[Anti-thrombogenicity of recombinant human thrombomodulin-- ex vivo anti-thrombogenicity and its application to medical materials].
Explore the source record for details and available documents.
Antithrombin III↗
Biomedical subjects
M Akashi
Publications and source records attributed to M Akashi.
Role of AUUU sequences in stabilization of granulocyte-macrophage colony-stimulating factor RNA in stimulated cells.
RNAs for transiently expressed genes such as oncogenes and cytokines, including granulocyte-monocyte colony-stimulating factor (GM-CSF), have a short half-life (T1/2). A cluster of AUUU sequences identified in the 3' untranslated (UT) region of these RNAs has been implicated in controlling stability of these transcripts. We examined the role of AUUU sequences in mRNA stability of GM-CSF after stimulation of cells. Human fibroblasts (W138) were stably transfected with chimeric constructs containing the beta-globin gene linked to a 52-bp tail of GM-CSF containing either eight ATTTT (pNEOR beta G-AT) or eight repeats in which the AT sequences have been changed to GC sequences (pNEOR beta G-GC). Data confirmed that AUUU sequences in 3'UT region of GM-CSF play a major role in GM-CSF RNA instability. Stimulators of protein kinase C (PKC), cycloheximide (CHX), sodium fluoride (NaF), and, to a more limited extent, interleukin-1 beta (IL-1 beta), appear to stabilize GM-CSF RNA through these AUUU sequences, but tumor necrosis factor-alpha (TNF-alpha) induces stabilization of GM-CSF RNA through a mechanism independent of their AUUU sequences.
Base Sequence↗
Development of a novel 1,25(OH)2-vitamin D3 analog with potent ability to induce HL-60 cell differentiation without modulating calcium metabolism.
We describe several novel analogs of the seco-steroid 1,25(OH)2-vitamin D3[1,25(OH)2D3] and their effects on differentiation and proliferation of HL-60 human myeloid leukemic cells in vitro as well as their effects on calcium metabolism in vivo. The 1 alpha-25(OH)2-16ene-23yne-26,27F6-vitamin D3 is the most potent analog reported to date, having about 80-fold more activity than the reference 1,25(OH)2D3 for inhibition of proliferation and induction of differentiation of HL-60 cells. Also, this analog decreased RNA expression of MYC oncogene in HL-60 by 90% at 5 x 10(-10) mol/L. Intriguingly, intestinal calcium absorption and bone calcium mobilization mediated in vivo by 1 alpha-25(OH)2-16ene-23yne-26,27F6-D3 was found to be markedly (15-fold) less than that of 1,25(OH)2D3. In addition, 1 alpha-25(OH)2D3 bound to 1,25(OH)2D3 receptors of both HL-60 and intestine more avidly than did 1 alpha-25(OH)2-16ene-23yne-26,27F6-D3. This novel analog may open up new therapeutic strategies for several hematopoietic, skin, and bone abnormalities and may provide a new tool to understand how vitamin D3 seco-steroids induce cellular differentiation.
Bone Marrow↗
Production of islet cell antibodies from Epstein-Barr virus-transformed peripheral blood lymphocytes in type 1 (insulin-dependent) diabetic patients.
Islet cell antibodies are usually detected in the sera of almost all Type 1 (insulin-dependent) diabetic patients within several months after onset of the disease. The antibodies then disappeared quite early during the course of the disease. The present study was undertaken to detect islet cell antibody-producing clones in peripheral blood lymphocytes of Type 1 diabetic patients whose islet cell antibodies could not be detected in sera. Epstein-Barr virus-transformed lymphocytes were employed to enhance the production of antibodies and to detect the clones from peripheral blood lymphocytes. Peripheral blood lymphocytes were obtained from 40 islet cell antibody-negative Type 1 diabetic patients, 10 antibody-positive Type 1 diabetic patients, 30 Type 2 (non-insulin-dependent) diabetic patients and 40 normal control subjects. Epstein-Barr virus-transformed lymphocytes were cultured for 4 weeks and the culture supernatants were used for assay of islet cell antibodies. Islet cell antibody assays were performed by immunohistochemical methods using peroxidase-labelled protein A for IgG antibodies, peroxidase-labelled anti-human IgM antibodies for IgM antibodies and fresh frozen human pancreatic tissue. IgG-islet cell antibodies were detected in 26 islet cell antibody-negative patients (65%), eight antibody-positive patients (80%) and one Type 2 diabetic patient (3%) in the culture supernatants. Islet cell antibodies in the supernatants could not be detected in any of the control subjects. IgM-islet cell antibodies could not be detected in any of the patients or control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Autoantibodies↗
Peripheral vascular permeability following a thermal injury to the airway.
Effects of thermal injury to the airway on the vascular permeability in the region of head and neck, were studied in the canine models. The thermal airway injury was produced by an inhalation of a gas burner's flame through the metallic tracheostomy cannula. The changes in vascular permeability were evaluated by calculating the reflection coefficient, which was obtained by the protein washdown technique into lymph. The reflection coefficient after the flame inhalation did not show any increases, while it increased significantly after a histamine infusion into the carotic artery. We concluded, that the vascular permeability in the unburned area does not increase at least in the first 3 hr after a thermal injury to the airway.
Journal Article↗
D-factor: modulation of expression in fibroblasts.
Differentiation inducing factor (D-factor) is a recently described protein. The gene has been cloned, but little is known concerning regulation of expression of the gene. Our study showed that fibroblasts from a variety of tissues (lung, bone marrow, gingiva, foreskin) constitutively expressed D-factor RNA. Levels of expression of this gene increased in fibroblasts of each of the tissues after exposure to several stimuli including products of activated macrophages and lymphocytes (tumor necrosis factor (TNF), interleukin 1 and lymphotoxin). Other stimuli were those capable of activating either protein kinase C (12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin), G-binding proteins (NaF) or those inhibiting protein synthesis (cycloheximide). Accumulation of D-factor RNA by TNF may in part be explained by stabilization of D-factor transcripts; TPA and cycloheximide clearly stabilized D-factor transcripts. We and others have shown that these same signals similarly stimulated fibroblasts to express RNAs coding for a variety of cytokines including three colony-stimulating factors as well as interleukins 1 and 6. Taken together, D-factor probably is a participant in the cascade of cytokines that are produced in mesenchymal cells after various stimuli such as bacterial invasion.
Cells, Cultured↗
Mutagenicity of (p-nitrophenyl)adenines in Salmonella typhimurium.
Adenine derivatives having a p-nitrophenyl group at position 2, 8, or 9 were directly mutagenic towards Salmonella typhimurium strains TA98 and TA100, whereas N6-(p-nitrophenyl)adenine was not mutagenic. 2,9- And 8,9-bis-(p-nitrophenyl)adenines were also mutagenic, but N6,9-bis-(p-nitrophenyl)adenine was not. The study on 13 (p-nitrophenyl)adenine derivatives for their Salmonella mutagenicity indicates that only those having a p-nitrophenyl ring directly linked to the purine ring are mutagenic, implying the importance of the coplanar character of the nitrophenyl and the purine rings. The nitro group seems essential for the mutagenicity, as shown from the results of assays using nitroarene-sensitive and -insensitive Salmonella strains. The mutagenic potency of this class of compounds is high, comparable to that of 2-nitrofluorene.
Adenine↗
Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats.
We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Two cases of myocarditis appearing during ACTH therapy for infantile spasms].
We experienced two cases of myocarditis occurring during ACTH therapy for infantile spasms. Myocarditis cases occurred during the reduction of ACTH doses, and viral infection was suspected. Steroid replacement therapy was effective in the both cases. It is important to consider that ACTH therapy for infantile spasms could sometimes lead to severe myocarditis.
Adrenocorticotropic Hormone↗
Selective and effective cleavage of RNAs by vinyladenine-vinylamine copolymer.
Poly(uridylic acid) (poly[U]) and poly(adenylic acid) (poly[A]) are efficiently cleaved, via phosphodiester linkage hydrolysis, at pH 8, 50 degrees C by use of poly(vinyladenine-co-vinylamine) as catalyst. The catalytic activity of the copolymer surpasses the value of poly(vinylamine), indicating a significant role of the adenine residue in the copolymer for the effective catalysis.
Hydrolysis↗
Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myo-inositol supplementation.
To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p less than 0.05) and 64.6% (p less than 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p less than 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldehyde Reductase↗
Flow-regulated continuous positive airway pressure to minimize imposed work of breathing.
We have developed a new continuous positive airway pressure (CPAP) system, which consists of an electropneumatic regulator, a microcomputer, and a pneumotachograph placed between the endotracheal tube and the breathing circuit of the CPAP apparatus. This flow-regulated CPAP (FR-CPAP) system delivers a basal flow and also regulates this flow every 20 msec to match the patient's flow demand. To evaluate the performance of this FR-CPAP system, we compared the imposed work of breathing of the FR-CPAP and continuous flow CPAP (CF-CPAP) systems. A model lung was used to simulate spontaneous breathing. The imposed work of breathing of the FR-CPAP system was less than that of the CF-CPAP system. These results indicate that the FR-CPAP system could minimize the imposed work of breathing of a patient receiving CPAP.
Models, Structural↗
Role of lymphotoxin in expression of interleukin 6 in human fibroblasts. Stimulation and regulation.
IL-6 is a cytokine with a number of biological functions, including stimulation of immunoglobulin synthesis and proliferation of early hematopoietic stem cells. We showed that lymphotoxin stimulated accumulation of IL-6 mRNA in human fibroblasts (W138) in a dose-responsive fashion; tumor necrosis factor-alpha (TNF-alpha) was about threefold more potent than lymphotoxin. Further experiments suggested that stimulation by lymphotoxin was independent of protein kinase C activity, did not require new protein synthesis, and was at least in part a result of increased stabilization of IL-6 mRNA. t1/2 of the IL-6 transcripts increased from 0.3 h in unstimulated cells to 0.85 h in cells stimulated with lymphotoxin. In addition, stimulators of protein kinase C, including phorbol esters and teleocidin, enhanced accumulation of IL-6 mRNA. Cycloheximide (CHX), inhibitor of protein synthesis, also markedly increased levels of IL-6 mRNA. Both CHX and activators of protein kinase C increased by greater than 16-fold the stability of IL-6 mRNA. Further, dose-response studies showed that sodium fluoride (NaF), activator of G-binding proteins, and ouabain, inhibitor of Na+/H+ pump, increased levels of IL-6 mRNA. NaF stimulated IL-6 mRNA levels independent of protein kinase C activity. These results suggest that stimulators of several pathways of signal transduction increase levels of IL-6 mRNA and posttranscriptional stabilization is, in part, the mechanism that many of these signals, including lymphotoxin, use to increase levels of IL-6 RNA.
Cell Line↗
Study on the interaction of aromatic dyes with nucleic acids by means of UV, CD and NMR spectroscopies.
The interaction of several aromatic cationic dyes such as, ethidium bromide (EB), methylene blue (MB), acridine orange (AO), and Hoechst 33258 with calf-thymus DNA and poly(A)-poly(U) duplex was investigated. The different induced extrinsic Cotton effects (greater than 300 nm) were observed for DNA- and RNA-dye complexes. The binding properties of these complexes were examined by UV, CD, and NMR spectroscopies.
Acridine Orange↗
Control of hematopoietic growth factors.
Explore the source record for details and available documents.
Colony-Stimulating Factors↗
Lymphotoxin: stimulation and regulation of colony-stimulating factors in fibroblasts.
Colony-stimulating factors (CSFs) are pivotal for proliferation and function of hematopoietic cells. We found that lymphotoxin, a product of activated lymphocytes, stimulates accumulation of granulocyte-macrophage (GM)-CSF and macrophage (M)-CSF proteins and mRNAs in fibroblasts. An increase in GM- and M-CSF mRNA levels occurred within 2 hours after addition of 1,000 U/mL lymphotoxin and levels plateaued over the next 24 hours. Tumor necrosis factor alpha (TNF alpha) was about five times more potent than lymphotoxin at low concentrations, and was nearly 1.5 to to 2 times more potent at maximally stimulating concentrations of the cytokines. Stimulation by lymphotoxin did not require either new protein synthesis or protein kinase-C stimulation. Stability studies of GM- and M-CSF transcripts in fibroblasts showed that M-CSF mRNA was five times more stable (half-life [t 1/2], 100 minutes) than GM-CSF mRNA (t 1/2, 20 minutes). Stability of these mRNAs was unchanged after stimulation of the cells with lymphotoxin. In addition, exposure of cells to 12-O-tetradecanoylphorbol 13-acetate did not alter stability of M-CSF mRNA but markedly prolonged the stability of GM-CSF mRNA. This is consistent with data showing that the AT-rich consensus region in the 3' untranslated region of many transiently expressed cytokines including GM-CSF but not M-CSF, play a major role in their mRNA stability. Our results suggest that activated lymphocytes can affect hematopoietic cell function and growth by stimulating production of CSFs by mesenchymal cells.
Blotting, Northern↗
Treatment of multiple myeloma with carboquone-prednisolone.
18 previously untreated patients with multiple myeloma were entered in a clinical study of a combination chemotherapy, carboquone (CQ) and prednisolone (P) (CQ-P). Response was observed in 44% of patients treated with CQ-P judged by the criteria for response to chemotherapy. The median survival time was 33 months. Serious toxic reactions seldom occurred. The results suggest that the combination of CQ-P has efficacy in the treatment of multiple myeloma and could have a role among primary chemotherapeutic regimens for the disease. Further clinical trials should be conducted to establish a new drug combination in which CQ is included.
Aged↗
Effects of brief exposure to insulin-induced hypoglycemic serum during organogenesis in rat embryo culture.
We have previously shown that long-term exposure to medium containing insulin-induced hypoglycemic serum during the early phase of organogenesis can adversely affect embryonic development in rat embryo culture and that these effects were mediated through the interruption of glycolytic flux that constituted the principal pathway at this embryonic stage. Further experiments were performed to examine whether brief exposure to the hypoglycemic medium during critical developmental periods would have adverse effects on embryogenesis during embryo culture not only in normal but also in high glucose concentrations. Rat embryos in the early head-fold stage (9.5 days gestation) were grown in vitro for 48 h until neural tube closure occurred; dysmorphogenic lesions were not elicited in either the basal culture medium containing 6.6 mM glucose (control medium) or the hyperglycemic medium supplemented with glucose at a concentration of 33.3 mM. Hypoglycemic mediums (2.2-2.5 mM glucose) were prepared from the serum of rats given insulin intraperitoneally. Postimplantation embryos (in early neural tube formation) were briefly exposed (1 h) to hypoglycemic medium on day 10.3 of gestation during the basal culture. After exposure to the hypoglycemic medium for 1 h during culture in the control medium, embryos showed minor growth retardation and dysmorphogenic lesions (7.1% open neural pores). Exposure to the hypoglycemic medium for 1 h during culture in hyperglycemic medium suplemented with a subteratogenic concentration of glucose (33.3 mM) resulted in greater growth retardation and increased occurrence of dysmorphogenic lesions (17.3% open neural pores).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗