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1.
J Theor Biol ; 524: 110731, 2021 09 07.
Article in English | MEDLINE | ID: mdl-33915145

ABSTRACT

A plant can sire more seeds by increasing the number of pollen recipient flowers or the amount of pollen deposited on recipient flowers. We theoretically analyzed how pollen stickiness contributes to paternal fitness through changing the pattern of pollen dispersal including both the number of recipient flowers and overall pollen deposition (the overall amount of pollen deposited on recipient flowers) in animal-pollinated plants. We developed a numerical model in which pollen stickiness to pollinators increases with production of expensive materials on pollen surfaces, and a high level of stickiness diminishes the proportions of pollen lost from a pollinator body during a flight and pollen deposited on a stigma during a visit. We found that the number of recipient flowers monotonically increased with increasing pollen stickiness allocation while overall pollen deposition was maximized at a certain amount of stickiness allocation. We demonstrated that evolutionarily stable pollen stickiness attained many recipient flowers at the expense of overall pollen deposition in most cases while it merely favored maximization of overall pollen deposition in all other cases. Sticky pollen evolved if pollinators were highly likely to drop pollen during flights and did not diffuse well. In this situation, the evolutionarily stable pattern of pollen dispersal was acquisition of many pollen recipient flowers rather than maximization of overall pollen deposition. Sticky pollen also evolved if additional sticking elements were moderately effective in increasing the force of adhesion to pollinators. Pollen stickiness has a significant effect on the pattern of pollen dispersal via the extent of pollen carryover, and our results suggest that plants maximize paternal fitness by giving pollen the optimal stickiness, which varies with pollinating partners.


Subject(s)
Flowers , Pollination , Animals , Pollen
2.
Sci Total Environ ; 671: 666-675, 2019 Jun 25.
Article in English | MEDLINE | ID: mdl-30939319

ABSTRACT

Sea surface salinity (SSS) is a key parameter to understand and predict many physical, chemical and biological processes in dynamic coastal environments. Yet, in many regions, instrumental measurements are spatially sparse and insufficiently long, hindering our ability to document changes, causes, and consequences of SSS across different time scales. Therefore, there is an need to develop a robust proxy to extend SSS records back in time. Here, we test whether SSS can be reconstructed reliably and quantitatively from shell oxygen isotopic ratios (δ18Oshell) of the mussel Mytilus galloprovincialis (Lamarck, 1819) in Otsuchi Bay, Northern Japan. δ18Oshell ratios vary spatially and temporally and exhibit strong linear correlations with both sea surface temperature (SST) and SSS measurements, indicating that the composite signal recorded by δ18Oshell measurably responds to variations in both parameters. By combining contemporaneous variations of SST and δ18Oshell, SSS records encoded into mussel shells are deconvolved that significantly correlate with in situ SSS values. To further validate the robustness of δ18Oshell as a quantitative SSS proxy, high-resolution and temporally aligned time-series of δ18Oshell-derived SSS are reconstructed that are highly synchronous with the instrumental records. In particular, two lowered SSS scenarios occur concomitantly with periods of the summer monsoon and typhoon events. δ18Oshell-derived SSS time-series are also comparable to those from numerical modeling. In conclusion, our findings demonstrate that mussel δ18Oshell signatures can be used as a useful tool to construct high-resolution records of SSS in the coastal regions.


Subject(s)
Animal Shells/chemistry , Environmental Monitoring , Mytilus , Water Pollutants/analysis , Animals , Japan , Retrospective Studies , Salinity , Seawater
3.
Oral Dis ; 23(1): 78-83, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27569039

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the possibility of intravenous sedation as a useful pain-relieving option for impacted third molar extractions. SUBJECTS AND METHODS: A prospective cohort study was conducted among patients who underwent bilateral mandibular third molar extractions under local anaesthesia and intravenous sedation (sedation group) and patients who underwent unilateral mandibular third molar extraction under local anaesthesia alone (local anaesthesia group). The frequency of use of postoperative oral analgesia and the intensity of pain assessed using the full cup test were compared between the two groups. RESULTS: The maximum pain intensity (0-100) on postoperative day 1 in the sedation and local anaesthesia groups was 72.8 ± 16.98 and 84.8 ± 15.84, respectively, and the mean pain intensity was 42.2 ± 16.00 and 49.6 ± 18.94. The maximum and mean pain intensities in the sedation group were significantly milder than those in the local anaesthesia group. The number of oral analgesic doses in the sedation group was significantly smaller on the day of surgery and on postoperative day 1 than in the local anaesthesia group. CONCLUSIONS: The results of this study suggest that bilateral impacted mandibular third molar extractions under intravenous sedation could be a recommended treatment option.


Subject(s)
Facial Pain/etiology , Molar, Third/surgery , Pain Management/methods , Tooth Extraction/adverse effects , Tooth, Impacted/surgery , Administration, Intravenous , Adult , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Conscious Sedation/methods , Facial Pain/drug therapy , Female , Humans , Male , Pain Measurement , Pain, Postoperative/drug therapy , Pentazocine/administration & dosage , Pentazocine/therapeutic use
4.
Article in English | MEDLINE | ID: mdl-27063182

ABSTRACT

The prevailing view of Nagaoka's "Saturnian" atom is so misleading that today many people have an erroneous picture of Nagaoka's vision. They believe it to be a system involving a 'giant core' with electrons circulating just outside. Actually, though, in view of the Coulomb potential related to the atomic nucleus, Nagaoka's model is exactly the same as Rutherford's. This is true of the Bohr atom, too. To give proper credit, Nagaoka should be remembered together with Rutherford and Bohr in the history of the atomic model. It is also pointed out that Nagaoka was a pioneer of understanding hyperfine interactions in order to study nuclear structure.


Subject(s)
Models, Theoretical
5.
PLoS One ; 10(12): e0143443, 2015.
Article in English | MEDLINE | ID: mdl-26650121

ABSTRACT

When pollinators use flower color to locate food sources, a distinct color can serve as a reproductive barrier against co-flowering species. This anti-interference function of flower color may result in a community assembly of plant species displaying mutually different flower colors. However, such color dispersion is not ubiquitous, suggesting a variable selection across communities and existence of some opposing factors. We conducted a 30-week study in a plant community and measured the floral reflectances of 244 species. The reflectances were evaluated in insect color spaces (bees, swallowtails, and flies), and the dispersion was compared with random expectations. We found that co-existing colors were overdispersed for each analyzed pollinator type, and this overdispersion was statistically significant for bees. Furthermore, we showed that exclusion of 32 aliens from the analysis significantly increased the color dispersion of native flowers in every color space. This result indicated that aliens disturbed a native plant-pollinator network via similarly colored flowers. Our results demonstrate the masking effects of aliens in the detection of color dispersion of native flowers and that variations in pollinator vision yield different outcomes. Our results also support the hypothesis that co-flowering species are one of the drivers of color diversification and affect the community assembly.


Subject(s)
Color , Flowers , Pollination , Animals , Bees , Introduced Species , Lepidoptera , Plants , Population Dynamics , Reproduction
6.
Naturwissenschaften ; 100(7): 659-66, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23793296

ABSTRACT

An individual pollinator may tend to consecutively probe more flowers on a plant to which it returns at shorter intervals than other plants. In a large net cage, I let individually marked bumble bees forage on flowering heads of red clovers arranged in 37 bottles (plants), each of which was monitored by an observer to record every visit and probe for 2.5 h on each of 3 days. The data of collective visits by marked individuals revealed that the bees had their own foraging areas, in which they visited a set of plants frequently and others less often, i.e., the same individual bee repeatedly returned to certain plants as a regular visitor while sampling others as an occasional visitor. I further found that as a regular visitor, an individual bee tended to probe more flowering heads on familiar plants while probing fewer on unfamiliar plants as an occasional visitor. The mean number of consecutive probes by a bee was also positively correlated with its activity (the total number of plant visits made during the observation period). The fact that each bee behaves differently on different plants indicates that the same individual pollinator can exert different influence on the reproductive success of each plant: apparently, a pollinator likely reduces the potential for geitonogamous self-pollination when foraging as an occasional visitor. Attracting occasional visitors therefore may be beneficial for plants to avoid geitonogamy. This study thus emphasizes the importance of paying attention to pollinator individuality in pollination ecology.


Subject(s)
Bees/physiology , Behavior, Animal/physiology , Flowers/physiology , Animals , Time
7.
Proc Natl Acad Sci U S A ; 107(5): 1833-7, 2010 Feb 02.
Article in English | MEDLINE | ID: mdl-20080684

ABSTRACT

Decadal-scale climate variations over the Pacific Ocean and its surroundings are strongly related to the so-called Pacific decadal oscillation (PDO) which is coherent with wintertime climate over North America and Asian monsoon, and have important impacts on marine ecosystems and fisheries. In a near-term climate prediction covering the period up to 2030, we require knowledge of the future state of internal variations in the climate system such as the PDO as well as the global warming signal. We perform sets of ensemble hindcast and forecast experiments using a coupled atmosphere-ocean climate model to examine the predictability of internal variations on decadal timescales, in addition to the response to external forcing due to changes in concentrations of greenhouse gases and aerosols, volcanic activity, and solar cycle variations. Our results highlight that an initialization of the upper-ocean state using historical observations is effective for successful hindcasts of the PDO and has a great impact on future predictions. Ensemble hindcasts for the 20th century demonstrate a predictive skill in the upper-ocean temperature over almost a decade, particularly around the Kuroshio-Oyashio extension (KOE) and subtropical oceanic frontal regions where the PDO signals are observed strongest. A negative tendency of the predicted PDO phase in the coming decade will enhance the rising trend in surface air-temperature (SAT) over east Asia and over the KOE region, and suppress it along the west coasts of North and South America and over the equatorial Pacific. This suppression will contribute to a slowing down of the global-mean SAT rise.

9.
Cytotherapy ; 6(6): 543-53, 2004.
Article in English | MEDLINE | ID: mdl-15770794

ABSTRACT

BACKGROUND: BM-derived mesenchymal stem cells (MSC) are attractive sources for autotransplantation with no risk of rejection, but the use of these cells bas problems, including the necessity of harvesting BM from donors, the donors' age-dependency, limitation to autologous use and difficulty of use for patients with hereditary diseases. We report a method of isolating placenta-derived mesenchymal progenitor cells (PDMPC) that can be used as an alternative source of MSC. METHODS: We isolated PDMPC from human fetal chorionic villi using the explant culture method, from placentas collected after neonatal delivery (38-40 weeks of gestation). The PDMPC were characterized by morphologic and immunophenotypic analysis. The differentiation ability of mesenchymal and neural lineages was detected using specific culture conditions and determined by morphology, reverse transcription(RT)-PCR, histochemical staining and immunocytostaining. RESULTS: The PDMPC all originated from fetal chorionic villi, as confirmed by fluorescence in situ hybridization analysis. The PDMPC population consisted of spindle-shaped cells and large flat cells. The PDMPCexpressed CD13, CD44, CD73, CD90, CDIO5 and HLA class I as surface epitopes, but not CD31, CD34, CD45 and HLA-DR. These cells differentiated into osteocytes, chondrocytes and adipocytes under specific culture conditions, and were also induced to form neural-like cells. DISCUSSION: Our study shows that PDMPC can differentiate into mesenchymal lineages and be induced to form neural-like cells. Thus, PDMPCisolated from chorionic villi of placenta may provide a novel source for the research of stem and progenitor cells in placenta, cell therapy and regenerative medicine, particularly as a source of allogenic mesenchymal stem and progenitor cells with little ethical conflict and various advantages


Subject(s)
Chorionic Villi , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Antigens, CD/metabolism , Biomarkers , Cell Differentiation , Cell Separation , Female , HLA Antigens/analysis , Humans , Immunophenotyping , Male , Mesenchymal Stem Cells/immunology , Neurons/cytology , Neurons/physiology , Pregnancy , Stem Cell Transplantation
10.
FEBS Lett ; 468(2-3): 234-8, 2000 Feb 25.
Article in English | MEDLINE | ID: mdl-10692593

ABSTRACT

Lymphocyte-oriented kinase (LOK) is a member of the STE20/p21-activated kinase (PAK) family and expressed predominantly in lymphoid organs. Generation of LOK-deficient mice revealed that the leukocyte-function-associated antigen (LFA-1)/intercellular adhesion molecules (ICAM)-mediated aggregation of mitogen-stimulated T cells was greatly enhanced in the absence of LOK. Though levels of total LFA-1 and ICAMs as well as the active form of LFA-1 on T cell blasts were comparable in the presence and absence of LOK, clustering of active LFA-1 detected by binding of soluble ICAM-1 was accelerated in the absence of LOK. These results suggest that LOK is potentially involved in the regulation of LFA-1-mediated lymphocyte adhesion.


Subject(s)
Intercellular Adhesion Molecule-1/physiology , Lymphocyte Function-Associated Antigen-1/physiology , Protein Serine-Threonine Kinases/deficiency , Protein Serine-Threonine Kinases/metabolism , T-Lymphocytes/physiology , Animals , Cell Adhesion , Cells, Cultured , Concanavalin A , Genomic Library , Lymph Nodes/immunology , Lymphocyte Activation , Mice , Mice, Knockout , Protein Serine-Threonine Kinases/genetics , Restriction Mapping , T-Lymphocytes/cytology , T-Lymphocytes/immunology
11.
J Immunol Methods ; 228(1-2): 69-79, 1999 Aug 31.
Article in English | MEDLINE | ID: mdl-10556544

ABSTRACT

The importance of the interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in the progression of inflammatory responses in vivo has been demonstrated mainly in rats. The present study was undertaken to develop binding assays suitable for measuring the rat ICAM-1/LFA-1 interaction in vitro. We first examined binding of rat T lymphoma FTL43 cells, which express LFA-1, to immobilized rat ICAM-1. Although FTL43 cells bound avidly to immobilized ICAM-1 and the binding was abolished with anti-LFA-1 monoclonal antibodies (mAbs), the binding was not completely inhibited by most anti-ICAM-1 mAbs. We next purified rat LFA-1 from FTL43 cells and constructed a cell-free binding assay. By using a newly developed anti-rat LFA-1 mAb RL14/9, which does not inhibit ICAM-1/LFA-1 interactions, binding of purified rat LFA-1 to immobilized ICAM-1 was successfully detected, whereas only a low signal to noise ratio was observed when binding of ICAM-1 to immobilized LFA-1 was examined. Moreover, we found that simultaneous addition of purified LFA-1 and biotinylated RL14/9 to ICAM-1-coated wells resulted in more sensitive detection of rat ICAM-1/LFA-1 binding. The binding was completely blocked with both anti-LFA-1 and anti-ICAM-1 mAbs and was much more sensitive to inhibition by the ICAM-1-IgG chimera, as compared with the cell-based assay. These results indicate that the cell-free binding assay provides a rapid and sensitive method for screening rat ICAM-1/LFA-1 antagonists, whose therapeutic effect on inflammatory diseases can further be evaluated in vivo.


Subject(s)
Antibodies, Monoclonal , Immunoassay/methods , Intercellular Adhesion Molecule-1/metabolism , Lymphocyte Function-Associated Antigen-1/immunology , Lymphocyte Function-Associated Antigen-1/metabolism , Animals , Cell Line , Cell-Free System , Evaluation Studies as Topic , In Vitro Techniques , Inflammation/etiology , Inflammation/immunology , Inflammation/metabolism , Lymphocyte Function-Associated Antigen-1/isolation & purification , Mice , Protein Binding , Rats
13.
Hua Xi Yi Ke Da Xue Xue Bao ; 30(3): 318-20, 323, 1999 Sep.
Article in Chinese | MEDLINE | ID: mdl-12212296

ABSTRACT

To study the characteristics of the mesenchymal cells of ameloblastic fibrosarcoma (AFS), three cases of AFS were studied immunohistochemically and ultrastructurally. The results showed that the mesenchymal component of AFS consisted predominantly of fibroblastic cells with a small number of undifferentiated cells, a few histiocytes and occasionally myofibroblastic cells under electron microscope. The fibroblastic cells were Vimentin positive only, and myofibroblastic cells were positive for Vimentin, HHF35 and alpha-SMA. The histiocytes were positive both for kp1 and PG-M1, suggesting that these cells were infiltrating cells from peripheral blood rather than histiocytic differentiation of tumor cells. Compared with ameloblastic fibroma, AFS showed much higher PCNA labeling index, suggesting higher proliferation activity of AFS.


Subject(s)
Jaw Neoplasms/ultrastructure , Odontogenic Tumors/ultrastructure , Odontoma/ultrastructure , Fibrosarcoma/metabolism , Fibrosarcoma/ultrastructure , Humans , Jaw Neoplasms/metabolism , Odontogenic Tumors/metabolism , Odontoma/metabolism
14.
J Immunol ; 161(8): 4016-22, 1998 Oct 15.
Article in English | MEDLINE | ID: mdl-9780171

ABSTRACT

LFA-1 is a member of the beta2 integrin family, and interacts with ICAM-1, a member of the Ig superfamily containing five Ig-like domains. Interaction of LFA-1 with ICAM-1 is important in a number of cellular events, including Ag-specific T cell activation and leukocyte transendothelial migration, which are known to be typically transient and highly regulated. In this study, we have used surface plasmon resonance technology to study the ICAM-1/LFA-1 interaction at the molecular level. A soluble form of LFA-1 (sLFA-1), normally expressed as two noncovalently associated membrane-bound subunits, has been produced, and its interaction with ICAM-1 has been examined. The kinetic analysis of a monomeric sLFA-1 binding to the first two domains of ICAM-1 expressed as a chimeric IgG fusion protein (D1D2-IgG) revealed that sLFA-1 was bound to the D1D2-IgG chimera with a Kd of 500 nM and dissociated with a k(diss) of 0.1 s(-1). Monomeric membrane-bound LFA-1 purified from plasma membranes showed a similar kinetic to sLFA-1. These results suggest that the monovalent interaction between ICAM-1 and LFA-1 has a primarily high affinity and a slow dissociation rate constant as compared with other adhesion molecules, suggesting a potential mechanism for firm adhesion.


Subject(s)
Intercellular Adhesion Molecule-1/metabolism , Lymphocyte Function-Associated Antigen-1/metabolism , Animals , Binding Sites , CHO Cells , Cricetinae , Humans , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/immunology , Lymphocyte Function-Associated Antigen-1/genetics , Lymphocyte Function-Associated Antigen-1/immunology , Protein Binding , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism
15.
J Biol Chem ; 273(41): 26698-704, 1998 Oct 09.
Article in English | MEDLINE | ID: mdl-9756912

ABSTRACT

An approximately 120-amino acid domain present generally at the NH2 termini, termed the POZ domain, is highly conserved in various proteins with zinc finger DNA binding motifs. We have isolated a novel protein sharing homology with the POZ domain of a number of zinc finger proteins, including the human BCL-6 protein. By using a binding site selection technique (CAST), a high affinity binding site of the protein was determined to be (A/C)ACATCTG(G/T)(A/C), containing the E box core sequence motif. The protein was shown to repress transcription from a promoter linked to its target sequences and was hence named RP58 (Repressor Protein with a predicted molecular mass of 58 kDa). Immunogold electron microscopic study revealed that almost all RP58 is localized in condensed chromatin regions. These observations demonstrate for the first time that a protein mediating a sequence-specific transcriptional repression associates with highly condensed chromatin. We suggest that RP58 may be involved in a molecular link between sequence-specific transcriptional repression and the organization of chromosomes in the nucleus.


Subject(s)
Chromatin/metabolism , Repressor Proteins/metabolism , Transcription Factors/metabolism , Transcription, Genetic , Amino Acid Sequence , Animals , Base Sequence , Binding Sites , COS Cells , Cloning, Molecular , Consensus Sequence , DNA , Humans , Microscopy, Electron , Molecular Sequence Data , Repressor Proteins/genetics , Transcription Factors/genetics
16.
J Immunol Methods ; 212(1): 61-8, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9671153

ABSTRACT

The interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is of importance in a number of cellular events, including antigen-specific T cell activation and emigration of leukocytes into sites of inflammation. We describe here the first use of a recombinant soluble form of human LFA-1 (sLFA-1) for the measurement of the binding between LFA-1 and ICAM-1. sLFA-1 has been successfully expressed and purified. The expressed sLFA-1 was shown to be functionally active by their binding to ICAM-1. Binding of sLFA-1 to ICAM-1 was observed by receptor binding assay. Both monomeric (soluble ICAM-1 or the first two domains of ICAM-1) and dimeric ICAM-1 (IgG chimera of each ICAM-1 fragment) showed inhibitory activity on assay with IC50 values of 400 nM and 40 nM, respectively. These results suggest that the soluble constructs would be useful tools for molecular analysis of ICAM-1/LFA-1 interaction as well as in screening for ICAM-1/LFA-1 antagonists.


Subject(s)
CD18 Antigens/metabolism , Intercellular Adhesion Molecule-1/metabolism , Lymphocyte Function-Associated Antigen-1/metabolism , CD18 Antigens/genetics , CD18 Antigens/isolation & purification , Cloning, Molecular , DNA, Complementary , Humans , Intercellular Adhesion Molecule-1/genetics , Lymphocyte Function-Associated Antigen-1/genetics , Lymphocyte Function-Associated Antigen-1/isolation & purification , Peptide Fragments/genetics , Peptide Fragments/metabolism , Protein Binding , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Solubility
17.
Mol Pharmacol ; 53(6): 1097-103, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9614214

ABSTRACT

We have recently identified 8-difluoromethoxy-1-ethyl-6-fluoro-1, 4-dihydro-7-[4-(2-methoxyphenyl)-1-piperazinyl]-4-oxoquinoline-3-carb oxylic acid (K-12) as a potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) transcription. In the search for more effective derivatives and their mode of action, we have found 7-(3,4-dehydro-4-phenyl-1-piperidinyl)-1, 4-dihydro-6-fluoro-1-methyl-8-trifluoromethyl-4-oxoquinoline-3- carboxylic acid (K-37) and 8-difluoromethoxy-1,4-dihydro-6-fluoro-7-(3, 4-dehydro-4-phenyl-1-piperidinyl)1-[4,(1,2, 4-triazol-1-yl)methylphenyl]-4-oxoquinoline-3-carboxylic acid (K-38) to be more potent inhibitors of HIV-1 replication than K-12. The EC50 values of K-37 and K-38 for HIV-1IIIB were 27 and 3.8 nM in peripheral blood mononuclear cells, respectively. These values were approximately 3- and 24-fold lower than the EC50 of K-12. K-38 was also a more potent inhibitor of HIV-1 replication in chronically infected cells, such as tumor necrosis factor alpha-stimulated OM-10. 1 cells. K-37 and K-38 proved to be more cytotoxic than K-12 for a variety of cell lines as well as peripheral blood mononuclear cells. These compounds were more inhibitory of Tat-induced HIV-1 long terminal repeat-driven gene expression than K-12, which suggests that their mechanism of action is attributable in part to the inhibition of Tat function. Interestingly, K-37 and K-38 could suppress the production of tumor necrosis factor alpha and interleukin 6 in phytohemagglutinin-stimulated peripheral blood mononuclear cells and the expression of intercellular adhesion molecule 1 in tumor necrosis factor alpha-stimulated human umbilical vein endothelial cells at their nontoxic concentrations. In contrast, another K-12 derivative, 1, 4-dihydro-8-dimethylaminomethyl-6-fluoro-7-[4-(2-methoxyphenyl)-1-pip eradinyl]-1-methyl-4-oxoquinoline-3-carboxylic acid (K-42), had anti-HIV-1 activity and cytotoxicity profiles similar to those of K-12, but K-42 scarcely inhibited the cytokine production and intercellular adhesion molecule 1 expression.


Subject(s)
Anti-HIV Agents/pharmacology , Cytokines/biosynthesis , HIV-1/drug effects , Quinolines/pharmacology , Virus Replication/drug effects , Cell Line , Gene Products, tat/physiology , Humans , Intercellular Adhesion Molecule-1/analysis , Transcriptional Activation/drug effects , tat Gene Products, Human Immunodeficiency Virus
18.
J Exp Med ; 187(9): 1537-42, 1998 May 04.
Article in English | MEDLINE | ID: mdl-9565645

ABSTRACT

Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4-mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6-/-) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6-/- mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.


Subject(s)
Bronchial Hyperreactivity/immunology , Eosinophils/immunology , Inflammation/immunology , Signal Transduction/physiology , Trans-Activators/deficiency , Animals , Disease Models, Animal , Hypersensitivity/immunology , Immunoglobulin E/blood , Immunoglobulin M/blood , Lung/cytology , Lung/immunology , Mice , Mice, Inbred Strains , Mice, Knockout , Ovalbumin/immunology , STAT6 Transcription Factor
19.
Am J Physiol ; 273(1 Pt 2): H138-47, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9249484

ABSTRACT

The present study aimed to demonstrate constitutive expression of the intercellular adhesion molecule (ICAM)-1 among arterioles, capillaries, and venules in the mesentery and liver and to examine the interaction between cultured endothelial cells and leukocytes in rats. ICAM-1 expression in the microvessels in vivo was visually demonstrated by laser confocal fluorescence microscopy. A monoclonal antibody against rat ICAM-1 (1A29) was labeled with fluorescein isothiocyanate, and the binding ratio between the fluorescence and immunoglobulin was determined for data calibration. Intravascularly administered fluorescein isothiocyanate-labeled 1A29 was distributed heterogeneously among the hierarchy of microvessels in the mesentery: postcapillary venules were the major portion expressing ICAM-1 constitutively, and the density of 1A29 bound to their endothelium was at least 10 times higher than that in true capillaries and arterioles in the same mesentery. On the other hand, the liver expressed ICAM-1 abundantly in sinusoids to the extent similar to that in central venules. These results suggest that postcapillary venules serve as an active gateway with the readiness to help adhere circulating leukocytes exposed to proinflammatory stimuli in acute inflammation.


Subject(s)
Cell Adhesion , Endothelium, Vascular/physiology , Intercellular Adhesion Molecule-1/biosynthesis , Leukocytes/physiology , Animals , Animals, Newborn , Arterioles , Capillaries , Cell Adhesion/drug effects , Cells, Cultured , Coculture Techniques , Endothelium, Vascular/cytology , Fluorescein-5-isothiocyanate , Liver Circulation , Male , Microscopy, Confocal/methods , N-Formylmethionine Leucyl-Phenylalanine/pharmacology , Rats , Rats, Wistar , Splanchnic Circulation , Venules
20.
Nihon Kyobu Shikkan Gakkai Zasshi ; 34 Suppl: 111-4, 1996 Dec.
Article in Japanese | MEDLINE | ID: mdl-9216197

ABSTRACT

Recent results from molecular biology have shown that lung cancer is characterized by multiple, sequentially appearing molecular changes that include genetic and epigenetic alterations. Among all types of lung cancer, small cell lung cancer (SCLC) is associated with the lowest rate of 5-year survival. In this symposium, we introduce our findings regarding the c-kit oncogenes in SCLC. We found that the c-kit gene is strongly expressed in SCLC. The c-kit gene was not expressed in normal bronchial epithelial cells, which indicates that this gene is abberantly transcribed in SCLC. In addition, c-kit-positive cases of SCLC showed autophosphorylation in response to recombinant human stem cell factor. Furthermore, adding rh stem cell factor of SCLC cell lines induced a significant chemotactic response and moderate in vitro cell growth. These results strongly suggest that abnormal expression of the c-kit gene may be involved in the pathogenesis of SCLC by autocrine/paracrine stimulation via the c-kit/SCF signal pathway. To overcome drug resistance, we assessed the efficacy of a chimeric toxin targeted to c-kit receptors.


Subject(s)
Carcinoma, Small Cell/therapy , Immunotoxins/therapeutic use , Lung Neoplasms/therapy , Carcinoma, Small Cell/genetics , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Proto-Oncogene Proteins c-kit/genetics , Stem Cell Factor/metabolism
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