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Biomedical subjects

S Ohta

Publications and source records attributed to S Ohta.

At least 361 records · Page 20Linked to original sources
PubMed1997

[A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy].

The premortem diagnosis of cytomegalovirus (CMV) pneumonia is usually difficult, and mortality of it is high. A case of successful treatment with ganciclovir for cytomegalovirus pneumonia after pulmonary lobectomy is reported. The patient was a 76-year-old man. Under diagnosis as lung cancer, the right lower lobectomy was performed. After operation, pneumonia occurred on the nonoperated side and in a few days reticular shadows rapidly spread to the whole lung. Although pulse steroid therapy was performed, the interstitial pneumonitis improved only a little. Then intranuclear inclusion body-bearing giant cells were found in sputum obtained by bronchoscopy. So we diagnosed the interstitial pneumonitis as CMV pneumonia and ganciclovir was administrated. CMV pneumonia had improved for two weeks and the patient has no recurrence. When interstitial pneumonitis develop in patients after operation or steroid therapy, the differential diagnosis should include the possibility of CMV pneumonia.

Aged↗
PubMed1996

Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter.

Our previous studies on the promoter function of the human C-type natriuretic peptide (CNP) gene revealed the existence of two GC-rich cis elements essential for gene transcription in rat pituitary-derived GH3 cells. To isolate transcription factors that bind to those GC-rich elements, we screened a lambda ZAP cDNA library derived from GH3 cells by Southwestern screening. Several positive clones with specific binding abilities were obtained, and one was identical as TSC-22, a speculated transcriptional modulator stimulated by transforming growth factor beta (TGF-beta) of unknown function. TSC-22 significantly enhanced CNP promoter activity in GH3 cells. We further cloned a 1.8-kb full-length human TSC-22 cDNA from a fetal kidney cDNA library by a combination of polymerase chain reaction and the rapid amplification of the cDNA ends technique. In adults, human TSC-22 mRNA was highly expressed in brain, lung and heart. TSC-22 gene expression in GH3 and human aortic endothelial cells was stimulated by cytokines including TGF-beta, in correlation with the CNP mRNA increase. These results suggest that TSC-22 is a transcriptional regulator of the CNP gene and transmits signals from cytokines, such as TGF-beta, to CNP gene expression.

Adult↗
PubMed1996

Identification of the amino acid residues responsible for cold tolerance in Flaveria brownii pyruvate,orthophosphate dikinase.

Pyruvate,orthophosphate dikinase (PPDK), an enzyme important in C4 photosynthesis, is typically a cold-sensitive enzyme. However, a cold-tolerant form of the enzyme has been isolated from the leaves of Flaveria brownii. Using an Escherichia coli expression system and the PPDK cDNAs from F. brownii (cold-tolerant), F. bidentis (cold-sensitive) and maize (intermediate cold tolerance), site-directed mutagenesis studies indicated that as few as three amino acids residues (of 880 residues) strongly influence the cold sensitivity of Flaveria PPDK. Gel filtration analysis of the PPDK expressed in E. coli showed that subunit association and cold tolerance are closely linked.

Amino Acid Sequence↗
PubMed1996

Nitric oxide synthase inhibitor reduces delayed neuronal death in gerbil hippocampal CA1 neurons after transient global ischemia without reduction of brain temperature or extracellular glutamate concentration.

We planned a study to determine whether or not the mechanism of nitric oxide (NO) neurotoxicity involves the elevation of extracellular glutamate or changes of brain temperature in the pathogenesis of delayed neuronal death of gerbil hippocampal CA1 neurons following 5-min transient forebrain ischemia. Intraventricular injection of 5 microliters of 5.0 mg/ml N omega-nitro-L-arginine (LNNA) significantly preserved neuronal density in the central part of the CA1 region examined 7 days after 5-min ischemia [188.5 +/- 8.5/mm: 90.0% of the 209.5 +/- 11.1/mm density in the sham-operated controls vs. 16.7 +/- 6.4/mm in those injected with artificial cerebrospinal fluid (CSF) only]. There was no difference between these two groups in hippocampal temperature before, during or after 5-min ischemia. The glutamate concentration ([Glu]) during 5-min ischemia measured by a microdialysis technique was similar in the two groups (peak [Glu.] = 2.76 +/- 0.62 pmol/microliters dialysate in the artificial CSF group and = 2.93 +/- 0.64 pmol/microliters dialysate in the LNNA group). It was found that the neuronal toxicity of NO does not involve hyperthermia or the increase of extracellular glutamate concentration in the hippocampal CA1 region during 5-min ischemia.

Analysis of Variance↗
PubMed1996

Comparison of results of intracoronary implantation of the Plamaz-Schatz stent with conventional balloon angioplasty in chronic total coronary arterial occlusion.

We compared angiographic and clinical outcomes after successful revascularization of chronic total coronary arterial occlusion with the placement of the Palmaz-Schatz stent (43 patients) and conventional balloon angioplasty (53 patients). After the procedure, the coronary stent led to a greater minimal lumen diameter than conventional balloon angioplasty (2.6 vs 1.7 mm, p < 0.001), resulting in a smaller residual stenosis (6.5% vs 36.7%, p < 0.001). At 6-month follow-up, there was no significant difference in late loss between the groups, resulting in a larger minimal lumen diameter at follow-up in the stent group (1.8 vs 1.1 mm, p < 0.001). The incidence of restenosis was lower in the stent group (27.9% vs 56.6%, p < 0.005). The frequency of the combination of myocardial infarction and coronary artery bypass graft surgery tended to be less in the stent group (2.3% vs 11.3%, P = 0.09). Placement of the Palmaz-Schatz stent improved left ventricular ejection fraction by 26% in patients who had reduced left ventricular function (p < 0.05), but conventional balloon angioplasty did not. Thus, placement of the Palmaz-Schatz stent provided a wider lumen than did conventional balloon angioplasty and, therefore, reduced the incidence of restenosis in chronic total coronary arterial occlusion. The lower restenosis rate of coronary stenting would be beneficial for long-term clinical outcome in patients with chronic total occlusion.

Aged↗
PubMed1996

Chronic administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine in the brain, induces parkinsonism in a primate.

1-Benzyl-1,2,3,4-tetrahydroisoquinoline hydrochloride (1Bn TIQHCl) (22 mg/kg per day) was subcutaneously injected into a monkey, Macaca fascicularis for 66 days to investigate its acute and chronic effects Parkinsonism like motor symptoms appeared, and the acute toxicity was stronger than the chronic toxicity. This result suggested that 1BnTIQ may induce parkinsonism in humans. 1BnTIQ content in various regions of the monkey brain was determine by the gas chromatography-selected ion-monitoring method, but no significant variation was found.

Animals↗
PubMed1996

Induction of apoptosis in androgen-independent mouse mammary cell line by 1, 25-dihydroxyvitamin D3.

Androgen-dependent tumors eventually progress to independent tumors after androgen withdrawal. Effective treatment for hormone-independent tumors is therefore needed. Androgen-independent CS-2 cells could grow in serum-free culture whether androgen is present in the medium or not. In the present study, the mechanism of cell death in CS-2 cells was examined after 1, 25-dihydroxyvitamin D3[1, 25(OH)2D3] treatment. 1, 25(OH)2D3 has been examined as an anti-tumor agent, but its role in promoting cell death is poorly understood. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, the cells underwent apoptosis with 1, 25(OH)2D3 treatment. Northern-blot analysis was used to identify a series of genes whose expression per cell is enhanced during the apoptotic pathway. In the apoptotic process induced by 1, 25(OH)2D3, mRNA expression of testosterone-repressed prostatic message 2, transforming growth factor beta1, glucose-regulated 78-kDa protein and calmodulin increased. Flow-cytometric analysis showed that 1, 25(OH)2D3 treatment resulted in a block in G0/G1 of the cell cycle. These results demonstrate that androgen-independent CS-2 cells retain the ability to undergo apoptosis by 1, 25(OH)2D3. This system appears to be a good model for investigating apoptosis of hormone-independent cancer.

Actins↗
PubMed1996

Reversal of adriamycin resistance with chimeric anti-ganglioside GM2 antibody.

Ganglioside GM2 is one of the major cell-surface gangliosides expressed in human tumors. We earlier established a mouse/human IgG1 chimeric anti-GM2 antibody, KM966, which displayed anti-tumor activity in human tumor cells both in vitro and in vivo. In this study, we have screened for changes in ganglioside expressions in several drug-resistant human cancer cell lines to examine the modulation of drug resistance by immunotherapy with anti-ganglioside antibodies. Increased GM2 expression, detected by flow cytometry and thin-layer chromatography, was observed in the SBC-3/ADM and AdrR MCF7 adriamycin-resistant cell lines, in contrast with their parental lines. In other related gangliosides, ganglioside GD2 levels in AdrR MCF7 were higher than those in MCF7 cells. We confirmed increased N-acetylgalactosaminyltransferase mRNA in adriamycin-resistant cell lines, as compared with the parental cells, by Northern-blot analysis. Moreover, to investigate the possibility of exploiting the anti-tumor activity of KM966 in order to overcome resistance to adriamycin, we investigated the antibody-dependent cell-mediated cytotoxity of human peripheral mononuclear blood cells and the complement-dependent cytotoxity of human serum with KM966 against SBC-3, SBC-3/ADM, MCF7 and AdrR MCF7. Significantly higher killing via KM966 was observed in SBC-3/ADM and AdrR MCF7 cells as compared with the parental cells. This suggests that passive immunotherapy using KM966 against human adriamycin-resistant cancer may be useful for overcoming resistance to adriamycin.

Antibiotics, Antineoplastic↗
PubMed1996

Effects of new endogenous nonprotein amino acids, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives, on behavior of mice.

Several 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids were synthesized and found to have a transiently increasing effect on the locomotor activity of mice after peripheral injection. Three of the active compounds were detected in the brain after intraperitoneal administration. Two of them, the 7-hydroxy and 7-hydroxy-6-methoxy derivatives, were found as endogenous compounds in untreated rat brain and may play a physiological role. The effects of some of these compounds on the level of various endogenous amines, amino acids and metabolites were examined.

Amino Acids↗
PubMed1996

Structural characterization of a novel glycoinositolphospholipid from the parasitic nematode, Ascaris suum.

A novel glycosphingolipid containing inositol phosphate as an acidic group has been demonstrated in whole tissues of the porcine roundworm, Ascaris suum. The thin layer chromatographic pattern of the total acidic glycolipid revealed the presence of several components, of which a major component (named AGL) with positive reactions toward both orcinol-sulfuric acid (sugar) and molybdate (phosphate) spray reagents was isolated and purified by the use of successive column chromatography on DEAE-Sephadex and silicic acid (latrobeads). From structural studies including compositional sugar analysis, hydrogen fluoride degradation, methylation analysis, periodate oxidation, proton magnetic resonance spectroscopy and fast atom bombardment mass spectrometry, the structure of AGL was deduced to be Gal alpha 1-2Ins(1-->)-P-Cer. Aliphatic constituents were lignoceric acid and its 2-hydroxy homologue as the principal fatty acids, and octadecasphinganine and branched heptadecasphinganine as the major sphingoids.

Animals↗
PubMed1996

Histamine enhanced the TNF-alpha-induced expression of E-selectin and ICAM-1 on vascular endothelial cells.

Cell adhesion molecules are expressed on endothelial cells by various proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha) induces the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC). Although histamine is a potent vasoactive mediator, it does not induce the expression of E-selectin and ICAM-1. In this report, we show that histamine concentration-dependently enhances the TNF-alpha-induced expression of E-selectin and ICAM-1 on HUVEC. The histamine-enhanced expression of E-selectin and ICAM-1 was inhibited by the histamine H1 receptor antagonists, mepyramine and diphenhydramine. KW-4679 and ketotifen, antiallergic drugs with histamine H1 receptor antagonistic activity, potently inhibit the expression of E-selectin and ICAM-1. A histamine H2 receptor antagonist, ranitidine, did not affect the histamine-induced expression of cell adhesion molecules. These data indicate that histamine induces the expression of E-selectin and ICAM-1 synergistically with TNF-alpha through histamine H1 receptors.

Animals↗
PubMed1996

An additional form of rat Bcl-x, Bcl-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells.

The bcl-2 oncogene product delays apoptotic cell death and prolongs the cell survival. We cloned two bcl-2-related cDNAs from a rat thymus cDNA library by low stringency hybridization with a rat bcl-2 fragment as a probe. One of these, designated bcl-xalpha, was a counterpart of the human bcl-xL reported previously as a bcl-2-related gene (Boise, L. H., Gonzalez-Garcia, M., Postema, C. E. , Ding, L., Lindsten, T., Turka, L. A., Mao, M., Nunez, G., and Thompson, C. B. (1993) Cell 74, 597-608). The other, designated bcl-xbeta, was novel and found to be generated by an unspliced mRNA, whereas bcl-xalpha was generated from a spliced transcript. The splice junction exactly corresponded to that found in the bcl-2 gene. bcl-xbeta was specifically expressed in cerebellum, heart, and thymus. When bcl-xbeta directed by a strong promoter was introduced into an interleukin-3-dependent promyeloid cell line, FDC-P1, DNA fragmentation was observed even in the growing state in the presence of interleukin-3 although not in the control transfectants. This finding suggests that the rat bcl-xbeta gene product promotes apoptosis in the promyeloid cells.

Animals↗
PubMed1996

Immunochemical and immunohistochemical localization of Bcl-x protein in the rat central nervous system.

To explore the role of bcl-x in the regulation of cell death in the nervous system, we produced monoclonal antibodies against rat Bcl-xL protein, the major product of the rat bcl-x gene that inhibits apoptosis, and defined its distribution in rat neural tissues by immunochemical and immunohistochemical means. Western blotting of tissue homogenates identified the Bcl-x protein as two bands with molecular weights of about 29 and 31 kDa. The level of Bcl-x expression in the nervous system was high, being comparable to that in the hematolymphoid system, and higher in the fetal than in the adult brain. Subcellular fractionation studies localized Bcl-x to various subcellular compartments. In tissue culture, Bcl-x was produced by all the cell types examined, including neurons, astrocytes, oligodendrocytes and microglial cells. Immunohistochemistry revealed that Bcl-x immunoreactivity was more intense in the gray than in the white matter. In the fetal cerebral cortex, labeling was mostly confined to the neuronal perikarya, whereas in the more mature brain, the neuropil of the gray matter, as well as the glial cells in the white matter, was also stained.

Aging↗
PubMed1996

Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia.

Ciliary neurotrophic factor (CNTF) has been shown to exhibit potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues neuronal loss due to focal cerebral ischemia and prevents ischemia-induced disability of space navigation in rats. In the present in vivo study, we infused CNTF continuously for 4 weeks into the lateral ventricle, starting just after permanent occlusion of the left middle cerebral artery (MCA) of stroke-prone spontaneous hypertensive rats. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner in rats subjected to the Morris water maze task. Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischemic rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone. These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus.

Analysis of Variance↗
PubMed1996

High expression of Bcl-x protein in the developing human cerebellar cortex.

The gene bcl-x, which is related to a bcl-2, regulates programmed cell death. bcl-x may function in the development of the nervous system. We raised a polyclonal antibody against human Bcl-x protein, and investigated its distribution in the developing human cerebellum. Western blotting revealed that Bcl-x expression in the cerebellum is higher in the fetal, than in the postnatal period. Immunohistochemical studies of fetal brains localized intense Bcl-x immunoreactivity in the granule cell processes at 13-22 gestational weeks and in the Purkinje cell bodies at 24-38 weeks. The immunoreactivity decreased after birth, but was retained in the Purkinje cells at a low level until adulthood. These results suggested that Bcl-x expression in the cerebellum is developmentally regulated and involved specifically in the development of neuronal subpopulations.

Adult↗
PubMed1996

Origins of nitric oxide synthase-containing nerve fibers in the rat basilar artery with reference to the fine structure of the nerve fibers.

The origins of nitric oxide synthase (NOS)-containing nerve fibers in the rat basilar artery were studied by a combination of Fluoro-Gold retrograde tracing and immunohistochemistry. After application of Fluoro-Gold onto the middle part of the basilar artery, the dye accumulated in the sphenopalatine, otic, trigeminal, superior cervical, nodose ganglia and in the spinal ganglia at level C2 and C3. Nerve cells with NOS-like immunoreactivity were detected in the above ganglia, except for the superior cervical ganglion. Neurons that showed both NOS-like immunoreactivity and Fluoro-Gold fluorescence were numerous in the sphenopalatine and otic ganglia, and less numerous in the trigeminal, nodose and spinal ganglia. Under electron microscopy, a number of unmyelinated nerve terminals with neuronal NOS-like immunoreactivity was seen in proximity to smooth muscle cells in the tunica media of the basilar artery. These findings provide morphological evidence that NOS-containing nerve fibers in the rat basilar artery have multiple origins, and suggest that the control of posterior cerebral circulation by the parasympathetic and sensory ganglia are more complex than previously considered.

Animals↗
PubMed1996

A strategy for selective anti-cancer drug concentration increase in rat glioma tissue with Ca(2+)-channel blocker co-administration: calcium kinetics in intra-glioma arteriolar smooth muscle cells.

A rat glioma model was employed to estimate the Ca2+ kinetics in the tumor arteriolar smooth muscle cells. Electron microcytochemistry revealed that the density of intracellular Ca2+ deposits in the intra-tumor arteriolar smooth muscle cells was significantly greater, with slightly higher membrane Ca(2+)-adenosine triphosphatase (ATPase) activity, compared to the contralateral cerebral arterioles. Furthermore, the administration of tyrphostin, a tyrosine kinase inhibitor, specifically increased only the intra-tumor blood flow. These findings suggest that the condition of the intra-tumor arteriole alters the susceptibility to contraction by the accelerated Ca2+ influx into the cytoplasm mediated through the tyrosine kinase pathway. After the administration of diltiazem, which also has a blocking effect on the Ca(2+)-channel mediated through this pathway, the local intra-tumor blood flow showed an increase of 39% with a marked decrease of intracellular Ca2+ concentration of the arteriolar smooth muscle cells in the tumor, while the blood flow in the basal ganglia increased by only 8%. The intra-tumor concentration of Nimustine-HCl (ACNU) with co-administration of diltiazem was significantly increased compared to that without the co-administration. Co-administration of diltiazem may be a valuable strategy in chemotherapy for glioma in affording the selective increase of intra-tumor concentration of the anti-cancer drug.

Animals↗