Biomedical subjects

M Onishi

Publications and source records attributed to M Onishi.

At least 37 records · Page 2Linked to original sources

PubMed1998

Enhancement of human immunodeficiency virus type 1 (HIV-1) infection via increased membrane fluidity by a cationic polymer.

Cationic polymers are known to have potent activity against bacteria, but their effects on viral activity have been little studied. We investigated the effect of one such polymer, polyethyleneimine (PEI), on HIV-1 infection. Although virus-cell binding was significantly inhibited by PEI, HIV-1 infection in human T-cell lines such as MT-4 and MOLT-4 was accelerated conversely when the drug treatment was carried out, after the virus had attached to the cells or PEI was simultaneously added to the virus and cell culture system. This paradoxical effect of PEI on HIV-1 infection was examined using HIV-1 chronically infected cells (MOLT-4/HIV-1). Dissociation of the glycoprotein gp120 (as revealed by exposure of transmembrane protein gp41) from MOLT-4/HIV-1 cells and the resultant fusion of these cells was shown to be induced by the addition of PEI. Accordingly, it was suggested that the binding inhibition of HIV-1 to CD4-positive cells by PEI was due to the shedding of gp120 from HIV-1 particles, and this PEI rather promoted membrane fusion between the virus and cells leading to the enhancement of HIV-1 infection. Similarly, dissociation of gp120 from MOLT-4/HIV-1 was also induced by sCD4. The effect of these reagents on changes in membrane fluidity was evaluated by polarization (p) measurements, and it was observed that the acceleration of membrane fluidity occurred only in the PEI system. Therefore, it is likely that PEI accelerates HIV-1 infection by facilitating virus entry into the host cells through an increase in membrane fluidity.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Clinical electroencephalographic study of nine pediatric patients with convulsion induced by the TV animation, Pocket Monster.

BACKGROUND: To determine the usefulness of a few types of photic stimulation in patients with photo-convulsive response. METHODS: A clinical electroencephalographic study was conducted in nine children who developed convulsions and other symptoms while they watched the TV animation and were subsequently treated at the hospital. Photic stimulation was applied with their eyes open or closed. Another photic stimulation was applied with the video tape of the animation. RESULTS: A photoparoxysmal response (PPR) was never seen in the electroencephalographs (EEG) in any of these patients when photic stimulation was applied with their eyes closed, while PPR was seen in three of seven patients when photic stimulation was applied with their eyes open. Two patients (siblings) showed no specific abnormality when photic stimulation was applied with their eyes either open or closed. However, myoclonus and PPR appeared when the EEG was conducted while they watched the video tape of the animation under supervised conditions. CONCLUSIONS: In a society where people are exposed to abundant TV games, TV animation or videos, self-restraint or regulations of frequent use of flickering scenes is thought to be necessary. However, it is also thought to be necessary to conduct EEG by applying photic stimulation, not only with the eyes closed, but also with the eyes opened or by applying flickering red light stimulation, which is emitted from a strong light source, or a combination of two colors, such as red and blue or red and green, in patients with suspected photosensitivity.

Adolescent↗

PubMed1998

Identification and characterization of a constitutively active STAT5 mutant that promotes cell proliferation.

STAT (signal transducers and activators of transcription) proteins are transcription factors which are activated by phosphorylation on tyrosine residues upon stimulation by cytokines. Seven members of the STAT family are known, including the closely related STAT5A and STAT5B, which are activated by various cytokines. Except for prolactin-dependent beta-casein production in mammary gland cells, the biological consequences of STAT5 activation in various systems are not clear. We applied PCR-driven random mutagenesis and a retrovirus-mediated expression screening system to identify constitutively active forms of STAT5. By this strategy, we have identified a constitutively active STAT5 mutant which has two amino acid substitutions; one is located upstream of the putative DNA binding domain (H299R), and the other is located in the transactivation domain (S711F). The mutant STAT5 was constitutively phosphorylated on tyrosine residues, localized in the nucleus, and was transcriptionally active. Expression of the mutant STAT5 partially dispenses with interleukin 3 (IL-3) as a growth stimulant of IL-3-dependent cell lines. Further analyses of the mutant STAT5 have demonstrated that both of the mutations are required for nuclear localization, efficient transcriptional activation, and induction of IL-3-independent growth of an IL-3-dependent cell line, Ba/F3, and have indicated that a molecular basis for the constitutive activation is the stability of the phosphorylated form of the mutant STAT5.

Animals↗

PubMed1998

Anticoagulant and antiprotease activities of a heparinoid sulfated glucoside-bearing polymer.

We studied anticoagulant and antiprotease activities of the poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA)-sulfate] in plasma and purified enzyme systems in order to evaluate the anticoagulant behavior of a heparin-like sulfated glucoside-bearing polymer. As a result, we found that poly(GEMA)-sulfate can inhibit some coagulation proteases, although its antiprotease behavior differed from those of heparin and dextran sulfate. Poly(GEMA)-sulfate could not enhance antithrombin activity; therefore, we did not observe any significant inhibition of Factor Xa via antithrombin. However, we found that poly(GEMA)-sulfate was able to inhibit thrombin through the activation of heparin cofactor II. In addition, poly(GEMA)-sulfate was able to inhibit Tenase. In our previous research. we found that the anticoagulant activity of poly(GEMA)-sulfate is due primarily to the formation of an insoluble complex with fibrinogen. This paper showed that the antiprotease activities of poly(GEMA)-sulfate contribute to some extent to its anticoagulant activity.

Anticoagulants↗

PubMed1998

A study on the promotion and suppression of demineralization of human dental hard tissues and hydroxyapatite.

Demineralization of human dental enamel and dentine and their analogue compound, hydroxyapatite, was examined by using pH-metry to measure the time-courses of neutralization of acetate, formate, lactate or propionate buffer solution or of acidification of EDTA solution. The extent of neutralization by enamel, dentine and hydroxyapatite was different for each acid but increased in the same order: propionate, acetate, lactate and formate. This order was consistent with that of the K values of these acids. The pH-metry was used to determine the influences of sodium chloride and sucrose on demineralization of enamel, dentine and hydroxyapatite by acetate, formate, lactate and propionate and by EDTA. The demineralization by these bioorganic acids was suppressed by sucrose but promoted by sodium chloride, except that the demineralization of enamel by acetate and propionate was little affected. The demineralization of enamel, dentine and hydroxyapatite by EDTA was little affected by sucrose but promoted by sodium chloride. The promotive effect of sodium chloride on demineralization may be due to the increasing of solubility product by this salt and the suppressive effect of sucrose may be due to the formation of a calcium saccharate formed from the sucrose reacted with calcium on the surface of apatite crystal and/or the reduction of solubility product by the sucrose. In this study, it was also ascertained that the use of pH-metry made it possible to determine easily the demineralization.

Acetic Acid↗

PubMed1998

Cytokine receptors: structures and signal transduction.

The characteristic features of cytokines are functional pleiotropy and redundancy. Each cytokine is produced by a variety of cell types and acts on a wide range of target cells and tissues. Many cytokines have overlapping biological activities in the same cells. It was originally thought that each cytokine has a specific receptor and a unique signal transduction system. However, extensive studies on cytokines and their receptors revealed that many cytokines share receptor subunits and signal transduction system, and that biological functions of a single cytokine can vary depending on the status of the cells. Therefore, it is important to know the structure and function of cytokine receptors to understand the pleiotropy and redundancy as well as specificity of cytokines. Among signal transduction pathways, recently identified Jak/STAT pathway, which connects activation of the receptor complexes and transcription of various genes directly, would give us further insights in the mechanisms of cytokine action.

Animals↗

PubMed1998

[Internalized norms and social norms relating to negative health behaviors. The relationship of sociodemographic characteristics and reference groups].

So-called "negative health behaviors" (e.g. smoking, excessive eating/drinking), which are related to morbidity and mortality, are generally well known to the public. However there are many who undertake negative health behaviors despite knowing of their negative health effects. Using a mail survey of subjects aged 25 to 54, we examined reasons and justifications for engaging in negative health behaviors and their related factors from the lay person's perspective. Concerning the reasons for negative health behaviors, we hypothesized seven concepts (work priority, group harmony priority, the contribution to relaxation, tools for communication, prior orientation focused on the present, individualistic priority, and appearance), and devised multiple questions for each concept. The results are as follows. 1. Compared to females, males tended to support of the five concepts about the internalized norms concerned with negative health behaviors (e.g. the tendency of each individual to approve or disapprove of the reasons for negative health behaviors). In females, the younger generation and those that were married expressed more support than the older and the unmarried. There were differences in males according to occupation. 2. Concerning which reference groups had the largest influence on the social norms concerned with negative health behaviors (e.g. the perceptions as to what degree a group regards the reasons about negative health behaviors as desirable), most perceived that the "office" and "friends" groups would be more supportive of reasons for negative health behaviors than the "family" groups. 3. The health behaviors, which correlated with the internalized norms or the social norms concerned with negative health behaviors, were eating breakfast, smoking, and drinking (frequency and amount). In particular, drinking behavior was influenced most by the internalized norms and the social norms.

Adult↗

PubMed1996

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer.

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3-dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.

Animals↗

PubMed1996

Applications of retrovirus-mediated expression cloning.

We have recently established a novel expression cloning system using retroviral vectors. The system is based on a high-efficiency packaging cell line, BOSC23, and a simplified retroviral vector, pBabeX, carrying no selection marker. cDNA libraries, constructed in the pBabeX vector, are transiently transfected into BOSC23 cells. The supernatant contains more than 3X10(6)/mL, which would cover large complexities of cDNA libraries. The retrovirus stock gave 100% infection efficiency in NIH3T3 cells and 5-40% infection efficiency in various hematopoietic cell lines. In contrast to the conventional expression cloning system, in which it is necessary to transfect cDNA libraries transiently into particular cell types such as COS cells, retrovirus-mediated expression cloning allows us to transduce cDNAs into a wide variety of cell types. This method therefore makes it possible to select cells expressing a cDNA of interest by various functional assays. When combined with polymerase chain reaction (PCR)-driven random mutagenesis, this system is also useful in searching for mutations of various molecules that will result in alterations of their functions.

3T3 Cells↗

PubMed1996

Cytolysis of B-16 melanoma tumor cells mediated by the myeloperoxidase and lactoperoxidase systems.

Halide-dependent cytolysis of B-16 melanoma cells mediated by myeloperoxidase and lactoperoxidase systems was observed by turbidimetry. A significant decrease in turbidity, which is indicative of cytolysis, was found when a system consisting of myeloperoxidase, a source of hydrogen peroxide (glucose+glucose oxidase), and chloride or bromide were added to a B-16 melanoma cell suspension in the pH 4.7-6.0 region. The myeloperoxidase could be replaced by lactoperoxidase in the system containing bromide, but not that containing chloride. B-16 melanoma cells exposed to myeloperoxidase or lactoperoxidase systems at pH 5.5 or 7.0 were implanted by subcutaneous inoculation into C57BL/6CrSlc mice. After 14 days, a significant suppression of the growth of black tumors was detected in the groups of mice inoculated with melanoma cells exposed to the systems containing myeloperoxidase, glucose, glucose oxidase and chloride or bromide, or the system containing lactoperoxidase, glucose, glucose oxidase and bromide, at pH 5.5, but no significant suppression was observed at pH 7.0. From these findings, we concluded that the exposure of B-16 melanoma cells to a system consisting of myeloperoxidase, hydrogen peroxide (generated by the glucose+glucose oxidase system) and chloride or bromide, or of lactoperoxidase, the hydrogen peroxide and bromide, at moderately acidic pH, causes cytolysis is accompanied by cell death.

Animals↗

PubMed1995

Efficient screening of retroviral cDNA expression libraries.

Expression cloning of cDNAs was first described a decade ago and was based on transient expression of cDNA libraries in COS cells. In contrast to transient transfection of plasmids, retroviral gene transfer delivers genes stably into a wide range of target cells. We utilize a simple packaging system for production of high-titer retrovirus stock from cDNA libraries to establish a cDNA expression cloning system. In two model experiments, murine interleukin (IL)-3-dependent Ba/F3 cells were infected with libraries of retrovirally expressed cDNA derived from human T-cell mRNA or human IL-3-dependent TF-1 cell line mRNA. These infected Ba/F3 cells were selected for the expression of CD2 by flow cytometry or for the alpha subunit of the human IL-3 receptor (hIL-3R alpha) by factor-dependent growth. CD2 (frequency, 1 in 10(4)) and hIL-3R alpha (frequency, 1 in 1.5 x 10(5)) cDNAs were readily detected in small-scale experiments, indicating this retroviral expression cloning system is efficient enough to clone low-abundance cDNAs by their expression or function.

3T3 Cells↗

PubMed1995

Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis.

Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.

Animals↗

PubMed1994

Progression and regression of atherosclerotic findings in the descending thoracic aorta detected by enhanced computed tomography.

Reports evaluating the progression and regression of atherosclerosis by non-invasive procedure are still limited. We investigated the progression and regression of atherosclerotic intimal thickening of the descending thoracic aorta non-invasively measured by enhanced computed tomography in 83 patients (average age 51.0 years) at the beginning and end of a 2.5 year period. The patients were not taking anti-hypertensive, lipid-lowering or hypoglycemic drugs and therefore we consider them as a natural history cohort. At entry, the extent of aortic intimal thickening was 35.2% of the circumference of the cross-section of the wall, which increased to 39.7% after 2.5 years. Spontaneous progression was associated directly with age, elevated levels of total cholesterol, LDL-cholesterol, LDL/HDL cholesterol ratio, diastolic blood pressure, and inversely to HDL-cholesterol. There was little correlation with triglycerides, systolic blood pressure, fasting glucose or body mass index. In 65 of the patients, aortic atherosclerosis progressed, while in 9 patients it remained unchanged, and in a further 9 it regressed. The levels of lipid variables, apart from HDL-cholesterol, and diastolic blood pressure in the patients with spontaneous progression were significantly higher than in the unchanged and spontaneous regression. Thus, this study verified the natural history of aortic atherosclerosis non-invasively measured by enhanced CT.

Adult↗

PubMed1994

[Single dose toxicity study of lactitol (NS-4) in dogs].

Male beagle dogs were orally given lactitol, a hepatic encephalopathy drug, in a single dose of 7.5, 15.0 or 30.0 g/kg. Vomiting was seen within 30 minutes after dosing in all treated groups. Diarrhea was observed 3 or 5 hours after dosing in the 15.0 and 30.0 g/kg dose groups. There were no drug related effects on survival, food and water consumption, body weight gain or tissues and organs.

Administration, Oral↗

PubMed1994

[52-week oral toxicity study of lactitol (NS-4) in dogs followed by 9-week recovery test].

Five male and 5 female beagle dogs were orally given lactitol, a hepatic encephalopathy drug, for 52 weeks at doses of 0, 0.25, 1.25 or 6.25 g/kg/day. A 9 week recovery test was conducted after the discontinuation of the drug treatment. Soft stool, diarrhea, and vomiting were seen in the 1.25 and 6.25 g/kg groups. In the 6.25 g/kg group, bloody stool and increased water consumption were also observed. Urinalysis showed larger amount of the urine volume in the 6.25 g/kg group. The cecum weight of this group was increased without any morphological changes. There were no drug related effects on survival, body weight gain and food consumption. Electrocardiographic, ophthalmoscopic, hematologic and biochemical examinations failed to show any abnormalities related to the drug treatment. The above mentioned changes were satisfactorily reversible. Based on the results obtained, the NOAEL of this study was suggested to be 0.25 g/kg/day.

Administration, Oral↗

PubMed1993

CD4dull+ hematopoietic progenitor cells in murine bone marrow.

CD4+ cells comprise approximately 3% to 6% of murine bone marrow (BM) cells. The majority are CD4dull+, but there are two distinct sub populations: CD4 brightly positive Gr-1- cells (CD4hiGr-1-) and CD4+ Gr-1+ cells (CD4loGr-1lo). CD4hiGr-1- cells are considered to be mature T cells by cell surface antigen expression and morphology. CD4loGr-1lo cells, which comprise approximately 0.6% of the BM cells, express small amount of B220 and Thy1 antigens. Interestingly, colony-forming units (CFU)-spleen and CFU-C are not enriched in this population. However, when injected into lethally irradiated mice, CD4loGr-1lo cells were shown to differentiate into T-cell, B-cell, and myelo-monocyte lineages when assayed 26 weeks after transplantation. Furthermore, donor-derived CD4loGr-1lo cells were present in the recipients' BM at least 16 weeks after transplantation. These observations suggest that murine CD4loGr-1lo cells in BM have self-renewal capability and retain the ability to differentiate into at least three lineages in long-term hematopoiesis.

Animals↗

PubMed1993

[The effect of fluticasone propionate topically dosed prior to the pollen scattering season on cellular infiltration into the surface of nasal mucous membrane in patients with Japanese cedar pollinosis].

In order to examine fluticasone propionate's mechanism of inhibiting nasal allergic symptoms, topical dosing of FP to patients with Japanese cedar pollinosis was started before the pollen scattering season, and the kinetics of basophilic cells and eosinophils which infiltrated into the surface of nasal mucous membrane were observed. Patients with Japanese cedar pollinosis were divided into two groups. Before and in the early period of the pollen scattering season, one group received FP and the other group a placebo, topically into the nostrils. In the mid and late season, both groups were treated with FP topical dosing. The study was carried out in the double blind manner. In the pre-, early and late season, specimens were scraped from the nasal mucosal surface, basophilic cell and eosinophil counts in the specimens were measured, and histamine and ECP contents in the specimens were also determined. Topical use of FP starting pre-season significantly inhibited symptoms of Japanese cedar pollinosis, as well as accumulation of basophilic cells and eosinophils in the nasal mucosal surface. Histamine and ECP contents in the nasal specimens tended to decrease with the topical use of FP.

Administration, Topical↗

PubMed1992

Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Adolescent↗