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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 577 records · Page 32Linked to original sources
PubMed1987

Detection of Tn antigen with Vicia villosa agglutinin in urinary bladder cancer: its relevance to the patient's clinical course.

Recently, several investigators have demonstrated that the MN blood group precursor antigens Thomsen-Friedenreich antigen (T-Ag) and Tn-antigen (Tn-Ag) are expressed on the cell surfaces of several cancers, including urinary bladder cancer. T-Ag is composed of a specific carbohydrate chain, galactose-beta-1-3-N-acetylgalactosamine (GalNAc), which is specifically detectable through the immunohistochemical binding of peanut agglutinin (PNA). In normal cells, T-Ag is cryptic (cT-Ag) and can be unmasked by treatment with neuraminidase. Tn-Ag is composed of another carbohydrate chain, alpha-GalNAc-serine/threonine, and binds specifically to Vicia villosa agglutinin (VVA). With the use of both these lectins, VVA and PNA, the presence or absence of Tn-Ag and T-Ag was examined in 24 specimens of normal bladder epithelium and specimens from 53 cases of human urinary bladder transitional cell carcinoma of various histologic grades by staining paraffin sections by means of the avidin-biotin-immunoperoxidase technique. The correlation between the expression of these antigens and the patient's clinical course was then estimated. Out of 21 patients in whom the tumors expressed the phenotype Tn-Ag(+), T-Ag(+), or cT-Ag(-), 17 suffered from invasive recurrence. Although patients with tumors expressing the phenotypes T-Ag(-) and cT-Ag(+) have been reported to show a good clinical course, in our studies some of them showed a switch to invasive recurrence. Thus it was not possible to estimate the patient's clinical course only by the presence or absence of T-Ag and cT-Ag. The expression of Tn-Ag was then examined with the use of VVA. Of 38 cases expressing the phenotypes T-Ag(-) and cT-Ag(+), 6 had tumors that carried Tn-Ag; 5 of them suffered from invasive recurrence. These results indicated that the detection of Tn-Ag with the use of VVA in combination with the examination of T-Ag and cT-Ag is useful for estimating the degree of malignancy of bladder cancer and the patient's clinical course.

Antigens, Neoplasm↗
PubMed1987

Dissociation between serine proteinases and proline related enzymes in spleen of MRL mouse as a model of systemic lupus erythematodes.

We investigated the changes in the activities of proteases and other hydrolytic enzymes in spleens of MRL mice as a model of systemic lupus erythematodes (SLE). Although there are various abnormalities in the activities of proteases in the spleens of such animals, a multivariate study helped to extract two important components. The first component, representing the activities of serine proteinases, tended to decrease with advancing age in MRL mice but not in control animals. The second component, representing Pro-IP and prolyl endopeptidase, tended to decrease with advancing age in control animals, but not in the MRL mice. The discrepancy between these two components may be related to the immunopathologic disturbances in this model.

Animals↗
PubMed1987

Site and mechanism of growth inhibition by prostaglandins. III. Distribution and binding of prostaglandin A2 and delta 12-prostaglandin J2 in nuclei.

Cyclopentenone prostaglandins (PGs) such as PGA2 and delta 12-PGJ2 (9-deoxy-delta 9,12-PGD2) are taken up by cultured cells and exert growth inhibition. Within cells they are transferred to and accumulate in nuclei by a temperature-dependent process. In this study, the authors analyzed and compared subnuclear distribution and binding of these PGs. Nuclei accumulating either [3H]PGA2 or [3H] delta 12-PGJ2 were extracted successively with a hypotonic solution and with a 1% Triton X-100 solution, and the radioactivities in the two extracts (fractions of nucleoplasm and nuclear membrane, respectively) and the remaining residues (a fraction of chromatin and nuclear matrix) were determined. About three-fourths of PGA2-derived nuclear radioactivity was found in the extracts, and only 20% in the residues. Most of the radioactivity in the extracts was recovered in ethyl acetate under acidic conditions and identified as intact PGA2, suggesting that the majority of PGA2 in nuclei was present as free molecules. On the other hand, more than 70% of delta 12-PGJ2-derived nuclear radioactivity was associated with the residues and resistant to extraction with acidic ethyl acetate. This radioactivity, however, became extractable after brief alkali treatment and was identified as intact delta 12-PGJ2. In order to identify nuclear component binding of this PG, the authors digested the residues with either DNases or proteases. The radioactivity in the residues was almost completely released by digestion with proteases and clearly separated from DNA by ethanol precipitation. These results suggested that most of nuclear delta 12-PGJ2 bound covalently to protein(s) of chromatin and nuclear matrix.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Aspergillosis in acute hepatic failure.

Six (16.7%) out of 36 acute hepatic failure patients were associated with aspergillus infection mainly in the lungs (4 pneumonia and 2 fungus balls), which might be the cause of death in 4 cases. Preventive and therapeutic approaches following the early diagnosis have not been performed in all the cases. Fungal infection in hepatic failure should be considered to a greater extent to achieve a higher survival rate in this disease.

Acute Disease↗
PubMed1987

Decreased activities of serine proteinases in spleen of various murine models of systemic lupus erythematodes.

Previous studies indicated a relationship between immune deficiencies and abnormalities in the activities of various hydrolytic enzymes, including proteinases, in tissues. In the present study, we compared such activities in spleen among the three types of murine models of systemic lupus erythematodes (SLE) (i.e., New Zealand black/white mouse, MRL mouse, and BXSB mouse) and their controls. According to the results of multivariate analysis, it was shown that the most important enzymatic changes differentiating the pathologic animals from their controls were decreases in the activities of serine proteinases. Judging from the behavior of these enzymes in various immunological disturbances, it is likely that they play some important roles in pathophysiology of SLE.

Animals↗
PubMed1987

Studies on the mechanisms of the development of lupus nephritis in BXSB mice. I. Analyses of immunological abnormalities at the onset period.

Immunological abnormalities observed in male BXSB mice at the onset of lupus nephritis were examined. For this purpose, 60 male and 28 female BXSB mice were examined at the age of 13 weeks. Male mice showed higher values in all the parameters tested, though big variation was observed in each parameter. Correlation studies among each parameter in male mice showed that degree of the deposition of IC in the glomeruli was very closely associated with the level of circulating immune complexes (IC) and also the number of IgG-producing cells (IgGPC) but not with that of IgMPC. No significant correlation was observed between the level of IgG anti-DNA antibodies and that of IC, nor the number of IgGPC. These results convincingly indicate the relevance of enhanced IgG production in the pathogenesis of lupus nephritis.

Animals↗
PubMed1987

Differential effects of hypoxia on the turnover of norepinephrine and epinephrine in the heart, adrenal gland, submaxillary gland and stomach.

The authors examined the effects of hypoxia (8% O2 in N2) on the turnover rates of norepinephrine (NE) and epinephrine (E) in the heart, adrenal gland, submaxillary gland and stomach. The turnover rates were estimated by measuring the decrease in the content of NE and E after an i.p. injection of alpha-methyl-p-tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. After a 4-h exposure to hypoxia, the turnover rate of NE in the heart and those of NE and E in the adrenal gland were increased, whereas that of NE in the submaxillary gland was decreased. The turnover rate of NE in the stomach was unchanged. Pretreatment with hexamethonium, a ganglionic nicotinic receptor blocker, abolished the hypoxia-induced changes in the turnover rate of NE or E in the heart, adrenal gland and submaxillary gland. Furthermore, transection of the spinal cord at the level of C5-6 abolished hypoxia-induced alterations in the turnover rate of NE and E in the adrenal gland and submaxillary gland. In contrast, the hypoxia-induced changes seen in the heart persisted, although at a lower level, even after transection. These results show that the effects of hypoxia on the activities of the sympathoadrenal system differ depending on the organs; activities are increased in the heart and adrenal gland, decreased in the submaxillary gland and unchanged in the stomach. Furthermore, the present data suggest that hypoxia-induced alterations in the activities of cardiac sympathetic nerves originate in both the brain and spinal cord, including preganglionic neurons, whereas changes in the activities of the sympathetic nerves to the adrenal gland and submaxillary gland originate mainly in the brain.

Adrenal Glands↗
PubMed1987

Impairment of the extraneuronal O-methylating system of isoproterenol by stop-flow ischemia in the perfused rat heart.

Effects of ischemia on the extraneuronal O-methylating system were investigated in the perfused rat heart. Ischemia was produced by stopping of the perfusion for 30 min. Isoproterenol (ISO) was used as a model substrate for the extraneuronal uptake of catecholamines. The accumulation of ISO when catechol-O-methyltransferase (COMT) (EC 2.1.1.6) was inhibited by 3',4'-dihydroxy-2-methylpropiophenone (U-0521) was decreased by ischemia to about 50% of the control value. Ischemia decreased the formation of 3-O-methyl-ISO, a major metabolite of ISO formed by COMT, to about 30% of that in the control hearts. The efflux of extraneuronally accumulated ISO in the heart with and without ischemia was measured. The diffusion constant calculated by the slope of the efflux rate of ISO or by the efflux rate divided by the amount of ISO remaining in the heart after ischemia was about 50% of the control. The experiments showed that ischemia suppressed the extraneuronal O-methylating system (extraneuronal uptake, COMT and diffusional flux) in the rat heart. Such suppression may lead to higher concentrations of local catecholamines in myocardial infarction.

Animals↗
PubMed1986

Stimulatory effect of calmodulin antagonists on phospholipid base-exchange reactions in rabbit platelet membranes.

The properties of Ca2+-dependent incorporation of [3H]serine, [3H]ethanolamine and [3H]choline into the corresponding phospholipids mediated by base-exchange enzymes in rabbit platelet membranes were studied in the presence or absence of the calmodulin antagonists chlorpromazine, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), all of which markedly activate three base-exchange reactions. The base-exchange activities were dependent on Ca2+ both in the presence and absence of the drugs. Other metal ions tested did not stimulate the base-exchange reactions, even in the presence of the drugs. Apparent Km values for serine, ethanolamine and choline were not affected significantly by the concentration of Ca2+, with or without the drugs. [3H]Serine incorporation into phospholipid was competitively inhibited by ethanolamine and choline, [3H]choline incorporation was competitively inhibited by serine and ethanolamine, whereas [3H]ethanolamine incorporation was competitively inhibited by serine and noncompetitively by choline. These competitive and noncompetitive relations between each base were also not affected by the drugs. The amount of 45Ca2+ binding to platelet membranes was decreased by the drugs dose dependently. A weaker calmodulin antagonist, N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), only slightly stimulated the base-exchange reactions, but did clearly inhibit 45Ca2+ binding to the membranes, in the same manner as that of the other calmodulin antagonists used. The concentration of chlorpromazine, trifluoperazine, W-7 and W-5, required to produce half-maximal inhibition of Ca2+ binding, was approximately 30 microM. These results suggest that the calmodulin antagonists used activate the base-exchange reactions only in the presence of Ca2+ without changing the affinity of each free base to base-exchange enzymes. The activation of the base-exchange reactions was not due to the increase in free Ca2+ caused by the drug-induced inhibition of Ca2+ binding to platelet membranes.

Animals↗
PubMed1986

Metabolic dehydration of prostaglandin E2 and cellular uptake of the dehydration product: correlation with prostaglandin E2-induced growth inhibition.

When L-1210 murine leukemia cells were incubated with 60 microM PGE2 in culture medium containing fetal calf serum for various time, cell proliferation was inhibited dependent on incubation time. However, when the medium containing PGE2 was changed every 6 h during 24 h exposure to cells, growth inhibition became much weaker. Moreover, when the medium containing PGE2 was aged by preincubating without cells at 37 degrees C, growth inhibitory effect of the medium was enhanced with preincubation time, suggesting that active growth inhibitory compound(s) accumulated during preincubation. In culture medium containing fetal calf serum, PGE2 degraded time-dependently and the major product was identified as PGA2 by HPLC. Furthermore, when cells were incubated with the medium containing 60 microM[3H]PGE2 or the same medium aged by preincubation, we observed that the radioactivity was taken up by the cells time-dependently, and identified the incorporated radioactivity as PGA2. This uptake was closely correlated with decrease in viable cell number during incubation. These results suggested that growth inhibitory effect of PGE2 was due to the metabolic dehydration of PGE2 to PGA2, and PGA2, after taken up by cells, exerted cell growth inhibition.

Animals↗
PubMed1986

Bay K 8644, a voltage-sensitive calcium channel agonist, facilitates secretion of atrial natriuretic polypeptide from isolated perfused rat hearts.

Effects of Bay K 8644, a voltage-sensitive calcium channel agonist, on atrial natriuretic polypeptide (ANP) secretion from isolated rat hearts perfused with Krebs-Henseleit solution were investigated. After a ninety-min period for stabilization, coronary sinus effluents were collected every two min and ANP levels were measured by radioimmunoassay. The basal secretory rate of ANP was 1.65 +/- 0.15 ng/min (mean +/- standard error). Bay K 8644 stimulated ANP secretion dose-dependently. This stimulatory action was blocked by simultaneous administration of nifedipine, its competitive antagonist. Heart rate was also increased by Bay K 8644 administration. In the gel filtration study, the major secretory form of ANP corresponded to alpha-rat ANP, a 28-amino acid peptide. These results suggest that voltage-sensitive calcium channels are involved in two principal biological properties, contraction and ANP secretion, of atrial cardiocytes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Effects of morphine on hexamethonium-sensitive and -resistant excitatory responses of stomach to stimulation of vagal trunk in cats.

Electrical stimulation of the vagal trunk with 10 Hz in frequency, 3 ms in duration and 15 volt in intensity for 10 s in cats produced an excitatory response of the stomach and the response was composed of two phases, an initial rapid excitation during stimulation period and the late multi-peak response after stimulation period. The initial response was inhibited by the administrations of hexamethonium (10 mg/kg, i.v.) and atropine (100 micrograms/kg, i.v.). The late response was not inhibited by hexamethonium but was inhibited by atropine (100 micrograms/kg, i.v.). The hexamethonium-sensitive initial excitation was not affected by the administration of morphine and gamma-aminobutyric acid (GABA). On the other hand, the hexamethonium-resistant late response was attenuated by the treatment with morphine (1 to 10 mg/kg, i.v.) and GABA (100 to 500 micrograms/kg, i.v.). Such inhibitory actions of morphine and GABA on the late response were antagonized by picrotoxin. From these results, it was concluded that morphine might inhibit specifically the hexamethonium-resistant late excitatory response of the stomach without affecting the hexamethonium-sensitive initial excitatory response and the inhibitory effect of morphine on the late response of stomach might be due to action of GABA released from the intramural neurons of gastric walls in cats.

Animals↗
PubMed1986

Immunohistochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis, with special reference to Ia-positive cells with dendritic morphology.

The rat central nervous system (CNS) during experimental allergic encephalomyelitis (EAE) was analyzed immunohistochemically from the preclinical to recovery stage by using monoclonal antibodies specific for rat T lymphocyte subsets and Ia antigen. Through combination of the avidin-biotin technique and carefully selected fixative, cells with dendritic morphology (DC) and infiltrating mononuclear cells were clearly and intensely demonstrated in the CNS parenchyma during EAE. In normal and complete Freund's adjuvant (CFA)-injected controls, there were no inflammatory foci. Ia (OX3)-positive parenchymal cells were not detected, whereas W3/25 stained DC that were located mainly in the white matter and W3/13 stained axons. At the preclinical stage, 11 days after CNS/CFA sensitization, a few clusters of Ia+ DC were detected in some sections of the spinal cord. The number of Ia+ DC increased as clinical signs developed (P less than 0.001). In rats with a clinical score of 1 or 2, Ia+ DC were mainly located in the perivascular region and closely associated with infiltrating T lymphocytes. However, at moribund state (score 3), Ia+ DC were evenly distributed in gray and white matter on almost all sections of the spinal cord. In recovered rats, the numbers of inflammatory foci and Ia+ DC were less than those in clinical EAE rats (P less than 0.001). Rats without clinical signs throughout the course also contained a few clusters of Ia+ DC. Double immunofluorescent staining with OX3 and anti-glial fibrillary acidic protein (GFAP) antiserum demonstrated that Ia+ DC were negative for GFAP. Their morphology and distribution were similar to those of nucleoside diphosphatase-positive cells, suggesting that Ia+ DC are microglia. In contrast to DC, no astrocytes or endothelial cells express detectable levels of Ia antigen in control and clinical EAE rats. These findings suggest that brain cells other than Ia+ DC may not be involved in the local immune interaction. Ia+ DC may play a significant role in antigen presentation in the CNS with EAE.

Animals↗
PubMed1986

Effects of antiarrhythmic drugs on the extraneuronal accumulation of isoprenaline in perfused rat hearts.

The effects of class I, II, III and IV antiarrhythmic drugs (as classified by Vaughan Williams 1974), tetrodotoxin and beta 2-adrenoceptor antagonists on the extraneuronal accumulation of isoprenaline were examined in isolated rat hearts perfused with 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l) for 30 min at a constant flow rate (6.5 ml/min) at 40 degrees C. Quinidine (class I), verapamil (IV), diltiazem (IV), dilazep (IV), nifedipine (IV), tetrodotoxin and butoxamine, at a concentration of 10 mumol/l, significantly decreased the extraneuronal accumulation of isoprenaline. The present study demonstrated that quinidine (class I) and all of the calcium channel blockers (class IV) had potent inhibitory effects on the extraneuronal accumulation of isoprenaline. The concentrations of these drugs needed for this decrease were nearly comparable to those needed to suppress isoprenaline-tropolone-induced ventricular fibrillation (Sono et al. 1985a). The antiarrhythmic effects of quinidine and calcium channel blockers in this experimental model may be partly due to a decrease in the extraneuronal accumulation of isoprenaline.

Adrenergic beta-Antagonists↗