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J Shimada

Publications and source records attributed to J Shimada.

At least 73 records · Page 4Linked to original sources
PubMed1998

Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase.

Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH 3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flattened phenotype of the nontransformed parental cells. The mechanism of detransformation induced by this agent had not been determined. Here, we demonstrate that depudecin inhibits histone deacetylase (HDAC) activity effectively both in vivo and in vitro. Depudecin induces similar morphological reversion in v-ras transformed NIH 3T3 cells as do other naturally occurring HDAC inhibitors such as trichostatin A or trapoxin. It competitively inhibits the binding of [3H]trapoxin in vitro and the nuclear binding of a trapoxin-coumarin fluorophore in vivo, suggesting that depudecin shares a nuclear binding protein and site on that protein with trapoxin. Furthermore, depudecin induces hyperacetylation of histones in a dose-dependent manner and at concentrations comparable with that required for detransformation. An in vitro histone deacetylase assay, using purified recombinant HDAC1, reveals that depudecin inhibits 50% of the enzyme activity at a concentration of 4.7 microM. These results demonstrate that depudecin is a novel HDAC inhibitor and suggest that its ability to induce morphological reversion of transformed cells is the result of its HDAC inhibitory activity.

3T3 Cells↗
PubMed1998

Limited use of cationic liposomes as tools to enhance the antiherpetic activities of oligonucleotides in vero cells infected with herpes simplex virus type 1.

We used commercially available cationic liposomes, lipofectin, DOTAP, and transfectam, to enhance the antiherpetic activities of phosphodiester oligonucleotides (D-oligos) or phosphorothioate oligonucleotides (S-oligos) targeted against immediate-early pre-mRNA4/5 of herpes simplex virus type 1 (HSV-1). With a 5-fold excess of S-oligos/D-oligos, formation of complexes with some of the S-oligos/D-oligos and the cationic liposomes could be visualized on agarose gel. A >5-fold excess of cationic liposomes enhanced the antiherpetic activities of Doligos, whereas there was not enhancement of the antiherpetic activities of S-oligos. As nuclear localization of D-oligos in the presence of cationic liposomes was not clear, we could not clarify the relation between antiherpetic activities of D-oligos and nuclear distribution of oligos. Subcellular distribution of S-oligos in the presence of lipofectin or DOTAP showed nuclear localization by confocal laser scanning microscopy. Transfectam had no effect on the nuclear distribution of S-oligos. These data showed that cationic liposomes would not be appropriate carriers to enhance the antiherpetic activities of S-oligos. Also, distribution of S-oligos into the nucleus does not necessarily enhance their biologic activity. Questions remain about the effectiveness of cationic liposomes in the enhancement of the antivirus activity of S-oligos.

Animals↗
PubMed1998

Enhancement of anti-herpetic activity of antisense phosphorothioate oligonucleotides 5' end modified with geraniol.

We have previously shown that antisense phosphorothioate oligonucleotide (SON) targeted against immediate early (IE) pre-mRNA5 of the herpes simplex virus type I (HSV-I) possessed potent anti-herpetic activities in vitro system. However, anti-herpetic activities of SON were not still efficient enough. Lipophilic compounds have been often conjugated with antisense oligonucleotide to enhance the biological activity. In this study, we selected geraniol as a lipophilic compound and newly synthesized SON bearing 5' terminal geraniol (geranyl-SON) toward IE pre-mRNA 5 of the HSV-1 to enhance the anti-herpetic activity. Geraniol is a olefinic terpene alcohol which is found in many essential oils. It possesses lipophilic characteristic. It is thought to be absorbed in tissue. Geraniol enhanced the anti-herpetic activity of SON with less cytotoxicity in a sequence specific manner. Terminal modification with geraniol did not affect binding affinity with complimentary DNA. Cytoplasm distribution of geranyl-SON was confirmed by confocal microscope. While some of the geranyl-SON was seen in the nucleus, unmodified SON had a punctate distribution in the cytoplasm with little in the nucleus. These results suggested that geranyl modification enhances anti-herpetic activity by changing the subcellular distribution of the oligonucleotides. Consequently geraniol-modifica-tion could provide new means for the efficient delivery of oligo-nucleotides.

Acyclic Monoterpenes↗
PubMed1998

[Identification of penicillin-resistant Streptococcus pneumoniae in nasopharynx of patient with acute otitis media by PCR].

Streptococcus Pneumoniae is a leading cause of acute otitis media (AOM). For most AOM caused by S. pneumoniae, penicillin is the antibiotic of choice. However, there are some recent reports of clinical resistance to penicillin by S. pneumoniae. The sequences of penicillin binding protein, pbpla, pbp2b and pbp2x, genes of penicillin-resistant S. pneumoniae (PRSP) were more highly divergent than those of penicillin-succeptible S. pneumoniae (PSSP). The polymerase chain reaction (PCR) can easily determine whether an S. pheumoniae isolate is susceptible or resistant to penicillin by amplifying the target gene by using a combination of primers. In this study, clinical isolates (n = 12) were obtained from the nasopharynx of patients with AOM. PCR was used to confirm the identification of an isolate as S. pneumoniae by amplifying the autolysin gene and to detect three PBP genes by amplifying parts of pbp1a, pbp2x and pbp2b. The resistance of S. pneumoniae to penicillin and other beta-lactams has been shown to be associated with mosaic mutations in the pbp1a, pbp2b and pbp2x genes. These findings suggest that rapid identification of PSSP and PISP/PRSP by PCR is possible and very useful for proper treatment of acute otitis media.

Acute Disease↗
PubMed1997

Fibroblast growth factor-2 expression is up-regulated after denervation in rat lung tissue.

To understand the role of fibroblast growth factor-2 (FGF-2) during the denervation-reinnervation processes which occur after lung transplantation, we studied FGF-2 gene expression in a rat lung denervation model. The temporal profile of FGF-2 mRNA in denervated rat lungs was quantitatively assessed by competitive reverse transcription polymerase chain reaction (RT-PCR) method. The level of FGF-2 mRNA was consistently higher in denervated lungs, showing a peak value on the 5th post-operative day. Immunohistochemical analysis with an anti-FGF-2 monoclonal antibody disclosed immunoreactivity in Schwann cells at the distal severed end of the nerve fascicle located at the lung hilus, 1 week post-surgery. This study indicates that FGF-2 gene expression is up-regulated following denervation and suggests possible roles of FGF-2 in the reinnervation process of lung tissue.

Animals↗
PubMed1997

Myocardial adenosine A2a receptor imaging of rabbit by PET with [11C]KF17837.

Adenosine A2a receptors are found in the endothelia, vascular smooth muscle cells and cardiac myocytes. The properties of a carbon-11 labeled A2a antagonist [11C]KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methy lxa nthine) for myocardial imaging were evaluated by dynamic PET scanning of the myocardium in rabbits. Myocardial uptake of [11C]KF17837 was clearly visualized by PET. The tracer was taken up at a high level by the myocardium immediately after the injection, and the myocardial level of radioactivity gradually decreased. On the other hand, an inactive [11C]Z-isomer of [11C]KF17837 showed a very low myocardial uptake and the myocardium was not visualized with a selective A1 antagonist [11C]KF15372. By co-injection with carrier KF17837 or a xanthine type A2a antagonist 7-chlorostyrylcaffeine (CSC), the myocardial uptake of [11C]KF17837 was completely blocked. The effect of non-xanthine A2a antagonists ZM 241,385 and SCH 58,261, which have a higher affinity than CSC, was smaller than that of the CSC. The effect of weak antagonists caffeine and alloxazine or a xanthine type A1 antagonist KF15372 on the radioactivity level was small. It is concluded that PET with [11C]KF17837 can image myocardial adenosine A2a receptors.

Animals↗
PubMed1997

Some biochemical properties of the components of Staphylococcus aureus binding to human platelets.

The binding properties of Staphylococcus aureus in relation to human platelets were investigated. Protease digestion (pronase E, proteinase K, trypsin), heat treatment (80 degrees C, 30 min), and sonication for 5 min significantly reduced the binding abilities of the staphylococcal cells to 0% (p < .01), 50 +/- 5% (p < .05), and 38 +/- 9% (p < .05), respectively, while mixed glycosidases did not. Inhibition experiments indicated that protein A and various sugars were ineffective. A binding study using biotinylated cell surface fractions extracted from the whole cells of S. aureus indicated that the proteins having apparent molecular weights of 14400 and 16500 estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis were involved in the binding between S. aureus and human platelets.

Bacterial Adhesion↗
PubMed1997

Characterization, cell uptake, and subcellular distribution of DNA complexes with lipoglutamides having tetraethylene glycol tails.

Lipoglutamides with tetraethylene glycol tails were synthesized. Physicochemical features of the DNA/lipoglutamide complexes were investigated by light scattering method, phase transition, and CD-spectrum. Aggregation of the DNA/lipoglutamide complex was significantly depressed compared with DNA complexes without ethylene glycol tails, and the solution showed no turbidity. The DNA/lipoglutamide complex showed a high resistance to nuclease, and an efficient internalization into tumor cells, compared with those of DNA alone. Furthermore, the DNA complex was found by confocal laser scanning fluorescence microscopy to distribute in the cytoplasmic region.

Biocompatible Materials↗
PubMed1997

[Causative factors resulting in intractability of congenital hydrocephalus--analysis of psychomotor development and MRI findings of the brain in sixteen congenitally hydrocephalic patients].

Sixteen patients out of 58 children with congenital hydrocephalus were retrospectively investigated in terms of their psychomotor development and morphological findings of the brain by magnetic resonance imaging (MRI), and morphological backgrounds of the brain in patients affected by "intractable hydrocephalus" were intended to be clarified. The 16 patients were primarily diagnosed as having aqueductal stenosis or communicating hydrocephalus during the era before introduction of MRI. On the basis of the rate of head growth, sixteen patients were divided into three groups; group-1: overt neonatal hydrocephalus (5 cases) ; group-2: rapidly progressive hydrocephalus with normal head circumference at birth (5 cases); and group-3: slowly progressive hydrocephalus with its onset after the neonatal period (6 cases). Psychomotor development of the 16 cases was analyzed by using various methods including the Tanaka-Binet intelligence test and WISC-R. Four cases in group-1 and all cases in group-2 were found to have IQ or DQ below 50, while the other remaining cases were found to have IQ of 82 in group-1 (one case) and IQ ranging from 67 to 113 in group-3. MRI performed in those 9 cases with IQ below 50 revealed various morphological abnormalities of the brain. Those abnormalities were characterized by disturbance of organogenesis and/or histogenesis of the brain dating from the first 20 weeks of fetal life. It is strongly suggested that in the pathogenesis of intractable hydrocephalus developmental malformation of the brain occurring during the first 20 weeks of gestation are involved. Functional and morphological impairments of the brain possibly caused by progression of fetal hydrocephalus and delay of CSF diversion before and after birth seem important in the pathogenesis of intractable hydrocephalus.

Adolescent↗
PubMed1997

[A case of spontaneous cervical internal carotid artery dissection].

Dissection of the extracranial carotid artery is a recognized cause of ischemia, particularly in young persons who present with acute neurologic deficits, both transient and permanent. We describe a patient with a spontaneous dissection of the cervical internal carotid artery (ICA). A previously healthy 24-year-old man was hospitalized because of a sudden onset of right hemiparesis and consciousness disturbance. In reality, right cervical pain preceded this attack. The first brain MRI revealed a cerebral infarction in the right cerebral hemisphere including basal ganglia. A conventional angiography was performed 1 week later. The following angiographic picture was considered to be consistent with the diagnosis of cervical artery dissection: gradually tapered occlusion beginning distal to the carotid bifurcation. And MRA revealed the same finding. A cervical MRI revealed as an eccentric signal void (corresponding to the residual lumen) surrounded by a semilunar hyperintensity (corresponding to the mural hematoma) on T1- and T2-weighted images. Dynamic CT scan (D-CT) revealed an eccentric and crescent contrast enhancement (corresponding to the residual lumen) surrounded by a relative hypodensity compared with muscle (corresponding to the mural hematoma), itself surrounded by a thin annular enhancement. From these results, we diagnosed this patient with ICA occlusion for dissection of the extracranial carotid artery. But we decided this case contraindication of anastomosis because he had had a major stroke. Our findings suggest that MRA, cervical MRI and DCT provide early recognition of internal carotid artery dissection and monitoring of its resolution. Thus, these studies may guide clinical decisions according to the development of the dissection.

Adult↗
PubMed1997

Experimental hematogenous osteomyelitis by Staphylococcus aureus.

To assess bone marrow lodgement of bacteria that produce osteomyelitis, 10(6) colony forming units of 16 nonhemolytic strains of Staphylococcus aureus was injected intravenously into mice. Eleven of 16 strains showed bone marrow lodgement without the death of mice. The M-138 strain induced osteomyelitis in 100% of the mice. Furthermore, the difference of compact colony forming active substance activity between bone marrow lodgement and nonlodgement strains was statistically significant. Compact colony forming active substance, which is an alkali stable polysaccharide located on the cell surface of Staphylococcus aureus strain, caused compact formation of the strains in serum soft agar or fibrinogen soft agar, and it clotted animal plasma. These results suggest that bacterial factors are important for bacterial lodgement at the onset of staphylococcal hematogenous osteomyelitis.

Animals↗
PubMed1997

Pathogenesis of reduced egg production and soft-shelled eggs in laying hens associated with Leucocytozoon caulleryi infection.

The pathogenesis of reduced egg production with soft-shelled eggs in laying hens naturally infected with Leucocytozoon caulleryi was investigated. Many large schizonts of L. caulleryi schizonts were seen in the ovary and oviducts of chickens. Granulomatous and lymphocytic inflammation, edema, and pressure atrophy were associated with these schizonts. The uterine region that secretes the egg shell exhibited the most severe damage. These lesions in the reproductive organs may explain the mechanism for causing the reduced egg production and soft-shelled eggs in laying hens infected with L. caulleryi.

Animals↗