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Biomedical subjects

T Akizawa

Publications and source records attributed to T Akizawa.

At least 19 recordsLinked to original sources

Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes.

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.

Base Sequence

Isolation of substance P binding protein from rat brain.

Substance P (SP) binding protein of rat brain was solubilized by digitonin. The solubilized proteins were then purified by sequential gel filtration, concanavalin A lectin Sepharose, and SP-affinity chromatography. The calculated molecular weight of this purified SP binding protein was 76-74 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbits were immunized with the purified protein and resulting polyclonal anti-sera were tested. The immune serum significantly inhibited [3H]SP binding to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate solubilized membrane fractions from rat brain, whereas pre-bleed antiserum failed to inhibit the binding. This polyclonal antibody also inhibited the activity of 45Ca influx into astroglioma cells stimulated by SP, but does not inhibit that stimulated by histamine. Furthermore, this polyclonal antibody recognized the 76-74 kDa band as assessed by Western blotting. These data strongly suggest that this polyclonal antibody could recognize a part of the natural SP receptor site.

Animals

Nafamostat as anti-coagulant for membrane plasmapheresis in high bleeding risk patients.

Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients.

Adolescent

Effects of recombinant human erythropoietin and correction of anemia on platelet function in hemodialysis patients.

To clarify the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 hemodialysis patients with renal anemia. Anemia improved significantly 12 weeks after r-HuEPO therapy (stage II) compared to pretreatment (stage I) and 6 weeks discontinuation (stage III) periods. Platelet count did not change among the three stages, however, mean platelet volume increased significantly at stage II in comparison with stage I. Ivy bleeding time (BT) significantly shortened at stage II and prolonged again at stage III. Although there were no significant changes in platelet aggregation, plasma TxB2, 6-keto-PGF1 alpha, F.VIII:C and F.VIII:Ag levels throughout the study, platelet adhesion and von Willebrand factor (vWf):Ag significantly increased at stages II and III. Augmentations in these parameters were more remarkable in BT-shortened patients (n = 12) than in the BT-unchanged group. These results indicate that correction of anemia with r-HuEPO brought about improvement in uremic hemostatic defect via the increase in red cell volume and vWf:Ag, and new production of platelets, reflected by the improvement in platelet adhesion.

Adult

A study of oral adsorbent in chronic renal failure.

In order to examine the effect on the progression of chronic renal failure (CRF), we have applied an oral adsorbent (AST-120) composed of spherical porous carbon particles to patients with chronic renal failure undergoing conservative therapy. Its effect was observed in improvement of uremic symptoms, improvement of slope in linear regression of reciprocal of serum creatinine vs. time plots and delayed initiation of hemodialysis, compared to control patients, together with reduced uremic peak 2a in HPLC analysis of serum and lower levels of beta 2 microglobulin in AST-120 group than in control. The improvements of uremic symptoms, creatinine and 2a levels were confirmed in double blind study where background of patients were evenly randomized between AST-120 and placebo groups and no improvement was observed in placebo group. The result leads us to conclude that the oral adsorbent therapy is expected as an useful therapy for retardation of progression of CRF.

Administration, Oral

[The effects and pharmacokinetics of rhG-CSF on the treatment of neutropenia in patients with renal failure].

rhG-CSF (recombinant human granulocyte colony stimulating factor) promotes production and release of neutrophil from bone marrow, and it enhances neutrophil function. In this study, the pharmacokinetics, effects on neutrophil and immune functions and efficacy and safety of rhG-CSF were studied in patients with end-stage renal failure (CRF). To 9 patients with CRF; 2 patients on conservative therapy and 7 patients under regular hemodialysis, 50 micrograms/m2 rhG-CSF were administered intravenously under the schedule of single or 2 week consecutive injection. In single injection study, serial changes in plasma rhG-CSF concentration and peripheral blood cell count were examined following the administration. In consecutive injection study, plasma rhG-CSF concentration, anti-rhG-CSF antibody, peripheral blood cell counts, blood chemistry and coagulation factors, and neutrophil and immune functions were examined. As the results, 1) Half life of rhG-CSF, 2.87 +/- 0.65 hr, was about 2 times longer than that in healthy subjects, and it was not affected by hemodialysis treatment. 2) Marked increase in leukocyte and neutrophil counts and mild increase in lymphocyte count were observed during single and consecutive administration of rhG-CSF. There was no significant change in other leukocyte differentiations, RBC, or platelet count. 3) Neutrophil alkaline phosphatase score increased significantly during single and consecutive administration, and other neutrophil function also improved in several patients with impaired neutrophil function. 4) Slight bone pain and increase in serum alkaline phosphatase were observed in about a half of patients during consecutive injection study. Neither antibody nor accumulation of rhG-CSF was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[A case report of invasive thymoma presenting as a solitary metastatic lesion of the lung].

A 66-year-old woman visited our hospital for further investigation of a coin-shaped lesion in the right lower lung field. After admission, CT-scan revealed an anterior mediastinal tumor. Thymoma and lung metastasis from thymoma were suspected. At thoracotomy, an invasive thymoma involving the left phrenic nerve, the left upper lobe, and the pericardium was found, and the diagnosis of lung metastasis was made. Postoperative pathological findings showed a predominantly lymphocytic thymoma with round and oval-shaped epithelial cells, and the metastatic lung lesion revealed the same findings. Postoperative radiotherapy (4000 rads) and chemotherapy with a combination of CDDP, VDS, and CPA were administered. The metastasis of thymoma is not rare, but most often it is found after operation. In this case the diagnosis of metastatic thymoma was made pre-operatively from a solitary lung lesion.

Aged

HTLV-1 Rex protein accumulates unspliced RNA in the nucleus as well as in cytoplasm.

The Rex protein of human T-cell leukemia viruses (HTLV) is a trans-acting regulator inducing the expression of gag and env mRNA containing the introns. The rex gene can also induce expression of unspliced RNA of human immunodeficiency viruses (HIV). We have analyzed the level of spliced and unspliced RNAs in nucleus and cytoplasm to understand the mechanism by which the Rex protein modulates RNA processing. With the gag gene of HTLV-1, the unspliced RNA was accumulated by Rex protein in both nucleus and cytoplasm. However, the apparent effects on nuclear unspliced RNA depended on the reporter genes: with the env gene of HTLV-1 as well as that of HIV-1, Rex did not accumulate the unspliced RNA in nucleus, but did so only in cytoplasm. These results clearly indicate that Rex protein not only activates the nuclear export of unspliced RNA, but also modulates some steps of RNA processing before the splicing, probably through stabilization of the precursor RNA.

Cell Nucleus

Cutaneous reactions caused by experimental exposure to jellyfish, Carybdea rastonii.

Dermatitis caused by contact with tentacles of jellyfish was studied on 25 volunteers. Two tentacles cut from a living jellyfish, Carybdea rastonii, were applied on each of the forearms and skin reactions were observed. All volunteers complained of severe pain, which lasted from 10 min to 8 hrs. Erythema and wheal appeared within 3 to 4 min and enlarged for 15 to 20 min. Erythema subsided within 24 hrs to 3 days in all but two individuals. Seven to 13 days after the application, linear erythema and papulo-vesicular lesions with pruritus were observed on the forearms of 15 out of 25 volunteers tested. These flare-up lesions lasted for one week leaving slight pigmentation. Histological findings from the flare-up lesions corresponded to those of allergic contact dermatitis. The lymphocyte response to the jellyfish venom in the subjects who had recurring lesions was greater than that in either the subjects with no recurring lesions or the control group, who was never exposed to jellyfish.

Adult

Clinical application of Fragmin (FR-860) in hemodialysis: multicenter cooperative study in Japan.

A multicenter cooperative study was designed to evaluate the efficacy and safety of Fragmin (FR-860) as an anticoagulant in hemodialysis. Sixty-one stable maintenance hemodialysis patients were enrolled from 14 institutions in Japan. The study period was fixed at 2 weeks. Dosage requirements were 15.0 to 20.0 anti-Xa U/kg as bolus and 7.5 to 10.0 anti-Xa U/kg/hr as continuous infusion. The total dosage of Fragmin was 2505 +/- 127 anti-Xa U compared with 6124 +/- 190 U of conventional heparin. No differences were observed in residual blood in extracorporeal circuits between the groups. The hemostasis times at puncture sites after completion of dialysis were significantly shortened in the Fragmin group (7.9 +/- 0.7 minutes) when compared with the conventional heparin group (11.4 +/- 1.1 minutes; p less than 0.01). Plasma anti-Xa levels were 0.24 +/- 0.03 and 0.36 +/- 0.04 U/ml 1 hour after the initiation and at the completion of dialysis, respectively. ACTs, measured by the Hemochron method, were not prolonged during dialysis. APTTs varied from 34.3 +/- 1.2 before dialysis to 41.0 +/- 1.9 (p less than 0.01) 1 hour after the start of dialysis and 39.9 +/- 1.6 seconds (p less than 0.01) at the end of dialysis. Plasma AT III activity increased from 96.8 +/- 2.5% before dialysis to 113.0 +/- 3.2% (p less than 0.01) at the end of dialysis. No significant changes were observed in both ADP- and collagen-induced platelet aggregation during dialysis. Dialysis efficiency was the same for both groups. Slight itching developed in one of 61 cases. No abnormal laboratory data were observed during the study. The efficacy, safety, and utility rates were 98.4, 98.5, and 98.4%, respectively. Fragmin proved to have a higher utility rate and was a good and convenient alternative to conventional heparin as an anticoagulant in hemodialysis treatment.

Antithrombin III

[Beneficial characteristics of protease inhibitor as an anticoagulant for extracorporeal circulation].

Clinical characteristics of protease inhibitor, nafamostat mesilate (FUT-175:FUT), as an anticoagulant for extracorporeal circulation (ECC) were evaluated in hemodialysis and membrane plasmapheresis. FUT inhibited broad enzymatic systems including coagulation, platelet, complement, fibrinolysis and kinin cascades, which were commonly activated in the course of ECC. FUT showed regional anticoagulability, in which anticoagulating effects were firmly limited in extracorporeal circuit, and hemostatic time after ECC was significantly shortened by the use of FUT. FUT had no effects on lipid and bone metabolisms and FUT could not be adsorbed to anion exchange resin. These results indicate that FUT possesses superior characteristics as an anticoagulant for ECC to heparin, and FUT is very useful especially for ECC of patients with high bleeding risk.

Anticoagulants

[The effects of r-HuEPO on platelet function and coagulation factors in hemodialysis patients].

To evaluate the effects of correction of anemia with recombinant human erythropoietin (r-HuEPO) on the hemostatic defects in uremia, hemostatic parameters were examined in 18 patients with renal anemia receiving hemodialysis (HD). During the study, hematocrit (Ht) increased from 22.9 +/- 3.1% (mean +/- SD) at pre-treatment (stage-I) to 31.0 +/- 3.0% 12 weeks after 3000 IU intravenous r-HuEPO administration at the end of every HD (stage-II), and decreased to 26.2 +/- 4.2% 6 weeks after r-HuEPO discontinuation (stage III). Platelet count did not change among these three stages, however, mean platelet volume significantly increased at stage II compared to stage I. Ivy bleeding time (Ivy-BT) significantly shortened at stage II (I; 14.3 +/- 6.0, II; 10.1 +/- 6.5 min, p less than 0.01), and prolonged again at stage III (p less than 0.05 vs stage II). Among the patients, 6 out of 18 patients did not show any reduction in Ivy-BT (unchanged group). Though there were no significant changes in platelet aggregation rates, plasma TxB2, 6-keto-PGF1 alpha, F. VIII: C, and F. VIII: Ag levels throughout the study, platelet adhesion rate was significantly improved at stage II (I; 11.8 +/- 6.8, II; 19.6 +/- 12.8%, p less than 0.05), and similar augmentation in vWf: Ag was observed. Improvement in these two parameters were more remarkable in shortened Ivy-BT group (n = 12) than in unchanged group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult