Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 235 records · Page 13Linked to original sources

PubMed1993

Immunologic significance of increased soluble CD8/CD4 molecules in patients with active systemic lupus erythematosus.

This study attempted to estimate soluble CD4(sCD4)/CD8(sCD8) molecules in active systemic lupus erythematosus (SLE) patients. Measurements were made by solid-phase enzyme-linked immunosorbent assay. sCD8 or sCD4 molecules were significantly increased in the patients as compared to control subjects. sCD8 correlated with the erythrocyte sedimentation rate. sCD4 correlated with the anti DNA antibody titer, the IgG concentration, and negatively with the complement titer. An association of these molecules with immunologic abnormalities and disease activity exists in SLE patients.

CD4 Antigens↗

PubMed1993

Long-lasting potentiation of synaptic transmission in the Schaffer collateral-commissural pathway of the guinea pig hippocampus by activation of postsynaptic N-methyl-D-aspartate receptor.

The effects of short-period (2 min) perfusion of conditioning solution, which contains N-methyl-D-aspartate (NMDA), glycine, and spermine, on the synaptic transmission in the Schaffer collateral-commissural pathway were examined in hippocampal slices with the intracellular recording technique. Long-lasting potentiation of excitatory postsynaptic potentials (EPSPs) was induced (as long as the records lasted, up to 3 h in the longest observation) after membrane potentials of postsynaptic neurons were depolarized by current injection during perfusion of the conditioning solution. D-2-amino-5-phosphonovaleric acid (D-AP5), a specific antagonist of NMDA receptors, block the induction of the long-lasting potentiation by perfusion of NMDA containing solution. This potentiation was accompanied by a decrease in the relative magnitude of EPSP amplitude fluctuation (coefficient of variation, CV). The reciprocals of squared CVs (= mean2/variance) were almost proportional to the magnitude of the potentiation, and the ratios of 1/CV2 and the magnitudes of potentiation were not different from those of long-term potentiation (LTP) induced by tetanic stimulation. These findings suggest that long-lasting potentiation is induced solely by activation of postsynaptic NMDA receptors, and transmitter release from presynaptic terminals may be modified by the activation of postsynaptic receptors.

2-Amino-5-phosphonovalerate↗

PubMed1993

Structural study of the sugar chains of porcine factor VIII--tissue- and species-specific glycosylation of factor VIII.

The asparagine-linked sugar chains of blood coagulation factor VIII purified from porcine plasma were released as oligosaccharides by hydrazinolysis. These sugar chains were converted to radioactive oligosaccharides by reduction with sodium borotritide and separated into neutral and acidic fractions by paper electrophoresis. Most of the acidic oligosaccharides were converted to neutral ones by sialidase digestion, indicating that they are sialyl derivatives. The neutral and the sialidase-treated acidic oligosaccharides were fractionated by serial chromatography on immobilized lectin columns. Structural study of each oligosaccharide by sequential exoglycosidase digestion and by methylation analysis revealed that porcine factor VIII contains high mannose-type and bi-, tri-, and tetraantennary complex-type sugar chains. Sixty-seven percent of the complex-type sugar chains contained the Gal alpha 1-->3Gal group, and 23% of the biantennary complex-type sugar chains contained the bisecting N-acetylglucosamine residue. These structures were not detected in the sugar chains of human plasma factor VIII. An in vitro competition study of von Willebrand factor and anti-Gal antibody for binding to factor VIII revealed that von Willebrand factor prevented antibody binding to Gal alpha 1-->3Gal groups in porcine factor VIII sugar chains. This suggests that anti-Gal antibody present in human plasma may not interact with the sugar chains of therapeutic porcine factor VIII. Reverse-transcription polymerase chain reaction was used to identify porcine tissues producing FVIII mRNA. These studies revealed that the kidney is one of the major tissues expressing factor VIII which may contain the sugar chains with the bisecting N-acetylglucosamine residue.

Animals↗

PubMed1993

Increased soluble IL-2 receptor in serum of patients with systemic lupus erythematosus.

We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

Adolescent↗

PubMed1993

Suppression of gamma- and neutron-induced neoplastic transformation by ascorbic acid in Balb/c 3T3 cells.

The effects of ascorbic acid on the neoplastic transformation induced by 60Co gamma-rays or 252Cf fission neutrons were studied. The transformation induced by each of the radiations was markedly suppressed when ascorbic acid was added daily to the culture medium during the first 8 days of the post-irradiation period. If ascorbic acid was added for a total of 8 days as mentioned above, but with 1 day interruption in the middle, the suppression of transformation was decreased. Ascorbic acid also suppressed the promotion of radiation transformation by 12-O-tetradecanoylphorbol-13-acetate (TPA) when both chemicals were added to the medium together. However, promotion of radiation transformation by TPA was observed if both the chemicals were added sequentially during the post-irradiation period, i.e. ascorbic acid for the first 7 days followed by TPA. These results suggest that continuous administration of ascorbic acid for a certain number of days is needed to suppress the radiation transformation, and also suggest that it acts on the promotion stage of transformation.

3T3 Cells↗

PubMed1993

Dose-rate effects of neutrons and gamma-rays on the induction of mutation and oncogenic transformation in plateau-phase mouse m5S cells.

The dose-rate effect of 252-californium neutrons was investigated using confluent cultures of mouse m5S cells. The relative biological effectiveness (RBE) of neutrons for oncogenic transformation was increased from 3.3 to 5.1 when the dose-rate was reduced from 1.8 to 0.12 cGy/min. Similarly, neutron RBE values for HPRT- mutation were 4.9 and 7.4 at dose-rates of 1.8 and 0.12 cGy/min, respectively. The increases in RBE as dose-rate was reduced were due mainly to diminished transformation- and mutation-induction by gamma-rays (the standard radiation). The yields of neutron-induced oncogenic transformation as well as neutron-induced mutation were constant for both dose rates. Our observation contrasts with reports by others using proliferating cells where both oncogenic transformation and mutation were enhanced with neutron exposure at a reduced dose-rate, the so-called inverse dose-rate effect. Since m5S cells are sensitive to postconfluent inhibition of cell division, this observation could be ascribed to cell growth conditions used in these experiments. The mechanism of the inverse dose-rate effect of neutrons suggests that the enhancement of neutron-induced mutation and oncogenic transformation at a reduced dose-rate is strongly associated with cell proliferation during exposure.

Animals↗

PubMed1993

Cell cycle dependence for the induction of 6-thioguanine-resistant mutations: G2/M stage is distinctively sensitive to 252Cf neutrons but not to 60Co gamma-rays.

Cell cycle dependence for the induction of 6-thioguanine-resistant mutation was investigated using synchronized mouse L5178Y cells after exposure to 4 Gy to 60Co gamma-rays or 1 Gy of 252Cf radiation (fission neutrons). Maximal mutation frequency was observed immediately after release from colcemid block (G2/M phase) after 252Cf radiation, whereas it was 1 h after the release (G1 phase) after 60Co gamma-rays. When the mutation frequency was plotted against the surviving fraction, a general correlation was observed between the two parameters except for G2/M and G1 phases which were more mutable per lethal event for 252Cf and 60Co radiations, respectively.

Animals↗

PubMed1993

Radiation-induced apoptosis and necrosis in Molt-4 cells: a study of dose-effect relationships and their modification.

Cell death induced by various radiation doses in Molt-4 and L5178Y cells was studied. Molt-4 cells have a low threshold for induction of interphase death while L5178Y cells have a high threshold. Interphase death in Molt-4 cells at doses > 100 Gy and in L5178Y cells at doses > 300 Gy showed typical necrosis. In contrast, cell death in Molt-4 cells after 2-30 Gy had features of both apoptosis and necrosis; the appearance of orcein-stained cells in the light microscope was suggestive of apoptosis, showing chromatin margination and apoptotic bodies. The concomitant appearance of non-viable cells as estimated by either orcein staining or eosin dye staining correlated well with this. Early cell swelling and a diffuse smear pattern in DNA gel electrophoresis were however suggestive of necrosis. Detailed electron microscopic observations revealed that events leading to the interphase death of Molt-4 cells after 2-30 Gy involved complicated pathways which included both apoptotic changes in the nucleus and necrotic changes in the cytoplasm. TPA not only had a protective effect on the interphase death of Molt-4 cells, but also converted the mode of cell death from interphase death to mitotic death after low doses of radiation. Cycloheximide and H-7, known to inhibit apoptosis in irradiated thymocytes, had no protective effect on the interphase death of Molt-4 cells, suggesting that the events leading to interphase death in Molt-4 cells might be different from those in thymocytes. BrdUrd-labelling had a sensitizing effect on the radiation response, but no effect on interphase death in Molt-4 cells thus suggesting that DNA damage may not be responsible for interphase death.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Fluorescent molecular rotor binding to actin.

1-(2-Hydroxyethyl)-6-[(2,2-dicyano)vinyl]-2,3,4-trihydroquinoli ne (DCQ) is a fluorescent dye and its fluorescence yield is determined by a freedom of intramolecular rotation. When DCQ was added to an actin solution, its fluorescence intensity increased as the actin molecule transformed from G-actin to F-actin. This fluorescence intensity increase was induced both by the higher binding constant of the dye to F-actin than to G-actin and by the higher fluorescence yield of the dye bound to F-actin than to G-actin. DCQ bound more strongly to Mg(2+)-F-actin than to Ca(2+)-F-actin, resulting in higher fluorescence intensity of DCQ-Mg(2+)-F-actin solution than of DCQ-Ca(2+)-F-actin solution. DCQ did not distinguish Mg(2+)-G-actin and Ca(2+)-G-actin. Thus, DCQ is a good probe for polymerization of actin and polymorphism of F-actin.

Actins↗

PubMed1993

A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines.

A T-lymphocyte-specific enhancer located 13 kb upstream of the murine CD4 gene was recently shown to be required for the developmentally regulated expression of CD4. We have previously identified three nuclear protein binding sites in this enhancer; one of these sites, CD4-3, is essential for expression and contains two E-box core motifs (CANNTG) adjacent to each other in the sequence TAACAGGTGTCAGCTGGT. In electrophoretic mobility shift assays using the CD4-3 oligonucleotide as a probe, three nuclear protein complexes, termed CD4-3A, -B, and -C, were detected with nuclear extracts from T-cell lines. CD4-3A, which involves nuclear protein binding to the 5' E-box, was detected only with nuclear extracts from lymphoid cells. Specific antisera were used to show that the CD4-3A complex contains a heterodimer or heterooligomer of basic helix-loop-helix transcriptional factors, E12 or a related factor and HEB, which is expressed predominantly in thymus. Consistent with this finding, in vitro-translated E12 and HEB proteins, as homodimers or heterodimers, bound preferentially to the 5' E-box. Point mutations in the 5' E-box, but not in the 3' E-box, abolished CD4 enhancer activity. Furthermore, overexpression of Id, a protein that forms inactive heterodimers with E12/E47, blocked CD4 enhancer activity in T cells. These results suggest that a heterodimer composed of HEB and E12 or a closely related protein plays a critical role in CD4 enhancer function by interacting with the 5' E-box motif of the CD4-3 site in vivo.

Amino Acid Sequence↗

PubMed1993

Malignant tracheobronchial obstructive lesions: treatment with Gianturco expandable metallic stents.

Gianturco expandable metallic stents were placed in 14 patients with 19 malignant lesions who had tracheobronchial stenosis and/or obstruction together with dyspnea. In all 14 patients, stenotic and/or obstructive changes disappeared immediately after the procedure, and the dyspnea improved. Lumina at the sites of tracheal lesions expanded from a mean of 3.9 mm in diameter before stent placement to a mean of 13.9 mm after stent placement. Lumina at the sites of bronchial lesions expanded from a mean of 2.1 mm to a mean of 10.3 mm. Lumina at the sites of lesions caused by extrinsic compression expanded to a mean of 89.7% of normal, while lumina at the sites of lesions caused by intraluminal tumor growth expanded to a mean of 63.2% of normal. There was improvement of at least one grade of the Hugh-Jones classification in 12 patients. Ten of the patients died; in two of these patients, restenosis developed.

Adult↗

PubMed1993

Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction.

BACKGROUND: Dysfunction after thrombolytic therapy of acute myocardial infarction (MI) may be reversible. Early after myocardial infarction, both reversible and irreversible injury may be manifested by regional wall motion abnormalities. Improved wall thickening during dobutamine infusion (dobutamine-responsive wall motion) may accurately identify reversibly injured segments. METHODS AND RESULTS: To determine whether dobutamine-responsive wall motion accurately detects reversible postischemic dysfunction irrespective of infarct location, multistage (baseline, 4 and 12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography (DE) was performed within 7 days of thrombolytic therapy. Resting echocardiography was repeated > or = 4 weeks after MI, and reversible dysfunction was defined as improved wall motion. The accuracy of dobutamine-responsive wall motion was compared with that of signs of early reperfusion, non-Q-wave MI, and peak creatine kinase (CK). Sixty-three patients underwent DE without complications. Follow-up echocardiograms were done in 51 (81%) of these patients, and wall motion improved in 22 (41%). Dobutamine-responsive wall motion during all stages of DE was very specific for reversible dysfunction (90% to 93%) but sensitive (86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1). Non-Q-wave MI and a low peak CK (< 1000 IU/mL) were also specific (89% to 93%) but less sensitive (64% [P = .16] and 55% [P < .05], respectively). Signs of early reperfusion did not identify postischemic dysfunction. Low-dose dobutamine-responsive wall motion and non-Q-wave MI independently identified reversible dysfunction, but only dobutamine-responsive wall motion was sensitive in all infarct locations. Non-Q-wave MI was sensitive only in anterior infarction. CONCLUSIONS: Multistage dobutamine echocardiography can be performed safely early after thrombolytic therapy. Low-dose dobutamine-responsive wall motion accurately detected reversible dysfunction in all infarct locations. Dobutamine-responsive wall motion and non-Q-wave infarction may be very useful for accurately identifying reversible dysfunction early after thrombolytic therapy for acute MI.

Adult↗

PubMed1993

Chemical modification of an antitumor alkaloid, 20(S)-camptothecin: E-lactone ring-modified water-soluble derivatives of 7-ethylcamptothecin.

7-Ethylcamptothecin (1d), a model which does not have any site on the A-ring for further modification was converted into water-soluble derivatives by opening the E-ring lactone. 1d was heated in N,N-dimethylenediamine to yield amide 2a, and this was then acylated to furnish 3a-q, which were soluble in water as their HCl salts. The propionyl (3b), butyryl (3c) and methylthiopropionyl (3h) derivatives showed higher activity than the sodium salt of 1d. The acyl group makes the derivatives more lipophilic, and ease of hydrolysis of amide 2a to 1d is thought to be necessary for significant activity.

Animals↗

PubMed1993

Chemical modification of antitumor alkaloids, 20(S)-camptothecin and 7-ethylcamptothecin: reaction of the E-lactone ring portion with hydrazine hydrate.

The structure of the N-amino pyridone (4a) obtained by the reaction of camptothecin (1a) with hydrazine was determined by X-ray crystallography. A mixture of 7-ethylcamptothecin (1b) and hydrazine hydrate was stirred at room temperature, and the hydrazide (2b) was isolated as its diacetate 2c. Treatment of the 17-O-acetyl amide (5a) with hydrazine gave 1b (74% yield) and the N-amino lactam 6 (11% yield). Compounds with bulky acyl groups, 5c--e, gave 6 in modest yields. The N-amino lactam 6 was smoothly dehydrated into the pyridone 4d by refluxing in hydrazine hydrate.

Animals↗

PubMed1993

Effects of dose rate and energy level on fission neutron (252Cf) tumorigenesis in B6C3F1 mice.

The effects of the dose rate and the energy of fission neutrons using an iron block on tumorigenesis in B6C3F1 mice were examined. Six-week-old female animals were divided into 4 groups and exposes to 252Cf neutron irradiation at dose rates of 0.05 cGy/min, with (Group 1) or without (Group 2) filtering through a 10 cm thick iron block, 0.8 cGy/min (Group 3) or 0 (Group 4 controls). Total neutron exposure was 50 cGy in each of groups 1-3 and total irradiation dose was 56, 75 and 75 cGy in Groups 1-3, respectively. Total tumor incidences or multiplicity were significantly higher in Group 3 than in Group 1. A similar tendency was observed as compared to Group 2, ovarian and Harderian gland tumors being mainly affected and adrenal tumors were significantly higher in Group 2 than in Group 1. The results indicated a clear increase in tumorigenesis with the higher dose rate and no filtering influence of iron was evident, despite the drop in neutron energy level.

Animals↗

PubMed1993

Irreversible suppression of CD8 expression in CD4-CD8+ thymocytes upon in vitro stimulation.

CD8 (Ly-2) expression was suppressed in purified murine CD4-CD8+ thymocytes at the mRNA level upon continuous stimulation with PMA and ionomycin in the presence of rIL-2. The level of CD8 expression on CD4-CD8+ thymocytes was reduced gradually during the culture and a majority of them turned into CD4-CD8- cells after 48 hr. This suppression was not transient, since CD8 expression was not recovered on these cells in additional 48 hr of culture without PMA and ionomycin. The suppression was dependent on the concentrations of PMA and ionomycin, and inhibited by adding an immunosuppressant, CsA to the culture. Treatment with either PMA or ionomycin alone did not induce suppression of CD8. Crosslinking of CD3-epsilon chains also induced suppression of CD8 for a part of CD4-CD8+ thymocytes. Interestingly, CD8 expression was hardly suppressed in CD4-CD8+ peripheral T lymphocytes, suggesting that the mechanisms of suppression of CD8 is developmentally regulated. We propose that the suppression of CD8 expression at CD4-CD8+ stage involves an additional mechanism of negative selection of thymic T cells.

Animals↗

PubMed1993

[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients.

Adult↗

PubMed1993

[Malignant fibrous histiocytoma of the spermatic cord: a case report].

A case of malignant fibrous histiocytoma of the spermatic cord is reported. A 44-year-old man was admitted because of a painless, gradually enlarging mass in the left scrotum. Local tumor excision and subsequent radical inguinal orchidectomy was performed. The histological diagnosis was malignant fibrous histiocytoma. There were no signs of recurrence or metastasis 8 months after the operation. Malignant fibrous histiocytoma in the spermatic cord is rare. We reviewed 34 previously reported cases. The rate of local recurrence and distant metastasis are 34.5% and 17.2%, respectively.

Adult↗