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Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 451 records · Page 25Linked to original sources
PubMed1986

(6R)-tetrahydrobiopterin increases the activity of tryptophan hydroxylase in rat raphe slices.

The effects of (6R)- and (6S)-tetrahydrobiopterin (BPH4), tetrahydroneopterin, and 6-methyltetrahydropterin on the activity of tryptophan hydroxylase were investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measurement of 5-hydroxytryptophan (5-HTP) formation under inhibition of aromatic L-amino acid decarboxylase with use of HPLC-fluorometric detection. (6R)-BPH4 (the naturally occurring form) at 42 microM, tetrahydroneopterin at 50 microM, and 6-methyltetrahydropterin at 100 microM increased tryptophan hydroxylase activity to 350, 145, and 146% of control values, respectively. (6S)-BPH4, however, had no significant effects on tryptophan hydroxylase activity. These results suggest that tryptophan hydroxylase is subsaturating in vivo for the naturally occurring cofactor, (6R)-BPH4, and that the concentration of (6R)-BPH4 may play an important role for the regulation of tryptophan hydroxylase activity in vivo.

5-Hydroxytryptophan↗
PubMed1986

Stimulation of the serotonin autoreceptor prevents the calcium-calmodulin-dependent increase of serotonin biosynthesis in rat raphe slices.

The role of the serotonin (5-hydroxytryptamine) autoreceptor in the regulation of the activity of tryptophan hydroxylase was investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measuring the accumulation of 5-hydroxytryptophan in the presence of inhibition of aromatic L-amino acid decarboxylase using 3-hydroxy-4-bromobenzyloxy-amine by HPLC with fluorescence detection. Serotonin and its agonists N,N-dimethyl-5-methoxytryptamine and 1-(m-chlorophenyl)-piperazine reduced the formation of 5-hydroxytryptophan to 50-60% at 10(-5) M. The effect of serotonin was reversed by 10(-5) M methiothepin, an antagonist of the serotonin autoreceptor. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), dose-dependently reduced the basal formation of 5-hydroxytryptophan to 40-50% at 10(-6) and 10(-4) M, respectively. W-7 also reduced the activated formation by A-23187 or dibutyryl cyclic AMP in a dose-dependent manner. W-7 had no effect on 5-hydroxytryptophan formation reduced by serotonin at 10(-5) M. These results suggest that the role of the serotonin autoreceptor was related to the prevention of the calcium-calmodulin-dependent activation of tryptophan hydroxylase.

5-Hydroxytryptophan↗
PubMed1986

Role of the naphthoquinone moiety in the biological activities of sakyomicin A.

The naphthoquinone moiety was proven to be essential to the biological activities of sakyomicin A using various naphthoquinone derivatives. Among the naphthoquinones tested, juglone (5-hydroxy-1,4-naphthoquinone) which resembles the partial structure of sakyomicin A was the most active in cytotoxicity against murine lymphosarcoma L5178Y cells, electron acceptor function in the oxidation of NADH by Clostridium kluyveri diaphorase or rat liver mitochondria and inhibition against avian myeloblastosis virus reverse transcriptase. The significantly lower cytotoxicity of sakyomicin A as compared with juglone was attributable to its poor membrane transport. The inhibition of reverse transcriptase activity may result from the interaction between a sulfhydryl group in the active center of the enzyme and quinone groups of the naphthoquinones and sakyomicin A.

Animals↗
PubMed1986

Serum monoclonal IgM undetectable by cellulose acetate membrane electrophoresis in four patients with B cell malignant lymphoma.

A small amount of monoclonal IgM was demonstrated in the serum of four B cell malignant lymphoma patients in whom electrophoretically homogeneous protein bands were not detected by either cellulose acetate membrane electrophoresis or immunoelectrophoresis. By using anti-idiotypic (Id) antisera prepared against serum IgM, the M proteins were detected and identified as the products of malignant cells. These findings suggest that the use of more sensitive technics than the usual serum electrophoresis shows that the incidence of M proteins in B cell malignant lymphomas is higher than has been previously reported.

Adult↗
PubMed1986

Monoclonal anti-idiotypic antibodies against monoclonal rheumatoid factors derived from patients with Sjögren's syndrome.

Monoclonal anti-idiotypic antibodies (mA-IDs) were produced against IgM-K, IgA-L and IgA-K monoclonal rheumatoid factors (mRFs), respectively, derived from patients with Sjögren's syndrome (SS). Each mA-ID inhibited the RF activity of the autologous M-protein, but did not inhibit the activity of the other mRFs. As for the specificity of mA-IDs, it was confirmed to bind only to the mRF used for immunization. A cross-reactive idiotype (CRI) was detected in 3 out of 106 polyclonal RFs (pRFs) using AW5/3 mA-ID by double immunodiffusion or ELISA inhibition assay on pRF activity. However, no CRI was detected on AMB1/5 or SF18/2 mA-ID. One of the mA-IDs, AW5/3, cross-reacted with nuclei of proliferating lymphocytes, such as PHA-stimulated lymphocytes, interleukin 2 dependent T cell lines, B-lymphoblastoid cell lines or cultured lymphoma cell lines, but barely reacted with nuclei of normal resting lymphocytes.

Antibodies, Anti-Idiotypic↗
PubMed1985

Localization of [3H]serotonin in neuroblastoma x glioma hybrid cells.

Synthesis, localization and release of serotonin (5-HT) were studied in cholinergic neuroblastoma X glioma NG108-15 cells. The content of 5-HT and tryptophan hydroxylase activity rose substantially when hybrid cells were differentiated by prostaglandin E1 plus theophylline, or dibutyryl cAMP. Localization of [3H]5-HT taken up into differentiated NG108-15 cells was examined by electron microscopic radioautography. Silver grains were observed mostly in neurites, indicating that neurites of differentiated NG108-15 cells are the preferential uptake site of [3H]5-HT. Statistical analysis of the results of electron microscopic radioautographs revealed that silver grains had a high affinity for dense core vesicles of 60-170 nm diameter, though grains were also located over endoplasmic reticulum, mitochondria and cytosol. Dense core vesicles were abundant in neurites, and less numerous in cell bodies of the hybrid cells. [3H]5-HT taken up into NG108-15 cells was released by potassium stimulation in the presence of Ca2+. The results indicate that NG108-15 hybrid cells manifest many properties comparable to those of serotonergic neurons.

Animals↗
PubMed1985

Excitatory effect of amino acids on identified neuron R14 of Aplysia. I. Glycine-induced depolarization and its ionic mechanism.

The ionic mechanism of the membrane effect of glycine on identified neuron R14 of Aplysia was investigated with conventional intracellular recording and voltage-clamp techniques. Both localized and bath applications of glycine markedly depolarize R14. Bath-applied glycine induced an inward current that gradually reached a maximum and remained at that level until glycine was washed out. Displacement of the holding potential from -46 to -121 mV increased the inward current. The extrapolated reversal potential was +38.6 mV. Reduction of [Na+]o reversibly decreased the inward current. Alterations of [K+]O, [Cl-]O, and [Ca2+]O, as well as bath-applied ouabain and sodium cyanide, did not affect the inward current. These results suggest that glycine can induce an Na+ current and that the glycine-induced inward current does not reflect an active uptake by an Na+-coupled transport system of glycine into the neuron.

Animals↗
PubMed1985

Tryptophan hydroxylase activity in the brains of controls and parkinsonian patients.

The activity of tryptophan hydroxylase was measured in nine regions of human brains from controls and patients with Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome and progressive supranuclear palsy by high performance liquid chromatography with fluorescence detection. The regional distribution of the enzyme activity in control brains was similar to that of serotonergic neurons; relatively high activity was found in the raphe nucleus, locus coeruleus and substantia nigra. The activity in the thalamus in Parkinson's disease and that in the locus coeruleus, raphe nucleus and substantia nigra in striato-nigral degeneration were significantly lower than that of controls (p less than 0.05). In most other brain regions in parkinsonian patients the activity was relatively lower than that of controls except the caudate nucleus and nucleus accumbens where the activity was relatively higher than that of controls. Marked decrease in the enzyme activity in various brain regions was observed in striato-nigral degeneration, Shy-Drager syndrome, and progressive supranuclear palsy. These results suggest that the activity of tryptophan hydroxylase in serotonergic neurons is reduced in the brains of parkinsonian patients and of patients with degenerative nervous diseases.

Adolescent↗
PubMed1985

Enzyme-immunoassay of thromboxane B2 at the picogram level.

A highly sensitive and reproducible enzyme-immunoassay for the measurement of thromboxane B2 was developed. Thromboxane B2 (TxB2) was coupled with beta-D-galactosidase by mixed anhydride reaction. Thromboxane B2-antiserum was generated in rabbits and used at a final dilution of 1:480,000. The separation of immunocomplex from the free form of TxB2 was accomplished by the double antibody method. The second antibody was sheep anti rabbit IgG. The precipitated enzyme activity was measured fluorometrically with 4-methyl-umbelliferyl-beta-D-galactoside as substrate. This method allowed to measure TxB2 in the range of 0.002-5 picomole per tube. The cross-reactivity of the anti-thromboxane B2-antiserum with 2,3-dinor thromboxane B2 was about 20%, but it was less than 0.2% for the other prostanoids tested. TxB2 extracted from human urine was measured by enzyme-immunoassay (y) and radioimmunoassay (x) which has been found closely correlated to values obtained by gas chromatography-mass spectrometry. Regression analysis of the data comparing enzyme-immunoassay and radioimmunoassay gave the equation y = 0.996 x + 0.470, correlation coefficient r = 0.9947. Inter-assay coefficient of variation was 3.1%. The assay was further simplified by coating the second antibody on glass beads. The regression equation between this solid-phase enzyme immunoassay (y) and radioimmunoassay (x) was y = 0.9860 X 1.927, r = 0.9895, and enzyme immunoassay (y) was y = 0.9749 X -0.94808, r = 0.9887. Thus, the enzyme-immunoassay shows specificity and sensitivity comparable to radioimmunoassay making use of radioactive tracer unnecessary.

Cross Reactions↗
PubMed1985

Cisplatin, vinblastine, and bleomycin therapy of yolk sac (endodermal sinus) tumor of the ovary.

Five patients with yolk sac (endodermal sinus) tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin combination therapy (PVB). Four of five achieved a complete remission and remain free from disease 24 to 53 months from start of PVB therapy. One patient did not respond well to PVB and died 11 months after start of PVB therapy. One patient who was treated with PVB after unilateral salpingo-oophorectomy has delivered a normal term infant. Serum alpha-fetoprotein levels were monitored in all patients during and after therapy. Serum alpha-fetoprotein was correlated with clinical course.

Adolescent↗
PubMed1985

Establishment of a new ovarian tumor line in nude mice and its application to treatment of the donor patient.

A new line of the human ovarian tumor (poorly differentiated adenocarcinoma), designated OVA-2, has been established by heterotransplantation of the original tumor into athymic nude mice. The donor patient, a 38-year-old woman with stage IV disease, was treated with cis-diamminedichloroplatinum II, Adriamycin, 5-fluorouracil, and VM-26, which were selected in consideration of the results, obtained by experimental chemotherapy of this heterotransplanted tumor. She achieved a complete remission and is alive 15 months after diagnosis. Usefulness of the human tumor-nude mouse system in chemotherapy is reemphasized.

Adenocarcinoma↗
PubMed1985

Association of lipid peroxidation during luteal regression in the rat and natural aging in the rotifer.

Lipid peroxides (LP) were measured in whole homogenates and membrane fractions from luteinized rat ovaries and in homogenates of aging rotifers. There was a significant increase in the accumulation of LP as plasma progesterone levels declined during luteal regression. Lipid peroxide levels also increased with age in rotifers. This study indicates that lipid peroxide accumulation is associated with cellular breakdown and suggests that the rat corpus luteum may be used as a mammalian aging model.

5'-Nucleotidase↗
PubMed1985

Dexamethasone effect on prostanoid formation in healthy man.

1. Dexamethasone was administered to six healthy female volunteers for 4 days, resulting in plasma levels of 4.8 +/- 1.4 x 10(-8) mol/l. Urinary excretions of six prostanoids as well as collagen-induced platelet thromboxane formation and aggregation were determined before, during and 1 month after administration of dexamethasone. 2. Dexamethasone had no effect on urinary thromboxane B2 (77 +/- 22 ng/day vs 63 +/- 16 ng/day during dexamethasone), dinor-thromboxane B2, the major urinary metabolite of thromboxane B2 (406 +/- 84 ng/day vs 380 +/- 90 ng/day), dinor-6-keto-prostaglandin F1 alpha, the major urinary metabolite of prostacyclin (199 +/- 41 ng/day vs 237 +/- 53 ng/day), tetranor-5,11-diketo-7 alpha-hydroxy-prostane-1,16-dioic acid, the major urinary metabolite of prostaglandins E1 and E2 (7712 +/- 1677 ng/day vs 7886 +/- 2565 ng/day) and tetranor-11-keto-5 alpha,7 alpha-dihydroxy-prostane- 1,16-dioic acid, the major urinary metabolite of prostaglandins F1 alpha and F2 alpha (14,394 +/- 2053 ng/day vs 18,288 +/- 2251 ng/day). Prostaglandin E2 excretion slightly but significantly increased from 217 +/- 48 ng/day to 294 +/- 55 ng/day. Collagen-induced platelet thromboxane formation and aggregation were not altered. 3. These results suggest that glucocorticoids do not regulate renal, platelet or total body prostanoid formation in healthy man.

Adult↗
PubMed1985

Serum immunosuppressive acidic protein in adult T-cell leukaemia (ATL).

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T-cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 +/- 502.4 micrograms/ml) than in those with atypical ATL (426.7 +/- 106.6 micrograms/l), smoldering ATL (310.0 +/- 51.3 micrograms/ml), healthy carriers of ATLA antibody (302.9 +/- 39.5 micrograms/ml) and normal controls (350.5 +/- 73.2 micrograms/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P less than 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.

Adult↗