition of exogenous IL-2. This state results from restimulation of the cells with Ag-Ia molecule complexes approximately 20 h after initiation of culture. It can be prevented by addition of either an anti-Ia or an anti-L3T4 mAb at that time, but not by cyclosporin A, and mimicked in cultures containing low concentrations of antigen by addition at that time of high Ag concentrations or normal stimulatory concentrations of Con A. These observations suggest that restimulation of activated T cell clones 20 h after their initial stimulation prevents them from dividing.

Animals↗