Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 235 records · Page 13Linked to original sources

PubMed1995

beta-Endorphin enhances phagocytosis of latex particles in mouse peritoneal macrophages.

The effects of beta-endorphin (beta End) on phagocytosis in peritoneal macrophages were examined by using flow cytometry (FCM). Beta End enhanced phagocytosis in a dose-dependent manner. Leucine-enkephalin (Leu-Enk), methionine-enkephalin (Met-Enk), alpha-endorphin (alpha End), gamma-endorphin (gamma End), alpha End (18-31) and beta End (28-31) had no such activity. Beta End (1-27) and beta End (6-31) enhanced phagocytosis less effectively than beta End did. Naloxone did not inhibit the enhancement of phagocytosis induced by beta End. Unstimulated control phagocytosis was partially suppressed in Ca2(+)-free EGTA-containing solution and even in this solution beta End enhanced phagocytosis. However, the enhancement was suppressed in the solution containing BAPTA-AM. The present study showed that beta End enhanced extracellular Ca2+ ([Ca2+]o)-dependent and -independent phagocytosis and that the enhancement is largely dependent on intracellular Ca2+ ([Ca2+]i). These results support the contention that beta End is one of the mediators that modulates the immune system.

Amino Acid Sequence↗

PubMed1995

Gel chromatographic analysis of cyclosporin and its metabolites in human blood compartments.

Gel chromatography combined with specific and non-specific cyclosporin radioimmunoassays was adopted for quantitative analysis of cyclosporin and metabolites in free and protein-bound forms in blood compartments of kidney transplant patients. The analytical method was proved to be useful for the purpose, although plasma protein-bound forms of neither cyclosporin nor metabolites could be quantitated in the system. The present study also provided, by gel chromatographic analysis, additional examples to prove that concentrations of cyclosporin metabolites in blood compartments may not be deduced or inferred simply from those of cyclosporin.

Administration, Oral↗

PubMed1995

Generation of free radicals and messenger function.

Free radicals are toxic agents that are produced as by-products of metabolic activity. A number of antioxidant mechanisms work to protect cells from damage. Recent evidence indicates, however, that free radicals and related oxidants such as hydrogen peroxide may also have a beneficial role, working as messengers to control cell function. These agents are generated in response to agonists, production is regulated by intracellular signal pathways, and they appear to be used to control particular cellular processes. Free radicals may perform these functions in a number of cell types. Also, they are produced in muscles and there is evidence that they may work as messengers in smooth muscle cells.

Animals↗

PubMed1995

Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene.

To investigate the clonality of uterine leiomyomas, we developed a PCR-based method involving the differential inactivation of the X-chromosome-linked phosphoglycerokinase (PGK) gene. Small DNA samples of 22 leiomyomas from 9 Japanese patients, showing heterozygosity at the BstXI site of the PGK gene, were digested with the methylation-sensitive restriction enzyme HpaII. Only the inactive (methylated) PGK gene allele was selectively amplified by PCR followed by digestion with BstXI and electrophoresis. All leiomyoma samples consisted of a single type of inactive allele, even though alleles were detected that were specific to each nodule. The results indicated that all leiomyoma nodules were unicellular in origin but independently generated in the uterus.

Adult↗

PubMed1995

Specificity of prohormone convertase endoproteolysis of progastrin in AtT-20 cells.

Biologically active peptide hormones are synthesized from larger precursor proteins by a variety of posttranslational processing reactions. Endoproteolytic cleavage at the Lys74-Lys75 dibasic processing site of progastrin is the major determinant for the relative distribution of gastrin heptadecapeptide and tetratriacontapeptide in tissues. Thus, we explored the ability of two prohormone convertases, PC1/PC3 and PC2, to cleave this important site within progastrin. We expressed wild-type human gastrin cDNA and mutant cDNAs in which the Lys74Lys75 site was changed to Lys74Arg75, Arg74Arg75, and Arg74Lys75 residues in AtT-20 cells. Because AtT-20 cells express Pc1/PC3 but not PC2, we also coexpressed a cDNA encoding PC2 in both wild-type and mutant gastrin-producing AtT-20 cells. Wild-type Lys74Lys75 and mutant Arg74Arg75 progastrin processing sites were efficiently cleaved in AtT-20 cells only after coexpression of PC2. Mutant Lys74Arg75 progastrin was readily processed in cells in the presence or absence of PC2 coexpression, but, in contrast, mutant Arg74Lys75 progastrin was inefficiently cleaved regardless of PC2 coexpression. Northern analysis revealed the presence of PC2 but not PC1/ PC3 in canine antral gastrin-producing G cells. These data suggest that PC2 but not PC1/PC3 is responsible for the cleavage of the Lys74Lys75 site in wild-type progastrin.

Amino Acid Sequence↗

PubMed1995

Effects of inhibitors of ouabain-sensitive Na+, K(+)-ATPase and Li+ ions on the neuromuscular transmission of the frog.

The effect of blockade of ouabain-sensitive alpha 2 and alpha 3 (neural type) isozymes of Na+, K(+)-ATPase was investigated on frog neuromuscular preparations by recording the frequency augmentation-potentiation (FAP) of the endplate potential, an electrophysiological and neuropharmacological technique to analyze the drug actions on the release process of the readily releasable transmitter quanta. Erythrosin B, which was thought to selectively inhibit the neural type Na+, K(+)-ATPase, pivoted the log-linear FAP relation counterclockwise without altering the intercept on the ordinate. Chlormadinone had a similar action. An increase in the concentration of extracellular K+ ions pivoted the FAP relation clockwise with a concomitant upward shift of the intercept on the ordinate, and low K+ Ringer's solution produced an inverse effect. In contrast, Li+ ions shifted the FAP relation upwards dose-dependently leaving its slope unchanged. Cinnarizine, a blocker for inositol-1,4,5-trisphosphate-induced Ca2+ release, and 5,5'-dimethyl-1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid, a specific intracellular Ca2+ chelator, significantly antagonized the potentiating action of Li+. The ouabain-sensitive neural type Na+, K(+)-ATPase isozyme, which is abundant in neural tissues, seems to play an important role in stimulation frequency-dependent modulation of the quantal transmitter release such as FAP.

Adrenal Cortex Hormones↗

PubMed1995

Toxic and nontoxic effects of ouabain on the transmitter release from frog motor nerve terminals.

Toxic and nontoxic effects of ouabain were investigated on frog neuromuscular preparation by measuring the mean quantal content of endplate potentials elicited during repetitive nerve stimulation. In the untreated normal muscles, application of 10 microM ouabain gave rise to a slow exponential increase in the transmitter release (toxic ouabain effect) with a certain delay. This delay was increased with either 100 microM amiloride, a Na(+)-Ca2+ exchange blocker, or the intracellular loading of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a specific intracellular Ca2+ chelator. Measurements of frequency augmentation-potentiation (FAP) revealed a specific nontoxic effect of ouabain: 1 microM ouabain pivoted the long-linear FAP relation counter-clockwise without altering the intercept on the ordinate. Contrary to their action in the toxic effect, both 100 microM amiloride and the intracellular loading of BAPTA failed to counteract the nontoxic effect of 1 microM ouabain. The present results suggest that the toxic and nontoxic effects of ouabain are of different entities. The ouabain-sensitive subtype of Na+,K(+)-ATPase, which is abundant in neural tissues, seems to play a specific role in the process of nontoxic potentiation of transmitter release.

Amiloride↗

PubMed1995

Ruptured dissecting aneurysm of the peripheral anterior cerebral artery--case report.

A 27-year-old male presented with intracranial hemorrhage due to rupture of an idiopathic dissecting aneurysm in the A4 segment of the left anterior cerebral artery (ACA). This is a very rare location. He was successfully treated by resection of the aneurysm without neurological deficits. Surgical intervention is recommended for patients with intracranial hemorrhage due to ruptured dissecting aneurysm of the ACA to prevent rebleeding.

Adult↗

PubMed1995

[Treatment of acute promyelocytic leukemia--combined use of all-trans retinoic acid and granulocyte colony-stimulating factor].

We evaluated the effect of treatment by all-trans retinoic acid (ATRA) in 9 patients with acute promyelocytic leukemia (APL). Of 6 patients who had circulating leukemic blasts before treatment, 3 initially received ATRA alone but died of respiratory failure due to retinoic acid syndrome (RAS). High dose steroid therapy did not rescue RAS in these patients. Another 3 who were given intensive chemotherapy followed by ATRA and/or granulocyte colony-stimulating factor (G-CSF) achieved complete remission (CR). Of 3 patients without peripheral leukemic blasts before treatment, 1 received intensive chemotherapy followed by G-CSF and reached CR, 1 who had been previously given ATRA did not respond to ATRA, and 1 did not initially respond sufficiently to ATRA alone but responded dramatically to ATRA plus G-CSF. In the treatment of APL, appropriate combination of ATRA, G-CSF and chemotherapy should always be taken into consideration. In addition, RAS have to be carefully avoided when applying ATRA therapy in patients who have circulating leukemic blasts before treatment.

Adult↗

PubMed1995

[Continuous infusion therapy with low dose cytosine arabinoside and etoposide in acute myelogenous leukemia patients hardly tolerable for intensive combination chemotherapy].

We evaluated the efficacy of continuous drip infusion therapy with low dose cytosine arabinoside (AraC) and etoposide (VP16) in poor-condition patients with acute myelogenous leukemia (AML). Patients' age ranged from 19 to 85 years with a median of 63 years. Principally they received continuous drip infusion for 14 days with AraC (20 mg/day) and VP16 (50 mg/day). Complete remission (CR) rate was 58.3% (7/12) in untreated cases, 33.3% (2/6) in refractory cases to the standard chemotherapy, and 28.6% (2/7) in relapsed cases. The duration of CR ranged from 1.5 to 20 (+) months (median 8) in untreated group and from 2 to 22 months (median 10) in refractory and relapsed groups. Adverse effects such as gastroenterological symptoms appeared but were tolerable. Although infections due to myelosuppression appeared in 22 of 25 cases, they were well controlled by antibiotics. Chemotherapy-related death was not observed. Although CR rate and CR duration of this therapy were not sufficiently high, the regimen was effective in some patients with refractory or relapsed AML. Further studies are required to establish the efficacy, indication and safety of this treatment.

Adolescent↗

PubMed1995

[Clinical features of subacute interstitial pneumonia--clinico-pathological study based on open lung biopsy findings].

A clinico-pathological study was done to elucidate characteristic features of subacute interstitial pneumonia. The patients were four men and mine women, with a mean age of 60 years. In ten patients, the disease was idiopathic, three had collagen vascular disease, (and one was undergoing gold therapy for rheumatoid arthritis). The time interval between onset of symptoms and open lung biopsy was 80 +/- 40 days. Eleven patients had progressive dyspnea, seven had coughing, and only one complained of fever. Fine crakles were heard in ten patients. Mild increases in CRP were observed in all cases. Mild increases in total serum IgG concentration were observed in five of eight cases. Multiple patchy infiltration or diffuse interstitial shadows, located predominantly in the lower fields of both lungs were the characteristic chest roentgenographic findings. The average %VC was 62.7 +/- 17% and the average PaO2 was 68.3 +/- 10 Torr. Bronchoalveolar lavage was done in nine patients, and the mean total cell count was 16.5 +/- 10.2 x 10(4)/ml. A moderate increase in lymphocytes (30.8 +/- 18.6%) with a low CD4/8 ratio (0.48 +/- 0.57), a mild increase in neutrophils (6.2 +/- 9.1%), and a mild increase in eosinophils (2.3 +/- 3.7%) were observed. Pathologically, interstitial cellulo-fibrous changes associated with alveolar space closure due to organization of exudate were the main features. Patients were given steroid pulse therapy or oral steroids. The results were mild to marked improvements in chest roentgenographic findings and lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Sequence-specific DNA recognition by peptide heterodimers.

The DNA binding motif rich in basic amino acid residues is used by a variety of DNA binding proteins to recognize specific DNA sequences. We report here a sequence-specific DNA recognition by peptide heterodimers derived from the basic leucine zipper proteins. Specific hetero-dimerization is controlled by an artificial dimerization module consisting of a host-guest inclusion complex. Efficiency of the sequence discrimination by the peptide dimers depends on a stability of the half-matched binding complex. However, structures of the matched and half-matched binding complexes differ from one another.

Base Sequence↗

PubMed1994

Production of interleukin-10 by mouse glial cells in culture.

In this study, we examined the production of IL-10 by glial cells in vitro. IL-10 was detected in the culture supernatants of microglia and in the cell lysate of astrocytes by enzyme-linked immunosorbent assay. We also detected IL-10 mRNA and IL-10 receptor mRNA in both microglia and astrocytes. The expression of IL-10 mRNA, as well as the production of IL-10 protein, was enhanced by the stimulation of these cells with lipopolysaccharide(LPS). Recombinant IL-10 effectively suppressed both LPS-induced cytokine production and IFN-gamma-induced class II major histocompatibility complex antigen expression by microglia. These results suggest that IL-10 is produced in the CNS and plays a role as an inhibitory regulator in the CNS cytokine network.

Animals↗

PubMed1994

Inhibitory effect of vasoactive intestinal peptide (VIP) on phagocytosis in mouse peritoneal macrophages.

The effect of VIP on phagocytosis in peritoneal macrophages was examined by means of flow cytometry (FCM). This assay revealed that VIP suppressed phagocytosis in a dose-dependent manner. VIP(1-12) did not suppress phagocytosis. VIP(10-28) was more suppressive than VIP(1-28). A known VIP-antagonist (N-Ac-Tyr1,D-Phe2)-growth hormone-releasing factor (GRF) (1-29)-NH2 suppressed phagocytosis less than VIP. Control phagocytosis was partially suppressed in Ca(2+)-free solution. Phagocytosis was suppressed by VIP further in Ca(2+)-free solution than in the normal solution. Phagocytosis was suppressed in a known phosphodiesterase inhibitor IBMX-containing solution. The degree of suppression by VIP was the same in the presence or the absence of IBMX. These results suggest that VIP suppresses extracellular Ca(2+)-dependent and -independent phagocytosis, that the C-terminal fragment of VIP is essential for VIP action, that the suppression is mediated by cAMP and that the inhibition of macrophage phagocytosis by VIP is one of the mechanisms which modulates immune responses by the nervous system.

1-Methyl-3-isobutylxanthine↗

PubMed1994

Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1).

A cDNA encoding a novel member of the cytochrome P-450 superfamily, Cyp3a-13, has been isolated from mouse liver cDNA library by hybridization screening. The Cyp3a-13 encoded 503 amino acid residues and shared 71% amino acid identity with Cyp3a-11. When Cyp3a-13 cDNA was expressed in CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P-450 reductase cDNA of guinea pigs, aflatoxin B1-dependent cytotoxicity was observed. This cytotoxicity was enhanced by alpha-naphthoflavone (7,8-benzoflavone), which is known to augment the CYP3A enzymatic activity. The results indicate that CYP3A in mice, which are relatively insensitive to aflatoxin B1, can activate aflatoxin B1 to a genotoxic product.

Aflatoxin B1↗

PubMed1994

Implantation and growth of epidermal growth factor (EGF) receptor expressing human ovarian cancer xenografts in nude mice is dependent on EGF.

BACKGROUND: The importance of epidermal growth factor (EGF) receptor-dependent growth has not been clarified for in vivo growth of primary human ovarian cancers. METHODS: Seventeen primary human ovarian cancer tissue samples were examined for the presence of EGF receptors by a 125I-EGF-binding study. Three groups of mice were inoculated with EGF receptor expressing and not-expressing cancer tissues. The groups were as follows: control group, Sx group (mice that underwent sialoadenectomy; EGF depleted mice), and Sx+EGF (EGF-replaced) group. The ability of the inoculated tissues to implant and grow then was studied. RESULTS: Of the 17 primary ovarian cancers, 12 expressed EGF receptors and 5 did not. Eight of 12 EGF-receptor expressing cancer tissues implanted and formed growing tumors in control animals. None implanted in the Sx animals. Epidermal growth factor receptor-expressing cancers implanted in Sx animals that received EGF administration. Two of five EGF receptor-negative ovarian cancers implanted and grew in both control and Sx animals. CONCLUSION: Growth of EGF receptor-expressing primary human ovarian cancers may be dependent on EGF in vivo.

Animals↗

PubMed1994

Developmentally regulated expression of a murine receptor-type protein tyrosine phosphatase in the thymus.

Reversible phosphorylation of tyrosine residues plays a crucial regulatory role in various cellular events, including differentiation and proliferation of lymphocytes. Here, we report the isolation of a murine receptor-type protein tyrosine phosphatase (PTP), mRPTP-sigma, which is expressed in both immature thymocytes and stroma cells. At least two alternatively spliced transcripts of mRPTP-sigma (T and B) were observed. mRPTP-sigma T was the dominant form in the thymus and had three Ig-like and eight fibronectin type III-like domains in the extracellular portion. mRPTP-sigma T was almost identical with RPTP-sigma/PTP NE-3/PTP-P1/CPTP1, a PTP recently cloned from rat brain, except that RPTP-sigma/PTP NE-3/PTP-P1 was about 400 amino acids shorter than mRPTP-sigma T. mRPTP-sigma B, the second form of mRPTP-sigma, was dominant in the brain and was most likely the murine counterpart of RPTP-sigma/PTP NE-3/PTP-P1. In the developing thymocytes, the expression of mRPTP-sigma was high in double negative (CD4-CD8-), low in double positive (CD4+CD8+), and marginal in single positive (SP; CD4+CD8- or CD4-CD8+) subpopulations. No upregulation of mRPTP-sigma was observed in the spleen cells stimulated with Con A. Developmental regulation of mRPTP-sigma expression suggests its involvement in the control of T lymphocyte differentiation.

Alternative Splicing↗

PubMed1994

Expression of cytokines during glial differentiation.

Astrocytes and microglia produce a variety of cytokines, some of which may have roles in the proliferation and differentiation of glial cells during development in the central nervous system. Cytokine mRNAs and activities were therefore assayed during glial development in mixed glial cell cultures from newborn mouse brain. Cytokine mRNAs were also measured in mouse brain during postnatal development in vivo. Macrophage colony-stimulating factor(M-CSF) mRNA, interleukin-1 beta (IL-1 beta) mRNA and tumor necrosis factor alpha (TNF alpha) mRNA were all detected on the in vitro cultures and each showed a distinct time course of expression. IL-6 and granulocyte-macrophage colony-stimulating factor(GM-CSF) mRNAs were not detected in the cultured cells. Measurements of cytokine activity in culture supernatants as well as cytokine mRNAs in vivo gave similar results. The data suggest that IL-1, TNF alpha and M-CSF are produced in the period of gliogenesis, and that M-CSF rather than GM-CSF may promote the generation and proliferation of microglia. Although IL-6 and GM-CSF exhibit neurotrophic effects, these cytokines may not function as neurotrophic factors during early postnatal development.

Animals↗