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T Sudo

Publications and source records attributed to T Sudo.

At least 145 records · Page 8Linked to original sources
PubMed1991

Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture.

We have examined the effects of a stromal cell-derived cytokine designated interleukin 11 (IL-11) on the proliferation of murine hemopoietic progenitors in methylcellulose culture. COS cell-conditioned medium containing IL-11 supported formation of granulocyte/macrophage colonies and a small number of multilineage colonies including blast cell colonies in cultures of marrow cells from normal mice. When tested with marrow cells harvested 2 days after injection of 5-fluorouracil at 150 mg/kg, IL-11 enhanced interleukin 3-dependent colony formation, whereas IL-11 alone supported only scant colony formation. Serial observations (mapping studies) of cultures of post-5-fluorouracil spleen cells indicated that the mechanism of the synergistic effect of IL-11 is to shorten the dormant period of stem cells, an effect very similar to that of interleukin 6. When pooled blast cells were plated into medium containing IL-11 and erythropoietin, only macrophage colonies were observed. Thus, IL-11 can directly support the proliferation of committed macrophage progenitors and, and like interleukin 6 and granulocyte colony-stimulating factor, act synergistically with interleukin 3 to shorten the Go period of early progenitors.

Animals↗
PubMed1991

The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione.

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.

Adult↗
PubMed1991

3-O-alkylascorbic acids as free-radical quenchers: synthesis and inhibitory effect on lipid peroxidation.

A novel series of 3-O-alkylascorbic acids (3-RASA, 3a-n) was synthesized to act as radical scavengers for active oxygen species and free radicals, and their redox potentials and inhibitory effects on lipid peroxidation in rat liver microsomes were evaluated. The redox potentials of the 3-RASA compounds were increased by the substituent group to 90-190 mV above the potential for ascorbic acid (i.e., 3-RASA compounds were harder to oxidize). Although 3-O-dodecylascorbic acid (3c) and 3-O-(decylcarbomethyl)ascorbic acid (3i) differed in their redox potentials, they both markedly inhibited lipid peroxidation in rat liver microsomes to a similar extent (IC50 = 3.1 and 3.3 X 10(-6) M, respectively). Structure-activity relationship studies demonstrated that the anti lipid peroxidation activity of the 3-RASA compounds was markedly dependent upon their hydrophobicity.

Animals↗
PubMed1991

High-molecular-weight Ly-5 isoforms expressed on T cells: activation-dependent expression.

Interleukin 2 (IL-2)-dependent granular T lymphocyte (GTL) lines derived from murine spleen were shown to express a Ly-5 antigen with the so-called 'B220-epitope' recognized by 6B2 mAbs, which were normally exhibited on B-lineage cells. Immunoprecipitation analysis revealed that the Ly-5 isoform on GTL lines represented the highest-molecular-weight Ly-5 so far described (260 kd), distinct from the B220 isoform on a pre-B cell line (240 kd). The size difference between them was also evident after the endoglycosidase treatment (210 versus 190 kd), strongly suggesting that these Ly-5 isoforms had core proteins of distinct size. Sequential immunoprecipitation by 6B2 and 14.8 mAbs further indicated that the 260 kd Ly-5 on GTL lines predominantly expressed '6B2 epitope' while '14.8 epitope' dominated in the B220 (240 kd) on a pre-B cell line. Northern blot analysis of the Ly-5 transcripts using probes for the known alternative exons failed to show any evidence for mRNA of the 260 kd Ly-5 distinct from that of B220. Polymerase chain reaction analysis, however, suggested that the 260 kd isoform mRNA might be transcribed from a distinct promoter with a yet undefined exon(s). The 6B2+ Ly-5 isoform was hardly detected on normal splenic T cells, but was shown to be induced rapidly on the majority of T cells following IL-2 stimulation in vitro, indicating that this particular Ly-5 isoform behaved as an 'activation antigen' on T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interleukin 7 preferentially supports the growth of gamma delta T cell receptor-bearing T cells from fetal thymocytes in vitro.

Murine fetal thymus cells were cultured with various interleukins (IL-1, 2, 3, 4, 5, 6, and 7) in the absence or presence of phorbol 12-myristate 13-acetate (PMA), and it was found that only IL-4 and IL-7 induced a prominent proliferative response in the presence of PMA. A large proportion of cells grown in the cultures of fetal thymus cells (days 15 and 17 of gestation) stimulated with PMA plus IL-4 or with PMA plus IL-2 remained CD4-CD8-. In marked contrast, nearly 70% of the cells generated in the cultures of the same fetal thymocytes stimulated with PMA plus IL-7 expressed CD8 on their surface. Approximately 30% of these cells expressed TCR gamma, delta, whereas TCR alpha beta+ cells were virtually undetectable. The cells grown in cultures stimulated with PMA plus IL-7 comprised three populations: CD4-Lyt-2-3-, CD4-Lyt-2 + Lyt-3- and CD4-Lyt-2 + Lyt-3+, and that TCR gamma delta+ T cells were found in all three populations. It was also found that the addition of IL-7 in the culture of adult CD4-CD8- thymocytes on the monolayer of a thymic stromal cell line, which selectively promotes the generation of alpha beta T cells, resulted in the generation of gamma delta T cells. These results strongly suggest that IL-7 plays an important role in the development of gamma delta T cells.

Animals↗
PubMed1991

Generation of functional murine macrophage lines employing a helper-free and replication-defective SV40-retrovirus: cytokine-dependent growth.

By using a helper-free and replication-defective recombinant retrovirus encoding the SV40 early antigens (MV40), we have established continuous macrophage (M phi) lines. All of the lines were nonproducer M phi's with differentiated M phi functions such as phagocytosis, cytotoxicity, and IL-1 and TNF production. To determine the effects of several cytokines on growth of mature M phi's, the responsiveness of these established M phi lines to various cytokines was investigated in methylcellulose culture. Their response patterns to several cytokines alone and in combination were different, implying that there might be mature M phi subpopulations with distinct growth profiles regulated by several cytokines. On the other hand, all of the lines efficiently yielded a number of colonies in response to interleukin-4 (IL-4) alone. Moreover, IL-4 cooperated with interleukin-3 (IL-3) to enhance colony formation of all the lines. A similarly synergistic effect was observed in combination of IL-4 and macrophage-colony stimulating factor (M-CSF) in almost all the lines. Similar results were obtained with colony formation of fresh thioglycolate-induced M phi's. These observations suggested that IL-4 was involved in growth of mature M phi's. Our present results suggest that the helper-free and replication-defective MV40 is of use to obtain continuous and functional cell lines from primary M phi's.

Animals↗
PubMed1991

3-O-alkylascorbic acids as free radical quenchers. II. Inhibitory effects on some lipid peroxidation models.

We previously found that 3-O-dodecylcarbomethylascorbic acid (3-RASA,3,HX-0112) exhibited a potent inhibitory effect on biochemical lipid peroxidation and that 3-RASA (3) alleviated myocardial lesions induced by ischemia-reperfusion treatment in rats. In this study we examined the mode of action of 3-RASA (3) on the inhibition of lipid peroxidation. There was no reducing activity by 3-RASA (3) (i.e., no oxide was produced) against ferric ions and superoxide anion radicals. The low reducing activity of 3-RASA (3) against a radical as compared to that of alpha-tocopherol was obtained by using a stable radical. However, 3-RASA (3) had a potent inhibitory effect, almost equal to that of alpha-tocopherol, in the model of lipid peroxidation dependent on enzymatic superoxide generation. 3-RASA (3) very strongly inhibited the chain-reaction of the peroxidation induced by Fe(2+)-linoleic acid hydroxyperoxide. On the basis of these findings, it appears that the anti-lipid-peroxidative effects of 3-RASA (3) are due to the inhibition of the radical chain-reaction, as a chain-breaking antioxidant.

Ascorbic Acid↗
PubMed1991

Expression of the CRE-BP1 transcriptional regulator binding to the cyclic AMP response element in central nervous system, regenerating liver, and human tumors.

CRE-BP1 is a transcriptional regulator binding to the cyclic AMP response element (CRE). To understand the role of CRE-BP1 in vivo, we studied the expression of the CRE-BP1 gene in monkey tissues including the central nervous system, in rat regenerating liver, and in human cancer tissues compared with normal tissues. The CRE-BP1 mRNA was detected in all tissues examined, and was fairly abundant in brain. The CRE-BP1 mRNA was expressed in monkey brain tissues with different region specificities. In the hippocampus, frontal lobe, and parietal lobe, the CRE-BP1 mRNA was abundant and two mRNA species 4.0 kb and 3.7 kb in length were expressed. In rat liver, the expression of the CRE-BP1 gene was increased up to 4- to 5-fold of the normal level within 12-24 h after partial hepatectomy. Furthermore, the levels of CRE-BP1 mRNA in some clinical samples of human tumors were apparently higher than that in normal tissues. These results suggest that CRE-BP1 may be important for both the signal transduction in brain and cellular proliferation.

Animals↗
PubMed1991

Spontaneous rupture of hepatocellular carcinoma: a review of 172 Japanese cases.

The spontaneous rupture of a primary hepatocellular carcinoma (HCC) accounts for 10% mortality of HCC patients in Japan. Because this problem occurs much less frequently in western countries, it is often difficult for clinicians practicing in such countries to decide upon the best course of action during the crisis accompanying the spontaneous rupture of a HCC. In an effort to advance the general knowledge of this disease and clarify a selection for its treatment, we review 172 cases of spontaneous rupture of a HCC reported in the Japanese literature. The chief complaint of the patients was sudden epigastralgia or right hypochondriac pain. Abdominal paracentesis was positive in 86% of the patients. Liver failure was the cause of death in 42% of the patients. Therefore, it is important to evaluate liver reserve quickly. In addition, emergency hemostatic procedures must be implemented to avoid hemorrhagic shock. Although two-stage hepatectomy was performed in only 12% of the cases, these had the highest survival rates. Consequently, this is the procedure of choice for the treatment of spontaneous rupture of a HCC.

Adult↗
PubMed1991

Characterization of the promoter region of the c-yes proto-oncogene: the importance of the GC boxes on its promoter activity.

In this study we cloned the 5' flanking sequence of the human c-yes gene and identified its promoter region. A 0.53 kilobase pair (kbp) fragment containing the 5' terminus of the c-yes gene showed strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected into monkey CV-1 cells. By nuclease S1 mapping multiple transcriptional start sites were detected within the promoter region. Nucleotide sequence analysis revealed that the c-yes promoter region had high G + C contents (64%) and contained six GC box-like sequences (one at the 5' distal region and five in a cluster at the 5' proximal region), but not a TATA box. These features of the c-yes promoter region are similar to those of other protooncogenes, ras-family genes and c-raf-1, and some house-keeping genes. Deletion analysis suggested that the most downstream 0.21 kbp region is primarily important for the promoter activity. This 0.21 kbp region contains one major and another minor transcriptional start site. Five GC box-like sequences were located within this region, and four of them were shown to bind with purified Sp1 transcription factor. Furthermore, using the base-substituted mutants of the Sp1-binding sites, each GC box in the cluster (GC1 to GC4) was shown to affect the c-yes gene expression.

Animals↗
PubMed1991

[Histochemical changes of islet cells of Langerhans after hepatectomy and effect of glucagon and insulin].

It has been made by a number of studies that after hepatic resection, portal factors such as insulin and glucagon play an important role in liver regeneration. We have reported hypertrophy of Langerhans islands of dogs after partial hepatectomy. In the present study we attempted to clarify the mechanism of this hypertrophy. In a control group, a forty-percent hepatectomy was carried out. One and four weeks after surgery, 0.5g/kg of glucose was administered intravenously followed by a blood sampling from the portal vein to measure the changes of glucose, insulin and glucagon respectively. In addition area changes of the islets of Langerhans after the operation were measured with PAP technique. In a GI group, the same experiment as in the control group was done and 1mg of glucagon and 2IU/kg of insulin were administered every morning after the operation. The following results were obtained. In the GI group, there were no decrease in portal plasma insulin level and no enlargement of the sizes of the islets four weeks after surgery.

Animals↗
PubMed1990

[A case of prolonged jaundice after surgical treatment of obstructive jaundice caused by a carcinoma of the head of the pancreas relieved with dibutyryl cyclic AMP].

Recently, we experienced a case of obstructive jaundice caused by a carcinoma of the head of the pancreas which could not be relieved by reduction surgery. The operation performed was a cholecystectomy and supraduodenal choledochotomy with T-tube insertion. Glucagon and insulin were, therefore, administered with the aim towards the recovery of the liver function to be induced by the enhancement of the liver regeneration. The treatment, however, was not effective. Then, dibutyryl cyclic AMP was administered to the case by intravenous drip infusions at the rate of 5 micrograms/kg/min. Thereafter, the value of serum total bilirubin was reduced remarkably. A prolonged and intense obstructive jaundice is generally accompanied by damage to the liver function, and the condition carries a high risk of postoperative complication. In this paper, the effectiveness of dibutyryl cyclic AMP on liver cell damage caused by prolonged obstructive jaundice are reported.

Aged↗
PubMed1990

Granulocyte-macrophage colony-stimulating factor enhances macrophage accessory function in con A-stimulated T-cell proliferation.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to augment various macrophage (M phi) functions, including antigen presentation in the antibody-producing response. We investigated the augmentative effect of GM-CSF on M phi A-cell activity in concanavalin A-stimulated T-cell proliferation. Pretreatment with GM-CSF of peritoneal M phi enhanced the T-cell proliferative response. This effect of GM-CSF was dose dependent and GM-CSF supplementation was needed at the beginning of M phi culture. We observed that GM-CSF induced M phi spreading and firm attachment accompanied with enlargement of the cytoplasm, but could not induce de novo expression of Ia antigen. GM-CSF treatment enabled M phi to produce more interleukin (IL)-1 and IL-6 upon stimulation with lipopolysaccharides or polyinosinic-polycytidylic acid, but was unable to stimulate M phi directly. This was confirmed by Northern blot analysis. These results indicate that GM-CSF augments M phi A-cell activity through the enhancement of the capacity of M phi to produce IL-1 and IL-6.

Animals↗
PubMed1990

Promoter region of the human CRE-BP1 gene encoding the transcriptional regulator binding to the cyclic AMP response element.

Genomic clones containing the 5'-terminal portion of the human CRE-BP1 gene that encodes transcriptional regulator binding to the cyclic AMP response element (CRE) were isolated. Multiple transcriptional start sites in the promoter region were identified by nuclease S1 mapping and primer extension analysis. By DNase I footprinting with use of purified transcription factor Sp1 and nuclear extracts prepared from HeLa cells, 11 Sp1-binding sites, two CCAAT sequences, two CREs, and three unknown factor recognition elements were found. Transfection of chimeric chloramphenicol acetyltransferase plasmids containing various deletions of the promoter into CV-1 cells indicated that the region between nucleotides -50 and 90, which contained three Sp1-binding sites and one CRE, was sufficient for basal promoter activity. These results suggest that multiple sequence-specific DNA-binding proteins may control the expression of the CRE-BP1 gene, although Sp1 seems to be important for the basal promoter activity.

Base Sequence↗
PubMed1990

Production and characterization of monoclonal antibodies against rat platelet GPIIb/IIIa.

Four murine monoclonal antibodies against rat platelets were produced by fusion of spleen cells from mice intravenously immunized with whole rat platelets. All four antibodies immunoprecipitated two major platelet membrane proteins with apparent molecular weights of 130,000 and 82,000 (nonreduced) and of 120,000 and 98,000 (reduced), which were structurally analogous to human glycoprotein (GP) IIb/IIIa, i.e. rat GPIIb/IIIa. Two of four antibodies, named P9 and P55, strongly inhibited adenosine diphosphate (ADP)-induced aggregation of washed rat platelets and caused approximately 50% inhibition of human fibrinogen binding to ADP-stimulated rat platelets, suggesting that rat GPIIb/IIIa serves as a fibrinogen receptor in ADP-induced aggregation. In contrast, two other antibodies, named P14 and P34, themselves caused aggregation of rat platelets in platelet-rich plasma (PRP) and the secretion of 14C-serotonin from 14C-serotonin-labeled PRP. These results indicate that rat GPIIb/IIIa plays an important role in platelet aggregation.

Adenosine Diphosphate↗
PubMed1990

The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene.

Mice homozygous for the recessive mutation osteopetrosis (op) on chromosome 3 have a restricted capacity for bone remodelling, and are severely deficient in mature macrophages and osteoclasts. Both cell populations originate from a common haemopoietic progenitor. As op/op mice are not cured by transplants of normal bone marrow cells, the defects in op/op mice may be associated with an abnormal haematopoietic microenvironment rather than with an intrinsic defect in haematopoietic progenitors. To investigate the molecular and biochemical basis of the defects caused by the op mutation, we established primary fibroblast cell lines from op/op mice and tested the ability of these cell lines to support the proliferation of macrophage progenitors. We show that op/op fibroblasts are defective in production of functional macrophage colony-stimulating factor (M-CSF), although its messenger RNA (Csfm mRNA) is present at normal levels. This defect in M-CSF production and the recent mapping of the Csfm structural gene near op on chromosome 3 suggest that op is a mutation within the Csfm gene itself. We have sequenced Csfm complementary DNA prepared from op/op fibroblasts and found a single base pair insertion in the coding region of the Csfm gene that generates a stop codon 21 base pairs downstream. Thus, the op mutation is within the Csfm coding region and we conclude that the pathological changes in this mutant result from the absence of M-CSF.

Amino Acid Sequence↗
PubMed1990

Stepwise progression of B lineage differentiation supported by interleukin 7 and other stromal cell molecules.

Growth of early B precursor cells was investigated in vitro by using rIL-7 and IL-7-defective stromal cell line PA6 as separate growth signals. B cell development proceeds through three sequential stages different from the growth signal requirement. The cells in the first stage require PA6 alone for the proliferation, and differentiate into the second stage, which requires both PA6 and IL-7 for its growth. When IL-7 is available for the cells in the second stage, they proliferate extensively on the PA6 layer, and some acquire the ability to proliferate in response to IL-7 alone. This sequential change of growth signal requirement, however, does not proceed autonomously along the time schedule. The possibility that it is primarily directed by the result of Ig gene rearrangement is considered. This mode of growth control may explain why only functional B cells are selected in the error-prone process of Ig gene rearrangement during B lineage differentiation.

Animals↗