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1.
J Geophys Res Space Phys ; 123(3): 2424-2440, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29938155

ABSTRACT

We use a set of ground-based instruments (Global Positioning System receivers, ionosondes, magnetometers) along with data of multiple satellite missions (Swarm, C/NOFS, DMSP, GUVI) to analyze the equatorial and low-latitude electrodynamic and ionospheric disturbances caused by the geomagnetic storm of 22-23 June 2015, which is the second largest storm in the current solar cycle. Our results show that at the beginning of the storm, the equatorial electrojet (EEJ) and the equatorial zonal electric fields were largely impacted by the prompt penetration electric fields (PPEF). The PPEF were first directed eastward and caused significant ionospheric uplift and positive ionospheric storm on the dayside, and downward drift on the nightside. Furthermore, about 45 min after the storm commencement, the interplanetary magnetic field (IMF) Bz component turned northward, leading to the EEJ changing sign to westward, and to overall decrease of the vertical total electron content (VTEC) and electron density on the dayside. At the end of the main phase of the storm, and with the second long-term IMF Bz southward turn, we observed several oscillations of the EEJ, which led us to conclude that at this stage of the storm, the disturbance dynamo effect was already in effect, competing with the PPEF and reducing it. Our analysis showed no significant upward or downward plasma motion during this period of time; however, the electron density and the VTEC drastically increased on the dayside (over the Asian region). We show that this second positive storm was largely influenced by the disturbed thermospheric conditions.

2.
Eye (Lond) ; 19(4): 464-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15184935

ABSTRACT

PURPOSE: To investigate the in vivo effects of tissue factor pathway inhibitor 2 (TFPI-2), which stimulates proliferation of retinal pigment epithelial cells, but not the proliferation of fibroblast and vascular endothelial cells in vitro, on retinal degeneration using a sodium-iodate (SI)-induced model in rabbits and Royal Collage of Surgeons (RCS) rats. METHODS: 79 microg of recombinant TFPI-2 (rTFPI-2) or vehicle alone was injected intravitreously to 18 eyes of 12 pigmented rabbits a day after 20 mg/kg of SI was intravenously administered. Retinal function was assessed 4, 7, 14, and 21 days after the injection by analysing amplitudes of the c-wave of a bright flash electroretinogram. Additionally, 10 microg of rTFPI-2 or vehicle alone was injected intravitreously to 11 eyes of RCS rats at both 3 and 4 weeks old, then the retina was examined histologically at 5 weeks old. RESULTS: The rTFPI-2-treated eyes in rabbits showed a significantly less decrease in the relative amplitude of the c-wave than control eyes on days 4 and 7. The thickness of the outer nuclear layer was significantly thicker and the vacuole in the photoreceptor layer was less frequently observed in the rTFPI-2-treated RCS rats than the controls. CONCLUSIONS: Intravitreal injection of TFPI-2 rescues SI-induced retinal degeneration in rabbits and naturally occurring retinal degeneration in RCS rats at least partly. These results may suggest that this compound can be utilized in the treatment of retinal degeneration.


Subject(s)
Glycoproteins/therapeutic use , Retinal Degeneration/drug therapy , Animals , Disease Models, Animal , Electroretinography , Injections , Iodates , Male , Pigment Epithelium of Eye/drug effects , Pigment Epithelium of Eye/pathology , Rabbits , Recombinant Proteins/therapeutic use , Retinal Degeneration/chemically induced , Retinal Degeneration/pathology , Vitreous Body
3.
Cell Immunol ; 211(1): 71-9, 2001 Jul 10.
Article in English | MEDLINE | ID: mdl-11585390

ABSTRACT

It has been reported that the three-dimensional structure of thymic epithelial cells (TECs) is responsible for thymic positive selection but that this ability disappears when TECs are cultured in monolayer. These results have supported the hypothesis that certain TEC-specific molecules are extinguished during monolayer culture. In this study, using MHC class II-restricted T-cell receptor transgenic mice, we demonstrated that preselected CD4(+)8(+) (DP) thymocytes were inhibited from developing into CD4(+)8(-) (CD4SP) cells in reaggregate thymus organ culture with monolayer-cultured TECs, but this inhibition was removed when TECs were cultured in monolayer with protein synthesis inhibitor or when the cultured TECs were treated with fixative. These results seem to be inconsistent with the previous hypothesis and indicate that monolayer culture allows TECs to retain the surface molecules necessary for positive selection but interferes with their function, which must be sustained for three dimensional structure.


Subject(s)
Epithelial Cells/physiology , T-Lymphocytes/immunology , Thymus Gland/cytology , Thymus Gland/immunology , Animals , Cell Differentiation , Cells, Cultured , Cycloheximide/pharmacology , Epithelial Cells/cytology , Epithelial Cells/drug effects , Fixatives/chemistry , Interleukin-2/biosynthesis , Membrane Proteins/physiology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Organ Culture Techniques/methods , Protein Synthesis Inhibitors/pharmacology , Receptors, Antigen, T-Cell/genetics , Stromal Cells/physiology
4.
Immunol Lett ; 71(1): 61-6, 2000 Jan 10.
Article in English | MEDLINE | ID: mdl-10709787

ABSTRACT

To overcome low efficiency of retroviral infection into immature T cells, we modified reaggregation fetal thymus organ culture by closely packed co-culture with virus-producing cells (VPC). The viral vector was constructed in chimeric vector, pMX, with IRES and tailless-rat CD2 as a surface marker of infected cells. A rearranged TCR beta gene (Vbeta8.2) was further inserted into the construct for investigating effect of the introduced gene in T cell development. Using this system, we succeeded to transfer the viral vector into immature thymocytes at a remarkably higher efficiency compared to conventional methods using medium containing retrovirus. Moreover, the introduced TCR beta gene was expressed on thymocytes of RAG2-deficient mice to induce in the transition of CD4-CD8- double-negative (DN) into CD4+CD8+ double-positive (DP) cells by transducing beta-selection signaling. Thus, our modified reaggregation culture system is useful for studying the molecular mechanism of T cell development due to a highly efficient gene transfer into immature T cells.


Subject(s)
Cell Culture Techniques/methods , Genetic Vectors , Retroviridae/genetics , T-Lymphocytes/cytology , Transfection/methods , Animals , CD2 Antigens/genetics , Cells, Cultured , Coculture Techniques/methods , Mice , Organ Culture Techniques , Rats , Thymus Gland
5.
Int J Biol Macromol ; 26(2-3): 95-101, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10517515

ABSTRACT

Removal of protamine from DNA-protamine (salmine, protamine from salmon sperm) complexes by nucleoplasmin was examined and compared with that of poly-L-glutamic acid (PLGA) using turbidity and ethidium bromide (EB) treatment methods. When nucleoplasmin or PLGA was added to a DNA-protamine complex solution, turbidity was decreased and the amount of EB intercalated into DNA was increased. These results suggest that nucleoplasmin and PLGA can remove protamine from DNA-protamine complexes. The effect of nucleoplasmin was more potent than that of PLGA. Direct interaction of nucleoplasmin with protamine was confirmed by mixing experiments using circular dichroism (CD) and fluorescence spectroscopies. Results suggest that nucleoplasmin is bound to protamine in a 1:1 ratio and that Trp126 is located near a hydrophilic region containing a polyglutamic acid tract of nucleoplasmin which was obviously influenced by its binding with protamine. It would appear that the polyglutamic acid tract in nucleoplasmin plays a critical role for binding with protamine.


Subject(s)
DNA/metabolism , Nuclear Proteins/metabolism , Phosphoproteins/metabolism , Protamines/metabolism , Spermatozoa/physiology , Animals , Circular Dichroism , DNA/drug effects , Ethidium/chemistry , Male , Nuclear Proteins/pharmacology , Nucleoplasmins , Phosphoproteins/pharmacology , Polyglutamic Acid/pharmacology , Protamines/drug effects , Protamines/isolation & purification , Salmon , Solutions , Spectrometry, Fluorescence , Spermatozoa/drug effects
6.
Int Immunol ; 11(1): 89-97, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10050677

ABSTRACT

The differentiation process from CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) stage is accompanied by vigorous proliferation. The resulting DP cells contain a sizable proportion of large cycling cells, but most DP cells are small resting cells. To explore the molecular mechanisms which regulate cell proliferation of DP thymocytes prior to further development, we used TCR-transgenic (Tg) mice with non-selecting MHC (Tg-Neut), which contain almost exclusively DP thymocytes that are not subject to either positive or negative selection. In Tg-Neut, the thymus contained DP cells of relatively large size, which showed higher extracellular signal-regulated kinase activity and enhanced responsiveness to mitogen compared to small DP cells. This indicates that all the large DP cells in the thymus are not positively selected and that they possess proliferative potential. When Tg-Neut mice were backcrossed with CD45 knockout mice (CD454-/- Tg-Neut), the thymus showed an increase of large DP cells and cycling cells, but a decrease of apoptotic cells. Furthermore, Bcl-2 expression and Jun N-terminal kinase activity, which are associated with resistance to apoptosis, were enhanced. These observations suggest that thymocyte proliferation in the DP stage is suppressed by a CD45-related process with regulation of mitogen-activated protein kinase and Bcl-2 unless DP cells receive TCR-mediated signals.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Leukocyte Common Antigens/immunology , Mitogen-Activated Protein Kinases , Receptors, Antigen, T-Cell/genetics , Thymus Gland/immunology , Animals , Apoptosis , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/drug effects , Calcium-Calmodulin-Dependent Protein Kinases/analysis , Cell Differentiation , Cell Division , Cell Size , Crosses, Genetic , Major Histocompatibility Complex , Mice , Mice, Transgenic , Mitogen-Activated Protein Kinase 1/analysis , Mitogen-Activated Protein Kinase 3 , Mitogens/pharmacology , Thymus Gland/cytology
7.
Int Immunol ; 10(8): 1203-10, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9723707

ABSTRACT

Antigen stimulation via TCR in mature T cells provides rapid induction of tyrosine phosphorylation of intracellular substrates including ZAP-70. To study the potential involvement of tyrosine phosphorylation in CD4+CD8+ [double-positive (DP)] thymocytes in the positive selection process in vivo, we isolated and analyzed them in the presence of phosphatase inhibitor. DP thymocytes were obtained from TCR transgenic mice (TCR-Tg) expressing MHC class I- or class II-restricted TCR in selecting and non-selecting MHC backgrounds respectively. The phosphorylation of ZAP-70 in DP thymocytes of class I-restricted TCR-Tg was significantly higher in the positively selecting background than in the non-selecting one. However, such a phosphorylation difference between selecting and non-selecting TCR-Tg was found to be considerably less in class II-restricted TCR-Tg. A similar bias for ZAP-70 phosphorylation was also observed on selecting DP thymocytes when I-A(beta) deficient- and beta2-microglobulin-deficient mice were compared. These ex vivo studies suggest that TCR-mediated signaling on DP thymocytes induces ZAP-70 phosphorylation under a different manner of engagement of TCR to class I and class II molecules in the positive selection process.


Subject(s)
CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Phosphotyrosine/metabolism , Protein-Tyrosine Kinases/metabolism , T-Lymphocyte Subsets/metabolism , Animals , Antibodies, Monoclonal , CD3 Complex/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Histocompatibility Antigens/immunology , Isoenzymes/metabolism , Major Histocompatibility Complex/immunology , Membrane Proteins/metabolism , Mice , Mice, Transgenic , Phospholipase C gamma , Phosphorylation , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/physiology , Signal Transduction , T-Lymphocyte Subsets/immunology , Thymus Gland/immunology , Thymus Gland/metabolism , Type C Phospholipases/metabolism , Vanadates/pharmacology , ZAP-70 Protein-Tyrosine Kinase , beta 2-Microglobulin/immunology
8.
Eur J Immunol ; 28(4): 1368-78, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9565377

ABSTRACT

T cell receptor (TCR) genes are rearranged and expressed in an ordered manner during T cell development. The basic mechanism regulating this stepwise DNA alteration is poorly understood. To address this issue, we explored the presence of a stage-specific element for germ-line transcription of the TCR alpha gene which is closely associated with gene rearrangement. First, germ-line transcription of the TCR alpha gene including the first segment of the J alpha locus, J alpha49, was delayed compared to that of the TCR beta gene in both normal and TCR-transgenic (Tg) mice. Furthermore, expression of this transcript could be induced by CD3epsilon-mediated signals in recombination-activating gene (RAG)-2-deficient mice. In TCR-Tg mice, the endogenous J alpha49 germ-line transcript could not yet be observed at the CD25+ double-negative (DN) stage when the TCR alpha transgene was expressed. Of immature T cell hybridomas derived from either scid thymocytes (CD25+ DN) or immature CD8-single positive (ISP) thymocytes, only the latter hybridoma expressed the J alpha49 germ-line transcript. These data indicate that the J alpha49 germ-line transcription occurs only at a specific developmental stage. Second, to determine which elements may be regulating stage specificity, we performed transient transfection analysis with a reporter gene and demonstrated that the upstream region of the J alpha49 locus possesses promoter activity in correlation with germ-line transcription in ISP-derived but not in SCID-derived hybridomas. These results indicate that the expression of TCR alpha germ-line transcripts is regulated in a stage-specific manner by a cis-element located within the J alpha locus.


Subject(s)
Gene Rearrangement, T-Lymphocyte , Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocytes/immunology , Transcription, Genetic , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Gene Transfer Techniques , Mice , Mice, Inbred C57BL , Promoter Regions, Genetic , Receptors, Antigen, T-Cell, alpha-beta/immunology
9.
Biochemistry ; 36(40): 12071-9, 1997 Oct 07.
Article in English | MEDLINE | ID: mdl-9315845

ABSTRACT

The post-translational modification of core histones plays an essential role in chromatin remodeling processes. We recently reported the occurrence of a novel histone modification, involving a epsilon-(gamma-glutamyl)lysine cross-link between a glutamine residue of histone H2B and a lysine residue of histone H4 in the testis of the starfish, Asterina pectinifera[Shimizu, T., Hozumi, K., Horiike, S., Nunomura, K., Ikegami, S., Takao, T., and Shimonishi, Y. (1996) Nature 380, 32]. In order to determine the complete structure of the modified histone heterodimer, p28 from both testis and sperm was purified. p28 was digested with Achromobacter lyticus protease I or Staphylococcus aureus V8 protease to give proteolytic fragments that were separated by HPLC. Amino acid analysis, sequencing, and mass spectrometric analysis of the fragments showed that the amino acid sequences of these fragments are identical to those of both histones H2B and H4, except for two NH2-terminal peptides obtained by digestion with A. lyticus protease I. One of the peptides, K8, was identical to that reported previously, and the other was a here-to-fore unidentified peptide, which was designated K10. Amino acid and positive-ion FAB-MS/MS analyses of K10 showed that it to be a fragment, derived from Gly8-Lys10 of histone H2B and Gly9-Lys16 of histone H4. The yields of K8 and K10 were calculated to be 47 and 42%, respectively, expressed as the percent of the total amount of p28 used in the experiment. Based on these data, the structure of p28 was determined to be a heterodimer, composed of histones H2B and H4, formed through a transglutaminase-catalyzed acyl transfer reaction between Gln9 of histone H2B and Lys5 or Lys12 of histone H4.


Subject(s)
Histones/chemistry , Spermatozoa/chemistry , Amino Acid Sequence , Animals , Cross-Linking Reagents , Dimerization , Glutamine/chemistry , Histones/isolation & purification , Lysine/chemistry , Magnetic Resonance Spectroscopy , Male , Molecular Sequence Data , Serine Endopeptidases , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Starfish
10.
Int J Biol Macromol ; 20(3): 171-8, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9218166

ABSTRACT

Nucleoplasmin was isolated from Xenopus laevis eggs and purified by an improved method using an open column. Its conformation was investigated spectrophotometrically by UV, CD and fluorescence. It was shown that alpha-helix content of nucleoplasmin was 30-40%, and one of the two tryptophan residues in nucleoplasmin located in the hydrophobic surroundings and the other in the relatively hydrophilic surroundings. The isolated nucleoplasmin was found to decondense sperm nuclei of salmon also, suggesting a possibility of the existence of nucleoplasmin-like protein in fish as well. Collapse of the protamine (salmine)-DNA complex as a simple model for fish sperm nuclei by nucleoplasmin was directly observed by measuring OD320 of aqueous protamine-DNA mixtures. This is a molecular level observation for the removal of protamine from DNA-protamine complex.


Subject(s)
Cell Nucleus/metabolism , DNA/metabolism , Nuclear Proteins/metabolism , Phosphoproteins/metabolism , Protamines/metabolism , Spermatozoa/physiology , Amino Acid Sequence , Animals , Cell Nucleus/ultrastructure , Circular Dichroism , Female , Fluorescence , Male , Molecular Sequence Data , Nephelometry and Turbidimetry , Nuclear Proteins/chemistry , Nuclear Proteins/isolation & purification , Nucleoplasmins , Ovum/chemistry , Phosphoproteins/chemistry , Phosphoproteins/isolation & purification , Protein Conformation , Salmine/metabolism , Salmon , Spectrophotometry/methods , Spectrophotometry, Ultraviolet , Spermatozoa/chemistry , Xenopus laevis
11.
J Immunol ; 158(12): 5698-706, 1997 Jun 15.
Article in English | MEDLINE | ID: mdl-9190919

ABSTRACT

It was found that freshly isolated BALB/c CD4+ T cells produced high levels of IL-4 and IL-10 in response to immobilized anti-CD3 mAb, while C57BL/6 CD4+ T cells produced low amounts of IL-4 and IL-10. The high IL-4-producing ability of BALB/c mice was demonstrated to be genetically dominant and it was controlled by non-MHC gene (or genes). The cells responsible for IL-4 production in BALB/c mice were defined as TCRVbeta8.2+ CD4+ CD62L- CD45RB- memory-type T cells, which were distinct from NK1.1+ CD4+ NKT cells. Although these memory-type T cells were also detected in C57BL/6 mouse spleen at the same frequency, they showed a functionally different property from BALB/c CD4+ CD62L- CD45RB- T cells in terms of IL-4 production. The fact that germfree BALB/c mouse spleen cells also produced high levels of IL-4 suggested that the IL-4 producer in BALB/c mice might be developed under the influence of unknown factors other than environmental Ags. The CD4+ CD62L- CD45RB- T cells obtained from BALB/c mice accelerated the development of IL-4-producing memory-type CD4+ T cells from CD4+ CD62L+ CD45RB+ naive T cells prepared from OVA-specific TCR-transgenic mice. Therefore, IL-4-producing CD4+ CD62L- CD45RB- T cells might play an important role in the preferential induction of Th2-dominant immunity in BALB/c mouse strain.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Interleukin-4/biosynthesis , Receptors, Antigen, T-Cell, alpha-beta/analysis , Th2 Cells/immunology , Animals , Immunologic Memory , L-Selectin/analysis , Leukocyte Common Antigens/analysis , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Spleen/immunology
12.
Biosci Biotechnol Biochem ; 61(12): 2151-2, 1997 Jan.
Article in English | MEDLINE | ID: mdl-27396896

ABSTRACT

Post-translational modification of core histones is essential in processes requiring chromatin remodeling. We report here a novel modification in histones of the sperm of the starfish, Asterina pectinifera, which involves an ε-(γ-glutamyl)lysine cross-link between the glutamine residue at position 9 of histone H2B and the lysine residue at position 12 of histone H4.

13.
Int Immunol ; 8(10): 1473-81, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8921426

ABSTRACT

In order to determine whether the cells immigrating into the thymus have been committed to the T cell lineage, we examined the gene expression of the TCR complex in fetal thymus (FT) and fetal liver (FL) precursors. We previously showed that c-kit bright-positive, Pgp-1 bright-positive and lineage markers negative fetal thymocytes (c-kit+ FT cells) are the most immature cells which do not undergo gene rearrangement of the TCR beta chain. In this study, we demonstrated that the gene rearrangement of TCR gamma as well as beta chains does not occur in c-kit+ FT cells, but that the germline transcript of their TCR beta was found in J-C regions. The TCR beta gene was demethylated in c-kit+ FT cells. CD3 gamma, delta and epsilon subunit genes were also expressed at the mRNA levels in c-kit+ FT cells, but cytoplasmic protein staining divided them into two populations: cytoplasmic CD3 epsilon positive and negative cells. These features were not observed in c-kit+ FL cells. Moreover, Ly-1 expression was found on c-kit+ FT cells but not on c-kit+ FL cells. These results indicate that DNA alteration on the TCR beta gene initiates with other phenotype expression determining the T cell lineage in the thymus prior to TCR gene rearrangement.


Subject(s)
CD3 Complex/analysis , DNA Methylation , Gene Rearrangement, T-Lymphocyte/immunology , Proto-Oncogene Proteins c-kit/analysis , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, alpha-beta/metabolism , T-Lymphocytes/immunology , Thymus Gland/immunology , Transcription, Genetic/genetics , Animals , CD3 Complex/biosynthesis , Cell Differentiation/immunology , Female , Mice , Mice, Inbred C57BL , Pregnancy , Proto-Oncogene Proteins c-kit/biosynthesis , T-Lymphocytes/metabolism , Thymus Gland/cytology
14.
Int Immunol ; 8(10): 1529-35, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8921432

ABSTRACT

Immature CD4+CD8+ double-positive (DP) thymocytes are positively selected for further development if they express TCR reacting with thymic ligands of low affinity. However, the majority of DP thymocytes express low TCR levels. This low level of TCR may be insufficient to recognize thymic ligands. To understand the basis for the low expression of TCR on DP thymocytes, we determined the density of TCR expression at various stages of their development using TCR transgenic (TCR-Tg) mice. We found that TCR expression was high in the thymocytes that had recently transited into the DP stage but then gradually decreased on DP cells if they were not selected by TCR interaction with MHC molecules. However, such TCR suppression was not observed in positively selected DP cells and in the non-selected DP cells obtained from CD45 deficient mice or from mice receiving anti-CD4 mAb. These findings suggest that the once highly expressed TCR at the DP stage is suppressed by CD45 and/or CD4 on non-selected thymocytes. Furthermore, TCR suppression is prevented by TCR-mediated signals. The maintenance of high TCR levels on positively selected DP thymocytes may facilitate their selection.


Subject(s)
CD4 Antigens/pharmacology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Down-Regulation/immunology , Leukocyte Common Antigens/pharmacology , Receptors, Antigen, T-Cell, alpha-beta/biosynthesis , Receptors, Antigen, T-Cell, alpha-beta/drug effects , Thymus Gland/metabolism , Animals , CD4 Antigens/immunology , Cell Differentiation/immunology , Crosses, Genetic , Leukocyte Common Antigens/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Transgenic , Receptors, Antigen, T-Cell, alpha-beta/genetics , Thymus Gland/cytology
16.
Brain Behav Immun ; 10(1): 17-26, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8735566

ABSTRACT

Haloperidol (HPD) is a dopamine receptor blocker and a major causative agent of neuroleptic malignant syndrome. To investigate the influence of HPD on immune responsiveness, the natural killer (NK) cell activity of mice was examined after intraperitoneal administration of HPD for 5 days. NK cell activity was markedly decreased without a depletion of NK cells. Bromocriptine (BROMO), which is used for the treatment of neuroleptic malignant syndrome, also decreased NK cell activity. The suppressive effect on NK cell activity was inhibited by injecting both HPD and BROMO simultaneously. Serum levels of prolactin (PRL) decreased after BROMO injection, although serum PRL level was not decreased after the combined administration of HPD and BROMO agents. The reduction of NK cell activity caused by BROMO and by HPD was prevented by the co-injection of PRL and by a beta-adrenergic blocker, respectively. These results indicate that HPD decreases NK cell activity in a PRL-independent manner and that BROMO decreases it via PRL reduction. It seems that the PRL-independent suppressive effect of HPD on NK cells, which is neutralized by BROMO, is mediated by splenic sympathetic function via the beta-adrenergic receptor system. Therefore, BROMO helps to alleviate the depressed NK cell activity caused by HPD therapy.


Subject(s)
Antiparkinson Agents/pharmacology , Antipsychotic Agents/pharmacology , Bromocriptine/pharmacology , Haloperidol/pharmacology , Killer Cells, Natural/drug effects , Adrenergic beta-Antagonists/pharmacology , Animals , Chromium , Flow Cytometry , Lymphocyte Count , Mice , Mice, Inbred C57BL , Prolactin/blood , Prolactin/pharmacology , Spleen/cytology , Spleen/drug effects , T-Lymphocytes/drug effects
17.
Opt Lett ; 21(12): 887-9, 1996 Jun 15.
Article in English | MEDLINE | ID: mdl-19876192

ABSTRACT

Projected specklegrams are used for spectroscopy with high spatial resolution under atmospheric turbulence. One-dimensional peak tracking allows one to realize high throughput and simple real-time operation for speckle spectroscopy. Results of simulation experiments are presented, and they confirm the usefulness of the proposed method.

18.
Opt Lett ; 20(14): 1574-6, 1995 Jul 15.
Article in English | MEDLINE | ID: mdl-19862087

ABSTRACT

A stellar speckle spectrometer with tip-tilt operation is proposed for high-spatial-resolution spectroscopy under atmospheric turbulence. A specklegram is used to drive a tip-tilt mirror for real-time shift-and-add operation to its dispersed specklegram. The proposed speckle spectroscopy attains a long exposure for the spectrum and a slit spectrometer. Several simulation experiments confirm the effectiveness of our method.

19.
Int Immunol ; 6(9): 1451-4, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7819155

ABSTRACT

The effects of IL-7 on the growth and differentiation of thymocytes were analyzed using murine fetal thymus organ cultures (FTOC) in the presence of mAbs specific for the conventional IL-7 receptor (IL-7R) and for the common gamma (gamma c) chain. In FTOC, the development of CD4-CD8- double-negative thymocytes to CD4+CD8+ double-positive (DP) and CD4+ or CD8+ single-positive (SP) cells was not completely blocked by adding these mAbs, although cell growth was reduced by the treatment. To define a developing stage sensitive to the mAbs, most immature thymocytes, Pgp-1+ c-kit+ cells, were cultured in 2-deoxyguanosine treated fetal thymus. In the presence of both mAbs in the culture, neither DP nor SP thymocytes developed whereas either of the mAbs partially blocked their development. These results indicate that the gamma c chain is involved in early T cell development as an indispensable subunit of the functional IL-7 receptor complex.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Receptors, Interleukin/immunology , Thymus Gland/cytology , Animals , Antibodies, Monoclonal/immunology , Cell Differentiation , Fetus , Flow Cytometry , Interleukin-7/immunology , Lymphocyte Activation , Mice , Mice, Inbred C3H , Receptors, Interleukin-7 , Thymus Gland/drug effects , Thymus Gland/embryology
20.
Eur J Immunol ; 24(6): 1339-44, 1994 Jun.
Article in English | MEDLINE | ID: mdl-7515811

ABSTRACT

Ten percent of 15-day fetal thymocytes of mice were Pgp-1+Thy-1lo cells. Half were strongly stained with monoclonal antibodies (mAb) recognizing the oncogene product, c-kit, but were not stained with mAb against non-T cell markers such as B220, Mac-1 and Gr-1. The isolated Pgp-1+c-kit+ thymocytes showed no rearranged bands for V-DJ and D-J of T cell receptor (TcR) beta, but Pgp-1(-)-c-kit- thymocytes showed D-J rearranged bands. Both cells expressed the RAG-2 gene which is required for the V(D)J recombination process. When Pgp-1+c-kit+ thymocytes were cultured in 2-deoxyguanosine-treated alymphocytic fetal thymus, they became TcR-expressing mature type T cells, but this differentiation was reduced by the addition of anti c-kit mAb. These data indicate that Pgp-1+c-kit+ thymocytes are pro-T cells with the potential to differentiate mature T cells in the thymic environment. This study also indicates that c-kit-mediated signals promote the differentiation of thymocytes during their early stages.


Subject(s)
DNA-Binding Proteins , Gene Rearrangement, beta-Chain T-Cell Antigen Receptor , Protein Biosynthesis , Proto-Oncogene Proteins/biosynthesis , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptors, Colony-Stimulating Factor/biosynthesis , T-Lymphocytes/metabolism , Thymus Gland/embryology , Animals , Base Sequence , Cell Differentiation , Flow Cytometry , Mice , Mice, Inbred C3H , Molecular Sequence Data , Organ Culture Techniques , Polymerase Chain Reaction , Proto-Oncogene Proteins c-kit , Thymus Gland/cytology , Thymus Gland/metabolism
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