Biomedical subjects

M Sawada

Publications and source records attributed to M Sawada.

At least 361 records · Page 20Linked to original sources

PubMed1990

Extracellular tumor necrosis factor induces a decreased K+ conductance in an identified neuron of Aplysia kurodai.

Recombinant human tumor necrosis factor (rhTNF) was pressure-applied onto the the soma of identified neuron R12 in the Aplysia abdominal ganglion. rhTNF induced a slow inward current (ITNF, 80-100 s in duration, 5-10 nA in amplitude) associated with a conductance decrease. ITNF begins 1-2 s after applying rhTNF and peaks in 5-6 s. ITNF was decreased by hyperpolarization and had a reversal potential of approximately -87 mV (close to the K+ equilibrium potential). Ion substitution and pharmacological experiments suggest that ITNF is due to a decreased K+ conductance and that TNF, a product of macrophages, may form an important link in communications between nervous and immune systems.

Animals↗

PubMed1990

Activation of single Ca2(+)-dependent K+ channel by external ATP in mouse macrophages.

Single Ca2(+)-dependent K+ currents responding to external ATP were recorded from cell-attached patches on mouse peritoneal macrophages. Extracellularly applied ATP activated an inward single-channel current with a conductance of 25 pS and a reversal potential of -79 mV (pipette potential, Vp) when the pipette contained a 145 mM KCl solution. The reversal potential was shifted 56 mV positive by a 10-fold reduction in external (pipette) K+ concentration. The effect of ATP was abolished by either removal of external Ca2+ or treatment with an intracellular Ca2+ chelator, the acetoxymethyl ester of 1,2-bis (2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA-AM). This channel has a mean open time of 9.1 ms and open probability was not strongly dependent on Vp in the range tested (+120 to -30 mV).

Adenosine Triphosphate↗

PubMed1990

Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes.

We investigated the production of interleukin-3 (IL-3)-like factor by murine astrocytes. Supernatants from lipopolysaccharide (LPS)-stimulated astrocytes induced proliferation of IC-2, an IL-3- and granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent cell line. This activity was completely neutralized by the antibody against GM-CSF but not by the anti-IL-3 monoclonal antibody. Northern blot analysis revealed the expression of GM-CSF mRNA, but not of IL-3 mRNA, in cultured astrocytes. These results indicate that with proper stimuli murine astrocytes produce GM-CSF.

Animals↗

PubMed1990

[A clinicopathological study of pulmonary metastases in carcinoma of the uterine cervix].

Carcinoma of the uterine cervix was evaluated in 1,121 patients at Kure National Hospital, Hiroshima, between 1969 and 1987. The patients were retrospectively evaluated for the presence of pulmonary metastases. On chest radiography, 35 patients were found to have metastases. Pulmonary metastases were seen in 3.1% of patients with carcinoma of the cervix. Thirty-two patients out of 35 could be evaluated about their clinical stage, histology, and disease course: 3 patients were classified into stage Ib, 10 were stage II, 15 were stage III, and 4 were stage IV. Histologically, 27 patients were squamous cell carcinoma, 2 were adenocarcinoma, and 3 were others. Mean interval from initial disease staging to detection of lung metastases was 17.1 months. Once pulmonary spread was discovered, half of them expired within 4 months. Twenty-two patients had other focus of metastasis besides lung.

Adenocarcinoma↗

PubMed1990

Activation of a non-specific cation conductance by intracellular injection of inositol 1,3,4,5-tetrakisphosphate into identified neurons of Aplysia.

The ionic mechanism of the effect of intracellularly injected inositol 1,3,4,5-tetrakisphosphate (IP4) on the membrane of identified neurons (R9-R12) of Aplysia kurodai was investigated with conventional voltage-clamp, pressure injection, and ion-substitution techniques. Intracellular injection of IP4 into a neuron voltage-clamped at -45 mV reproducibly induced a slow inward current (20-60 s in duration, 3-5 nA in amplitude) associated with a conductance increase. The current was decreased by depolarization and increased by hyperpolarization. The extrapolated reversal potential was -21 mV. The IP4-induced inward current was sensitive to changes in the external Na+, Ca2+ and K+ concentration but not to changes in Cl- concentration, and was resistant to tetrodotoxin (50 microM). When the cell was perfused with tetraethylammonium (5 mM) but not with 4-aminopyridine (5 mM), the IP4-induced inward current recorded at -45 mV slightly increased. The IP4-induced inward current was partially reduced by calcium channel blockers (Co2+ and Mn2+). These results suggest that intracellularly injected IP4 can activate a non-specific cation conductance.

Animals↗

PubMed1990

Estrogen- and androgen-responsive growth of human ovarian adenocarcinoma heterotransplanted into nude mice.

A new line of human serous cystadenocarcinoma of the ovary, designated OVA-5, has been established in athymic nude mice. A strong correlation was noted between tumor volume and plasma CA125 levels in mice bearing OVA-5 tumor. Growth of the OVA-5 tumor in castrated male nude mice was accelerated by s.c. administration of estradiol-17 beta and 5 alpha-dihydrotestosterone but not by progesterone. Estradiol-17 beta and 5 alpha-dihydrotestosterone also accelerated the growth of the OVA-5 tumor heterotransplanted into sialoadenectomized castrated male nude mice. No remarkable change was observed in the histological appearances of the tumors between control groups and hormone-treated groups. Receptor assays revealed that the OVA-5 tumor had both estrogen and androgen receptors. Growth of the OVA-5-tumor is thus responsive to estrogen and androgen.

Adenocarcinoma↗

PubMed1990

Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C.

Microglia were isolated from primary mixed brain cell culture of normal newborn mice and then cultivated. They were able to be maintained in vitro for 1-2 months, but incorporated little [3H]thymidine under normal culture conditions. When treated with the conditioned medium of L929 mouse fibroblast cells as a crude CSF-1 (mouse macrophage-colony stimulating factor) or purified CSF-1, microglia showed morphological changes and increased in both cell number and [3H]thymidine uptake. In addition, crude CSF-1 increased lysosomal enzyme activity and superoxide anion formation of microglia up to 2 and 3.8 fold as control value, respectively. These effects of CSF-1 were not observed in the purified astrocyte culture. Purified microglia had CSF-1 receptors which were recognized by the anti-CSF-1 receptor antibody that arose from a peptide of a product of proto-oncogene, c-fms. 12-O-Tetradecanoylphorbol-13-acetate (TPA) also increased microglia cell number and their biochemical activities, suggesting the possible involvement of protein kinase C activation. Protein kinase inhibitors, such as staurosporine or H-7, inhibited the effects of both CSF-1 and TPA. These results indicate that microglia may be regulated in its biochemical and proliferation activities by CSF-1 and that this may occur via activation of protein kinase C.

Animals↗

PubMed1990

DNA autosensitivity in two Japanese sisters.

Two cases of DNA autosensitivity in Japanese sisters are reported. Both patients developed painful ecchymoses and other bleeding disorders. Skin tests with autologous leukocyte lysates and calf thymus DNA produced intermediate-type reactions that were identical to spontaneous skin reactions. Pretreatment of DNA with either DNase or chloroquine sulfate inhibited these reactions. Our studies suggest that anti-DNA antibodies might contribute to the clinical symptoms of this disorder.

Adult↗

PubMed1990

Biochemical changes associated with the mechanism controlling superoxide radical formation in the aging rotifer.

Levels of the superoxide radical (SOR) and lipid peroxides were measured and found to increase during aging in the short-lived rotifer, Asplanchna brightwelli. Life-span was altered by changes in environmental temperature, absence of light, diet restriction, exposure to ultraviolet radiation, and addition of vitamin E to the diet. Each of the conditions that lengthened life-span decreased SOR and lipid peroxide levels, and each condition that shortened life-span increased levels of SOR and lipid peroxides. Additional experiments indicated that on the third day of age, there was a significant increase in Ca2+ uptake and phospholipase A2 activity in membrane samples and an elevation in superoxide dismutase and catalase activity in rotifer homogenates. In addition, SOR concentration was inhibited by the addition of bromophenacyl bromide and indomethacin to membrane samples. By day 5 there was also a significant increase in the lysosomal enzyme, alpha-mannosidase. The results of this study indicate that levels of the SOR and lipid peroxides are coupled to rotifer life-span and that activation of phospholipase A2 may contribute to the elevation of these agents in older animals.

Adenosine Triphosphate↗

PubMed1990

Tyrosine hydroxylase, tryptophan hydroxylase, biopterin, and neopterin in the brain of anorexia nervosa.

The activities of tyrosine hydroxylase and tryptophan hydroxylase and contents of biopterin and neopterin were measured for the first time in various regions of human brain from a patient with anorexia nervosa (AN). In AN as compared with controls, tyrosine hydroxylase activity was markedly reduced in all brain regions analyzed, while tryptophan hydroxylase activity and biopterin content had a tendency to increase. Neopterin content did not change dramatically. The opposite changes of tyrosine hydroxylase and tryptophan hydroxylase suggest an imbalance between the activity of catecholaminergic neurons and that of serotonergic neurons, and may be related to pathogenesis of AN.

Adult↗

PubMed1990

OKY-046 inhibits anaphylactic bronchoconstriction and reduces histamine level in bronchoalveolar lavage fluid in sensitized guinea pigs.

We investigated the effects of OKY-046, a potent and selective thromboxane A2 (TxA2) synthetase inhibitor, on anaphylactic bronchoconstriction and release of chemical mediators into airway lumen in sensitized guinea pigs in vivo. OKY-046 dose-dependently inhibited antigen-induced anaphylactic bronchoconstriction with or without mepyramine, a histamine H1 antagonist. In the presence of mepyramine, OKY-046 (300 mg/kg, p.o.) elicited significant reductions in histamine (1 min) and TxB2 increases (1-15 min) in bronchoalveolar lavage (BAL) fluid but significantly increased the plasma level of 6-keto-PGF1 alpha, a stable PGI2 metabolite, after antigen challenge. On the contrary, indomethacin only significantly reduced increases in TxB2 levels. These results suggest that the antiasthmatic effect of OKY-046 is probably due to inhibition of TxA2 synthesis and suppression of histamine release via a PGI2 shunting mechanism.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

A comparison of chromosome aberration induction by 25 compounds tested by two Chinese hamster cell (CHL and CHO) systems in culture.

Twenty-five chemicals were tested for the induction of chromosomal aberrations in 2 cultured mammalian cell systems, Chinese hamster lung cells (CHL) and Chinese hamster ovary cells (CHO). This study was carried out to provide a data set that would permit an assessment of the extent to which the 2 systems agree in the results produced. Results presented for the 2 systems in this paper are not based on the same criteria but rather on the criteria standardly used in each of the systems. In tests conducted in the absence of S9 mix, 7 chemicals gave positive results in both systems and 12 were negative in both. In tests with S9 mix, 5 were positive in both systems and 9 were negative in both. When the overall results including tests both with and without S9 mix were considered, the 2 systems agreed on 15 results, 11 positives and 4 negatives. A review of the test conditions and data suggests that disagreements in test results were more often due to differences in the protocols used in these 2 systems than to a difference in the sensitivities of the 2 cell lines.

Animals↗

PubMed1990

Effects of colony stimulating factors on isolated microglia in vitro.

Effects of colony stimulating factors (CSF), known regulators for cells in monocytic lineage, on isolated microglia were examined. Interleukin-3 (IL-3) induced only morphological changes in rod-shaped microglia, while granulocyte-macrophage CSF (GM-CSF) and CSF-1 induced both morphological changes and proliferation of microglia. CSF-1 also activated the enzyme activity of microglia. These observations indicated that, in terms of regulation by cytokines, microglia are similar to mature cells in monocytic lineage. Although astrocytes reportedly produce IL-3 and GM-CSF, the effects of astrocyte-conditioned medium (Ast-Sup) were different from those of either IL-3 or GM-CSF. Ast-Sup caused ameboid microglia to become ramified, and did not induce proliferation of microglia. Factors from astrocytes may have a role in the transformation of microglia which occurs in either normal developing brain or inflammation in the brain.

Animals↗

PubMed1990

Extracellular ATP activates Ca2(+)-dependent K+ conductance via Ca2+ influx in mouse macrophages.

1. Using the perforated patch recording, the effects of ATP on membrane current were investigated in mouse peritoneal macrophages. 2. Extracellularly applied ATP induced a biphasic current consisting of a initial inward current [Ii(ATP)] followed by an outward current [Io(ATP)]. These currents were associated with a marked increase in conductance at their peaks. 3. Ii(ATP) reversed close to 0 mV and was attenuated by removal of external Na+. 4. Io(ATP) reversed near -80 mV and was increased by decreasing the external concentration of K+. 5. Io(ATP) was completely abolished by removal of external Ca2+, treatment with an intracellular Ca2+ chelator, the acetoxymethyl ester of 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetra acetic acid (BAPTA-AM) and bath applied quinidine but not tetraethylammonium (TEA) or apamin. 6. These results suggest that Ii(ATP) and Io(ATP) are due to an activation of nonspecific cationic and Ca2(+)-dependent K+ conductances, respectively, and raise the possibility that the putative ATP receptor may be important in regulating macrophage functions, motility, phagocytosis and cytokines secretion.

Adenosine Triphosphate↗

PubMed1990

Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2.

The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA1 greater than 11% excreted less KAL. Urinary PGE2 excretion (7.6 +/- 2.8 ng/mg creatinine, mean +/- SE) was significantly lower in DM compared to C (17.5 +/- 3.9, p less than 0.05), while DM excreted more TXB2 (0.57 +/- 0.09, p less than 0.01) and 2,3-dinor-TXB2 (0.56 +/- 0.12, N.S.) than C (0.19 +/- 0.02 or 0.33 +/- 0.01). DM with or without mild proteinuria demonstrated lower PGE2, but higher TXB2 and 2,3-dinor-TXB2 excretion. A positive correlation of TXB2/2,3-dinor-TXB2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 micrograms/mg creatinine, TXB2 and 2,3-dinor-TXB2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB2 to PGE2 or 2,3-dinor-TXB2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB2 to 2,3-dinor-TXB2 may indicate an augmented renal, in addition to platelet, TXA2 synthesis. An excessive vasoconstrictive and proaggregatory TXA2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE2, may have profound effects on renal functions such as protein excretion in DM.

Adult↗

PubMed1990

Dietary treatment ameliorates overt diabetes and decreased insulin secretion to glucose, induced by overeating in impaired glucose tolerant mice.

Overt diabetes (NIDDM) was induced by overeating in neonatally streptozocin (60 mg/kg.BW) treated impaired glucose tolerant mice. We imposed a food restriction and a high fiber diet to evaluate the effects of dietary treatment in this NIDDM model mouse. Furthermore, insulin secretion after the dietary treatment was studied using the perfused pancreas technique. One group of IGT mice (SZ) was maintained on ordinary mouse chow during 6 to 14 weeks of age. The others received a cookie and chocolate mashed diet (C.C. diet) to induce overt diabetes during 6 to 10 weeks of age. Thereafter, the mice with induced overt diabetes were divided according to their diet treatment. The C.C. diet was continued in one group (SZC) for 4 weeks, and the others were divided into a food restriction group (SZR: 4 g/mouse/day of ordinary mouse chow, for 4 weeks) and a high fiber diet group (SZF: 20% W/W of cellulose in ordinary mouse chow, for 8 weeks). The mean caloric intake/mouse/day in SZC, SZR and SZF were 140, 80 and 98% of that in SZ, respectively. Amelioration of hyperglycemia and impaired glucose tolerance was noted in SZR and SZF. A better glycemic control was obtained in SZF with keeping a normal growth rate. On the pancreas perfusion, the insulin secretion to 30 mM glucose was improved in SZR and SZF. Furthermore, the incremental first phase peak insulin release to 30 mM glucose in SZF was significantly greater than that in SZC (SZF, 10.5 +/- 1.0 vs. SZC, 4.5 +/- 1.9 microU/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

A case of ovarian cystadenocarcinoma associated with pregnancy.

A case of ovarian cystadenocarcinoma associated with pregnancy is reported. The semicystic left ovarian tumor was found in a 28-year-old woman, gravida 2, para 1 at 33 weeks' gestation. A primary Cesarean section, total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy were performed. The histological examination revealed the tumor to be a serous cystadenocarcinoma. The patient and infant have both remained well and free of disease for the eight years which have elapsed since the therapy started.

Adult↗

PubMed1990

Contribution of prostacyclin to D-tubocurarine-induced hypotension in humans.

In order to evaluate the role of prostacyclin in d-tubocurarine-induced hypotension in human, the authors examined the relationship of changes of arterial blood pressure and plasma 6-keto-PGF1 alpha level following iv administration of d-tubocurarine (dTc), with or without prior administration of aspirin and H1 antagonist. The bolus injection of dTc 0.6 mg/kg caused a significant decrease in mean arterial pressure (MAP) that was associated with a significant increase in plasma 6-keto-PGF1 alpha (P less than 0.05 in both). The maximum MAP decrease and plasma 6-keto-PGF1 alpha increase were noted at 2 min after dTc administration. Pretreatment with aspirin DL-lysine (25 mg/kg) or diphenhydramine (1 mg/kg) significantly attenuated the responses of MAP (P less than 0.05 in both) and plasma 6-keto-PGF1 alpha level (P less than 0.01 for aspirin group, P less than 0.05 for diphenhydramine group). There was a significant correlation between the changes in plasma 6-keto-PGF1 alpha and those in MAP (Kendall tau (tau) = -0.504, P less than 0.01). These findings suggest that a bolus injection of dTc induces a release of prostacyclin through H1 receptor, which is responsible for the dTc-induced transient decrease of blood pressure in humans.

6-Ketoprostaglandin F1 alpha↗