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Biomedical subjects

T Akizawa

Publications and source records attributed to T Akizawa.

At least 91 records · Page 5Linked to original sources

Nafamostat mesilate: a regional anticoagulant for hemodialysis in patients at high risk for bleeding.

107 hemodialysis patients at high risk for intradialytic bleeding due to previous surgery or active bleeding from other sites were treated with nafamostat mesilate (FUT-175; FUT) as hemodialysis anticoagulant for 2 weeks. In contrast to heparin. FUT prolonged clotting times only in the extracorporeal circuit. Clotting times were not prolonged even at the conclusion of the treatment, and bleeding from the puncture site after removal of the needle was shorter than with heparin. The exacerbation of bleeding by hemodialysis was noted in only 21 out of 573 hemodialysis procedures (3.7%), and 134 of 145 hemodialysis procedures (92.4%) with active bleeding were successfully completed without increasing the bleeding. Adverse effects of FUT were noted in only 6 cases (5.6%) or 1.2% of HD procedures. These results indicate that FUT is a very useful anticoagulant for HD, especially in patients with high risk of bleeding.

Aged↗

Role of uremic and endothelial factors in the development of beta 2-microglobulin amyloidosis.

To clarify the importance of uremic and endothelial factors in the development of beta 2-microglobulin (beta 2m) amyloidosis, in vitro evaluations were carried out using cultured synoviocytes and synovial tissues. Synoviocytes of patients with chronic renal failure were cultured with media containing uremic or normal serum. In cultures with uremic serum, greater proliferation of synoviocytes and stronger expression of CD68, beta 2m, interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) on synoviocytes were observed, compared with those containing normal serum. Uremic serum stimulated greater production of IL-1 beta and TNF alpha than normal serum (P < 0.05 for IL-1 beta, P < 0.01 for TNF alpha). Addition of supernatant of endothelial cell culture to medium containing uremic serum significantly accelerated production. After a three month culture of uremic synovial tissue, embedded in 3% type 1 collagen gel with uremic serum, beta 2m-positive 10 nm fibrils were recognized around the synoviocytes. In culture with uremic serum plus supernatant of endothelial cell culture, positive Congo red staining was noted. These findings indicate that uremic serum plays a significant role in the development of synovial beta 2m amyloidosis and that endothelial cell-derived factors contribute to the formation of beta 2m amyloid.

Amyloidosis↗

Bcl-3, a member of the I kappa B proteins, has distinct specificity towards the Rel family of proteins.

Expression of the bcl-3 gene is demonstrated to be elevated in some B-cell chronic lymphocytic leukemias with a chromosomal translocation, t(14;19)(q32;q13.1). Bcl-3 protein has seven tandem ankyrin repeats that are also found in I kappa B proteins, inhibitors of Rel/NF kappa B transcription factors. In this paper, we demonstrate that Bcl-3 is a member of I kappa B family of proteins with a novel specificity. Bcl-3 preferentially associates with the p50 of NF kappa B, and the nuclear localization signal of p50 is required for this association. Bcl-3 inhibits the DNA-binding activity of p50 homodimers but not that of p50-p65 heterodimers. Transient transfection experiments revealed that appropriate expression of Bcl-3 results in inhibition of the function of p50 homodimers but not that of p50-p65 heterodimers, whereas pp40 and I kappa B gamma inhibit the function of both p50 homodimers and p50-p65 heterodimers. These studies suggest that Bcl-3 could modulate the transcription in a way different from pp40 and I kappa B gamma.

B-Cell Lymphoma 3 Protein↗

[A case of pulmonary arteriovenous fistulas (PAVF) treated with detachable balloon embolotherapy].

A case of pulmonary arteriovenous fistulas (PAVF) treated with detachable balloon embolotherapy is reported. A 31-year-old man was admitted to hospital because of polycythemia and hypoxemia. He had a history of dyspnea on exertion and transient cerebral ischemic attacks (TIA). Chest roentgenogram revealed a peripheral lobulated lesion in the right upper lung field and a coin lesion in the left lung field connected by dilated blood vessels to each hilus. Pulmonary angiography and right heart catheterization was performed. Four PAVFs were observed in bilateral lung field, and the intrapulmonary shunt ratio was 25.8%. Because the patient was symptomatic, we embolized each PAVF with a detachable balloon without complications. After embolotherapy, there was improvement in his symptoms. hypoxemia and shunt ratio. Recent reviews have highlighted the need to consider embolotherapy for bilateral multiple PAVF. We conclude that embolotherapy with detachable balloon is a very useful procedure for treatment of bilateral multiple PAVF.

Adult↗

[Clinical study of tuberculous pleuritis, diagnosed by thoracoscopy using flexible fiberoptic bronchoscope].

Examination by thoracoscopy, using flexible fiberoptic bronchoscope, was performed in 43 patients with pleural effusion according to our reported method. In these patients, 14 cases were diagnosed as tuberculous pleuritis. These 14 cases were investigated with respect to clinical and thoracoscopic findings. Their mean age was 38.1 years, and 11 cases were younger than 50 years old (78.5%). The male:female ratio was 2/1. Clinical symptoms recognised were fever (100%), cough (64.2%), chest oppression (50%) and sputum (35.7%). In 5 cases, gastrointestinal symptoms were recognized such as vomiting, abdominal pain, and diarrhea. Tuberculin reaction was positive in all patients with tuberculous pleuritis on admission. With respect to the thoracoscopic findings of tuberculous pleuritis, yellow-white miliary granulomas were observed on the parietal pleura in 12 cases (85.7%), and this characteristic finding was especially observed at the apex. Biopsy specimens, obtained from these miliary granulomas on the parietal pleura showed histological findings of tubercles. In the other 2 cases, generalized reddening of the entire parietal pleura was observed, with no yellow-white miliary granulomas. Biopsy specimens obtained from the reddened lesions on the parietal pleura showed histological findings of tubercles, and these 2 cases were also diagnosed as tuberculous pleuritis. These results indicate that this method may be very useful for the diagnosis of tuberculous pleuritis in patients with pleural effusion.

Adolescent↗

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↗