Search PubMed⌕ Search

Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 325 records · Page 18Linked to original sources

Monocyte-vascular smooth muscle cell interaction enhances nitric oxide production.

OBJECTIVE: The adhesive interaction of monocytes and vascular smooth muscle cells (VSMCs) has been suggested to be a regulatory signal in the cellular activation that is involved in the pathogenesis of atherosclerosis. We investigated the effects of monocyte-VSMC interaction on inducible nitric oxide (NO) synthase expression. METHODS: NO production by the cultured cells was determined by measuring the nitrite content of the culture media using the Griess reagent. The expression of inducible NO synthase protein was assayed by Western blotting. RESULTS: Interleukin-1 beta (IL-1 beta) induced nitrite production by VSMCs in a time-dependent manner. The addition of the mouse monocyte cell line J774 to IL-1 beta-stimulated VSMCs further increased nitrite production in a monocyte number-dependent manner. Enhanced nitrite production by coculture was accompanied by increased inducible NO synthase protein accumulation. Addition of tumor necrosis factor-alpha (TNF-alpha) also enhanced IL-1 beta-induced nitrite production by VSMCs, but TNF-alpha showed no effect in the presence of monocytes. Coculture of monocytes and VSMCs in the presence of IL-1 beta secreted substantial amounts of TNF-alpha. The production of nitrite by coculture was markedly inhibited by an anti-TNF-alpha antibody. CONCLUSIONS: The present study revealed that direct cell-to-cell interaction between monocytes and VSMCs enhances NO production, suggesting an important role for their interaction in the pathogenesis of atherosclerosis.

Animals↗

Effects of vesnarinone on nitric oxide synthesis in rat cardiac myocytes.

OBJECTIVE: The purpose of this study was to investigate the effects of vesnarinone on nitric oxide (NO) synthesis in cardiac myocytes. METHODS: We measured the accumulation of nitrite, a stable oxidation product of NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. RESULTS: Incubation of the cultures with interleukin-1 beta (IL-1 beta; 10 ng/ml) and tumor necrosis factor alpha (TNF alpha; 10 ng/ml) caused a marked increase in nitrite production. Although vesnarinone by itself showed no effect on nitrite accumulation, it enhanced cytokine-induced nitrite production by cardiac myocytes in a dose-dependent manner. The effect of vesnarinone was completely abolished in the presence of NG-monomethyl-L-arginine or actinomycin D. The vesnarinone-induced nitrite production was accompanied by increased iNOS protein expression. In the presence of dibutyryl-cAMP, cytokine-induced nitrite accumulation was further increased, but the stimulatory effect on vesnarinone on nitrite accumulation was diminished. The effect of vesnarinone was also inhibited by Rp-8-Br-cAMPS, a competitive inhibitor of protein kinase A, in a dose-dependent manner. CONCLUSIONS: These findings indicate that vesnarinone increases NO synthesis in cytokine-stimulated cardiac myocytes, at least partially through a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗

Effect of anti-IL-4 and anti-IL-5 antibodies on allergic airway hyperresponsiveness in mice.

In order to study the role of IL-4 and IL-5 in allergen-induced airway hyperresponsiveness in mice, the effect of the combined administration of anti-IL-4 and anti-IL-5 monoclonal antibodies (mAbs) on IgE response, airway inflammation and airway hyperresponsiveness was studied in sensitized Balb/c mice. Three inhalations of antigen caused an increase in the number of eosinophils in bronchoalveolar lavage fluid and in airway responsiveness to acetylcholine, with a significant elevation in the serum antigen-specific IgE level. Anti-IL-4 mAb inhibited IgE production but did not affect airway eosinophilia or hyperresponsiveness. Moreover, anti-IL-5 mAb inhibited airway eosinophilia but did not affect IgE production or airway hyperresponsiveness. The combined administration of anti-IL4 and anti-IL-5 mAbs, however, inhibited IgE antibody production, airway eosinophilia and hyperresponsiveness. These results suggest that inhibitory action of IL-4 and IL-5 in combination can effectively suppress the onset of antigen-induced airway hyperresponsiveness in mice.

Administration, Inhalation↗

Treatment of acute superior sagittal sinus thrombosis by t-PA infusion via venography--direct thrombolytic therapy in the acute phase.

BACKGROUND: Dural sinus thrombosis is a relatively rare syndrome, often with a very poor prognosis. Systemic anticoagulant therapy has produced poor results; therefore rapid recanalization of the affected vessels is essential. The recent advancements in angiographic technique and catheter technology enable us to perform direct selective venography. CASE REPORT: We observed a case of acute superior sagittal sinus thrombosis in a pregnant woman. The patient's consciousness level and motor function gradually deteriorated. Direct thrombolysis was performed via venography. RESULTS: The patient was treated successfully by thrombolysis with infusion of t-PA via selective venography within 2 days of rapid clinical deterioration and sustained a dramatic improvement of her neurological deficits. CONCLUSIONS: Direct thrombolysis via selective venography is considered a safe and useful treatment for dural sinus thrombosis in the acute phase.

Acute Disease↗

Decondensation of the mouse sperm nucleus within the interphase nucleus.

Sperm nuclei incorporated into the cytoplasm (ooplasm) of fertilised mouse eggs at the pronuclear stage remain condensed, whereas those injected into male or female pronuclei decondense. Similarly, sperm nuclei injected into germinal vesicles of immature oocytes or the nuclei of 2-cell embryos decondense, while those entering the cytoplasm of these oocytes/embryos do not. These facts seem to suggest that factors necessary for the decondensation of sperm nucleus are present in interphase nuclei and are released into the ooplasm during nuclear envelope breakdown. Nucleoplasmin, which is synthesised in the cytoplasm and accumulated within the nucleus, is likely a major candidate for these factors.

Animals↗

Cloning of tropomyosins from lobster (Homarus americanus) striated muscles: fast and slow isoforms may be generated from the same transcript.

Complementary DNAs encoding fibre-type-specific isoforms of tropomyosin (Tm) have been isolated from lobster (Homarus americanus) striated muscle expression libraries made from poly(A)+ RNA purified from deep abdominal (fast-type) and crusher-claw closer (slow-type) muscles. A cDNA of slow-muscle Tm (sTm1), containing a complete open reading frame (ORF) and portions of the 5' and 3' untranslated regions (UTRs), encodes a protein of 284 amino acid residues with a predicted mass of 32,950, assuming acetylation of the amino terminus. The nucleotide sequence of a fast-muscle tropomyosin (fTm cDNA), which includes the entire ORF and part of the 3' UTR, is identical to that of sTm1 cDNA, except in the region encoding amino acid residues 39-80 (equivalent to exon 2 of mammalian and Drosophila muscle tropomyosin genes). The deduced amino acid sequences, which display the heptameric repeats of nonpolar and charged amino acids characteristic of alpha-helical coiled-coils, are highly homologous to tropomyosins from rabbit, Drosophila, and shrimp (57% to 99% identities, depending on species). Northern blot analysis showed that two transcripts (1.1 and 2.1 kb) are present in both fibre types. Mass spectrometry indicated that fast muscle contains one major isoform (fTm: 32,903), while slow muscle contains two major isoforms (sTm1 and sTm2: 32,950 and 32,884 respectively). Both Tm preparations contained minor species with a mass of about 32,830. Sequences of peptides derived from purified slow and fast Tms were identical to the deduced amino acid sequences of the sTm1 and fTm cDNAs, respectively, except in the C-terminal region of fTm. The difference in mass between that predicted by the deduced sequence (32,880) and that measured by mass spectrometry (32,903) suggests that fTm is posttranslationally modified, in addition to acetylation of the N-terminal methionine. These data are consistent with the hypothesis that the fTm and sTm1 are generated by alternative splicing of two mutually-exclusive exons near the 5' end of the same gene.

Abdominal Muscles↗

Angiotensin-Converting Enzyme Gene Polymorphism and Plasminogen Activator Inhibitor 1 Levels in Subjects with Cerebral Infarction.

It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to cerebral infarction is still controversial. Plasminogen activator inhibitor 1 (PAI-1) is also a predictor of risk of atherothrombotic disease. In this study we investigated the association of the ACE gene polymorphism and plasma PAI-1 levels in subjects with cerebral infarction. We evaluated the genotype of the ACE gene in 26 subjects with and 28 subjects without a history of ischemic stroke. The ACE genotype was analyzed by the polymerase chain reaction. Plasma PAI-1 antigen levels were measured by ELISA. There were no differences in accepted risk factors between the groups with or without cerebral infarction. However, the frequency of the D allele was significantly higher in subjects with cerebral infarction (0.63) than in those without infarction (0.39) (chi(2) = 6.306, P = 0.012). The frequency of the DD genotype of the ACE gene was also significantly higher in subjects with than in those without cerebral infarction (DD: 46.2%, ID: 34.6%, II: 19.2% vs. DD: 14.3%, ID: 50.0%, II: 35.7%, chi(2) = 6.689, P = 0.035). Plasma PAI-1 levels were not significantly different between groups with and without cerebral infarction. There was no association between the ACE genotype and PAI-1 levels. The DD genotype of the ACE gene is associated with cerebral infarction, which is independent of plasma PAI-1 level.

Journal Article↗

Donor lymphocyte transfusion for the treatment of Epstein-Barr virus-associated lymphoproliferative disorder of the brain.

EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. A 31-year-old Japanese woman in the second chronic phase of CML received an allogeneic BMT from her HLA 2-locus-incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two courses of donor lymphocyte transfusions (DLT) of 10(6)CD3+ T cells/kg of body weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient died of recurrent blastic crisis of CML. This case suggests that DLT may be ineffective for the treatment of CNS EBV-LPD.

Adult↗

Overexpression of CAF1 encoding a novel Ca2+-binding protein stimulates the transition of Dictyostelium cells from growth to differentiation.

Among the expressed genes associated with the switch-over of Dictyostelium cells from cell proliferation to differentiation, the Calfumirin-1 (CAF1) gene has been shown to be preferentially expressed at the initial step of differentiation, encoding a novel Ca2+-binding protein (Abe & Maeda 1995). To analyze precisely the function of CAF1, transformants overexpressing the CAF1 mRNA at the vegetative growth phase and also CAF1-null mutants were prepared, and their developmental features were compared with those of parental wild-type cells. As a result, the CAF1-overexpression was found to promote cell differentiation, possibly through prompt induction of the cAMP receptor 1 (CAR1) gene expression. In addition, the CAF1-overexpressing cells were able to differentiate even under low external Ca2+ ([Ca2+]e) conditions around 10(-6) mol/L at which non-transformed wild-type cells never differentiated. Unexpectedly, however, the CAF1-null mutant produced by homologous recombination exhibited apparently normal development to form fruiting bodies on non-nutrient agar. These results seem to indicate that CAF1-overexpression has a stimulatory effect on differentiation, but that the CAF1 protein is not necessarily required for the phase-shift of cells from growth to differentiation.

Animals↗

Rapid patterning of Dictyostelium discoideum cells under confined geometry and its relation to differentiation.

The following was recently reported by Bonner et al. (1995): (1) Rapid differentiation occurred into two zones in Dictyostelium discoideum cells confined in a fine glass capillary. The cells in the anterior zone exposed to the air appear similar to prestalk cells, while the posterior zone isolated from the air mimics prespore cells. (2) The volumes of the two zones are proportional to each other for different sized cell masses, and the proportion is the same as that in normal migrating slugs. We investigated the nature of this newly discovered rapid differentiation in a slightly modified geometry. Exponentially growing cells were harvested, washed to remove external nutrients, and pelleted by centrifugation. Subsequently, a small drop of the pelleted (starved) cells was placed on a slide glass and then confined in a two-dimensional space between the slide glass and a coverslip, with help of spacers whose thickness varied from 25 to 100 microm. As a result, a dark zone, which looked optically different, emerged within several minutes in the periphery of the disc of the confined cells, corresponding to the zonation in a capillary as previously reported. When the width of the peripheral zone was measured for more than 30 samples of different diameters for each thickness of the spacers, the width was found to be always about 100 microm, irrespective of the size difference of the cell mass placed. This seems to be contradictory to the previous observation made by Bonner et al. (1995). We also examined oxygen concentration dependence on the zone width. The zone width was found to be independent of the oxygen concentration at low concentrations, but increased rapidly at high concentrations. A reaction-diffusion mechanism for formation of the zone and possible involvement of atmospheric oxygen (O2) in the initial steps of cell differentiation and pattern formation is discussed.

Animals↗

Induction of 72-kDa inducible heat shock protein (HSP72) in cultured rat astrocytes after energy depletion.

Protein synthesis is important in the readaptive processes for cultured astrocytes after hypoxia and subsequent reoxygenation. We have identified 72-kDa inducible heat shock protein (HSP72) as a major stress protein in reoxygenated astrocytes. To assess the mechanism for reoxygenation-mediated induction of HSP72, a reporter gene that consists of a human HSP promoter fused to the luciferase gene was transfected into cultured astrocytes. Analysis of cellular energy nucleotides showed an increase of the ADP/ATP ratio after reoxygenation, which synchronized with activation of the HSP promoter. Activation of the HSP promoter was also observed after an addition of iodoacetic acid to hypoxic astrocytes, which reached the maximum when the ADP/ATP ratio reached 50%, but further decline in the energy profile caused inactivation of this promoter. Inhibition of protein synthesis after reoxygenation resulted in temporary restoration of the energy profile and suppression of the DNA binding activity of the heat shock factor. Addition of quercetin greatly decreased the [3H]leucine incorporation in the polysome fraction without any effect on the mature mRNA formation. These data suggest that the energy depletion in reoxygenation triggers induction of HSP72 after reoxygenation, which may act as a pivotal mediator in the stress response of reoxygenated astrocytes by facilitating protein synthesis.

Adenine Nucleotides↗

Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance.

Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. In the absence of drugs, the replication rate of all infectious clones generated was comparable to that of wild type HIV-1. However, in the presence of zidovudine or didanosine, the comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151) > HIV-1(75/77/116/151) approximately HIV-1(151), whereas that for drug resistance was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) > or = HIV-1(77/116/151) > HIV-1(151). The virologic features of these infectious mutants suggest that HIV-1 develops drug resistance through one or more mutations, which, however, sacrifice replicative capability; then it finally acquires optimal replication competence by additional mutations when the multi-dideoxynucleoside-resistant mutant emerges.

Animals↗

Chronic effects of a novel, orally active endothelin receptor antagonist, T-0201, in dogs with congestive heart failure.

Endothelin (ET)-1 increases in plasma during congestive heart failure (CHF). Some ET antagonists improve hemodynamics, suggesting its potential benefits in the treatment of CHF. We examined the acute and chronic effects of a new ET receptor antagonist, T-0201 (Tanabe Seiyaku Co. Ltd., Japan), in CHF. To confirm the in vivo effects of T-0201, we observed the inhibitory effects of T-0201 (1-100 micrograms/kg) on the response of blood pressure to exogenously administered ET-1 (0.75 nmol/kg) in conscious normal dogs. Pretreatment with T-0201 significantly inhibited the ET-1-induced initial hypotension that is mediated by ETB receptors, and attenuated the subsequent hypertension, which is primarily mediated by ETA receptors. Thus, T-0201 at a dose of 100 micrograms/kg not only works as a potent ETA antagonist but also shows antagonist activity for ETB receptors in dogs. To evaluate the chronic therapeutic effects of T-0201, we administered T-0201 (0.3 mg/kg/day; n = 5) orally to dogs with CHF induced by rapid right ventricular pacing (22 days, 270 beats/min) for 15 days, beginning 8 days after pacing. T-0201 significantly prevented the deterioration of cardiorenal function during the development of CHF, expressed as a decrease in cardiac pressure and an increase in cardiac and urine output. These results suggest that chronic antagonism of both ET receptors prevents the progressive exacerbation of CHF.

Animals↗

Assay for detecting IgE and IgG antibodies against Candida albicans cell-wall mannan.

In the present study, we assayed mannan-specific IgE and IgG antibodies in samples of serum isolated from blood collected from adult patients with bronchial asthma, using a liquid-phase method with a polysaccharide, mannan (Mn), purified from Candida albicans (C. alb), and investigated the relationships of allergenicity among a crude extract of C. alb, purified Mn, and acid protease (AP), The correlations between the titers of anti-Mn A and anti-Mn B IgE and IgG were very strong, and the levels of inhibition of anti-Mn A IgE and IgG reactions by Mn A and Mn B were almost identical. Although no common allergenicity was observed between Mn A and AP because there was no correlation between the titers of anti-Mn A and anti-AP IgE, and no inhibition of the anti-Mn A IgE reaction by AP, both antigens were found to exist in crude C. alb. The level of inhibition of anti-crude C. alb IgG reaction by Mn A or Mn B was about 60%. Approximately 70% inhibition of the anti-Mn A IgE reaction was observed for eight different fungal allergen extracts, but no inhibition was observed for 11 of the other fungal allergen extracts tested. The above results indicate that common antigenicity was observed between Mn A and Mn B in the human IgE and IgG antibody production system, and the cross-allergenicity observed among some fungi was considered to be the result of the common antigenicity of Mn isoforms.

Allergens↗

An attempt of radar chart expression of a self-rating scale for sleep disturbance.

We made an attempt to express a complaint of sleep disturbance by a self-rating scale of radar chart mode. The questionnaire for sleep disturbance is made up of eight items. Each item was scored from grade 1 to 4. The score of each item was projected to the MY radar chart, designed by us. It is noted that this method is useful in following the effect of hypnotics on sleep disturbance.

Adult↗

Ureterocolic fistula secondary to colonic diverticulitis.

We describe the case of a 45-year-old woman with a ureterocolic fistula caused by colonic diverticulitis. She had a 10-year history of intermittent left flank pain that had not been treated. The fistulous tract between the left ureter and sigmoid colon was confirmed by retrograde urography and a barium enema. A nephroureterectomy was successfully performed.

Barium Sulfate↗