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Biomedical subjects

T Honjo

Publications and source records attributed to T Honjo.

At least 37 records · Page 2Linked to original sources
PubMed2001

Extraction of iridium (IV) from hydrochloric acid media with crown ether in chloroform, and its determination by ICP-AES.

A new method for the quantitative extraction and determination of trace amounts of iridium from hydrochloric acid media has been established based on the formation of an ion-association complex of iridium hexachloro anion IrCl6(2-) with dicyclohexyl-18-crown-6 (DC18C6) oxonium cation in chloroform, then determination by inductively coupled plasma atomic emission spectrometry (ICP-AES). The effect of various factors (solvent, acid concentration, crown ether, reagent concentration, shaking time, composition of the extracted species, foreign ions, etc.) on the extraction and back-extraction of iridium has been investigated. The procedure was used to determine traces of iridium in palladium chloride and rhodium chloride.

Journal Article↗
PubMed2001

Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate.

Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells.

Animals↗
PubMed2001

Human genetic defects in class-switch recombination (hyper-IgM syndromes).

Several genetic defects in class-switch recombination, leading to hyper-IgM syndromes, have been recently described in humans. Besides the well-known role of interaction between CD40-ligand and CD40, these pathological conditions definitively demonstrate the requirement of CD40-mediated NF-kappaB activation and the essential role of a newly described molecule, activation-induced cytidine deaminase (AID), in B cell terminal differentiation.

Animals↗
PubMed2001

The IL-7 receptor controls the accessibility of the TCRgamma locus by Stat5 and histone acetylation.

The IL-7 receptor (IL-7R) plays critical roles in expansion and V(D)J recombination during lymphocyte development. Here we demonstrate that cytokine stimulation rapidly recruits Stat5 and transcriptional coactivators to the Jgamma germline promoter and induces histone acetylation, germline transcription, and accessibility in Ba/F3 cells. We also show that histone acetylation of the TCRgamma locus is significantly reduced in IL-7R-deficient thymocytes and that the introduction of active Stat5 restores the histone acetylation and accessibility of the locus. Furthermore, treatment with histone deacetylase inhibitor recovers the histone acetylation and accessibility in IL-7R-deficient thymocytes. Therefore, these results suggest that Stat5 may recruit the transcriptional coactivators to the Jgamma germline promoter and control the accessibility of the TCRgamma locus by histone acetylation.

Acetylation↗
PubMed2001

PD-1: an inhibitory immunoreceptor involved in peripheral tolerance.

PD-1 deficiency causes a variety of autoimmune diseases. Inhibitory signaling through the PD-1 receptor might therefore be involved in the regulation of peripheral tolerance. The constitutive expression of PD-1 ligands (PD-L1 and PD-L2) on parenchymal cells of heart, lung and kidney suggests that the PD-1-PD-L system could provide unique negative signaling to help prevent autoimmune diseases.

Animals↗
PubMed2001

A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interference contrast microscopy.

Osteocytes are the most numerous cells in bone, embedded within the mineralized bone matrix. Their slender cytoplasmic processes form a complex intercellular network. In addition, these processes are thought to be important structures in the response to mechanical stress. This study provides an extensive analysis of the three-dimensional structure of the osteocyte and its processes in 16-day-old embryonic chick calvariae, based on nondestructive subsurface histotomography using both confocal laser scanning (CLS) microscopy and differential interference contrast (DIC) microscopy. OB7.3, a chicken osteocyte-specific monoclonal antibody, and Texas Red-X-conjugated phalloidin were used to confirm the osteocyte phenotype and to identify whole cells in the calvariae, respectively. Serial CLS images revealed morphological changes in bone cells up to 20 microm in depth. Osteocytes had widely spread their processes into the osteoblast layer, and we found for the first time that some of these processes had elongated to the vascular-facing surface of the osteoblast layer. Furthermore, stereotype images reconstructed from CLS images could show the three-dimensional distribution of these processes. Using the stereopair image, we could evaluate the frequency of processes between osteocytes and osteoblasts. Complementation of DIC microscopy revealed canaliculi and lacunae with high contrast. The distributional pattern of canaliculi generally coincided with that of the osteocyte processes. We consider that the combination method of CLS microscopy and DIC microscopy using a laser scanning microscope is a very useful new technical approach for investigating osteocytes in bone.

Animals↗
PubMed2001

Linking class-switch recombination with somatic hypermutation.

The recent discovery of a molecular link between two apparently different genetic alteration events--class-switch recombination and somatic hypermutation--has led to the idea that the recognition and cleavage of target DNA in these two events might be mediated by similar or identical molecules to those involved in RNA editing. This could mean that the complexity of mammalian genetic information may be enriched by an interplay between RNA editing and DNA modification.

APOBEC-1 Deaminase↗
PubMed2001

PD-L2 is a second ligand for PD-1 and inhibits T cell activation.

Programmed death I (PD-I)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4+ T cells. At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals. In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G0/G1 but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone. PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines. Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulatingT cell responses.

Amino Acid Sequence↗
PubMed2001

Effects of photocatalytic reactions on marine plankton: titanium dioxide powder as catalyst on the body surface.

Photocatalytic effects of TiO2 powder on marine plankton were examined by the use of either brine shrimp Artemia salina or noxious red tide flagellate Chattonella antiqua as a probe. After UV (365 nm) irradiation for ca. 1 hour, A. salina stopped moving and the body surface was completely covered by TiO2 powder. Similar photoirradiation of C. antiqua, on the other hand, induced deformation of the body from spindle to round shape within 20 minutes. The deformed C. antiqua recovered to normal shapes, when the cells were kept in the same conditions but without UV irradiation for more than 40 minutes. On the prolonged UV irradiation (more than 100 minutes), however, the cells burst and came to annihilation. The photocatalytic reactions of TiO2 on the body surface are thus concluded to induce fatal damages to these microorganisms.

Animals↗
PubMed2001

Palindromic but not G-rich sequences are targets of class switch recombination.

In order to understand the specificity of sequences or structures recognized by a recombinase involved in class switch recombination (CSR), we examined the relative CSR efficiency of various switch sequences in artificial CSR constructs that undergo CSR in CH12F3-2 murine B lymphoma line. Since CSR recombination is not specific to switch regions of different isotypes or orientation of S sequences, we examined the efficiency of S sequences of non-mammalian species and artificial sequences which lack several characters of mammal switch sequences: chicken S(mu), Xenopus S(mu), telomere, multiple cloning site (MCS) and unrelated negative control sequence. CSR occurred in chicken S(mu) and MCS with significantly higher efficiency than the negative control. A common character of these two sequences is that they are rich in palindrome and stem-loop structures. However, telomeres, which are G-rich and repetitive but not palindromic, could not serve as switch sequences at all. The AT-rich Xenopus S(mu) sequence was inefficient but capable of CSR. CSR breakpoint distribution suggests that the cleavage may take place preferentially in the proximity of the junctions (neck) between the loop and stem in the secondary structure of the single-stranded S sequence, which can be formed by palindromic sequences. The results suggest that the secondary structure of S-region sequences which is transiently formed during transcription may be necessary for recognition by class switch recombinase.

Animals↗
PubMed2001

Life-cycle toxicity of 4-nonylphenol to medaka (Oryzias latipes).

We studied the chronic effects of 4-nonylphenol (4-NP) on reproductive status of medaka (Oryzias latipes) over two generations of continuous exposure. The exposure study of the parental (F0) medaka was begun on embryos within 24 h postfertilization and continued with monitoring through embryological development, hatching, posthatch survival, growth, sexual differentiation, and reproduction under flow-through exposures to mean measured 4-NP concentrations of 4.2, 8.2, 17.7, 51.5, and 183 microg/L for up to 104 d. Eggs spawned from the F0 fish at 102 and 103 d posthatch were also examined for hatchability, survival after hatching, growth, and sexual differentiation until 60 d posthatch. The 183-microg/L treatment significantly reduced the embryo survival and swim-up success of the F0 fish. The cumulative mortality after swim-up of the F0 fish exposed to 17.7 and 51.5 microg/L were significantly higher than the control mortality. No concentration-related effect of 4-NP was observed on the growth of surviving F0 fish at 60 d posthatch. However, the sex ratio estimated from the appearance of their secondary sex characteristics was skewed toward female in the 51.5-microg/L treatment. Additionally, gonadal histology showed that 20% of the fish in the 17.7-microg/L treatment and 40% in the 51.5-microg/L treatment had testis-ova, indicating that 4-NP affects the gonadal development and survival of medaka at similar concentrations in juveniles. The sex ratio of the F0 fish in the 51.5-microg/L treatment was completely skewed toward female; subsequently, the effects on fecundity and fertility in this generation were monitored at mean measured concentrations of 4.2, 8.2, and 17.7 microg/L from 71 to 103 d posthatch. Fecundity was unaffected by any of the treatments examined. The mean fertility in the 17.7-microg/L treatment was reduced to 76% of that in the controls, although no statistically significant differences were determined. Overall, these results indicate that the lowest-observed-effect concentration (LOEC) and no-observed-effect concentration (NOEC) of 4-NP through the life cycle of the F0 medaka were 17.7 and 8.2 microg/L, respectively. In the F1 medaka, no significant effects were observed on hatching success, posthatch mortality, or growth, but sexual differentiation at 60 d posthatch was affected. Induction of testis-ova in the gonads of the F1 fish was observed in both the 8.2- and the 17.7-microg/L concentrations. The results indicate that 4-NP can have significant effects on reproductive potential of medaka at concentrations as low as 17.7 microg/L.

Animals↗
PubMed2000

Migration and differentiation of autoreactive B-1 cells induced by activated gamma/delta T cells in antierythrocyte immunoglobulin transgenic mice.

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-secreting cells. However, little is known about the process of B-1 cell migration and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-gamma/delta Tg mice specific for a self-thymus leukemia (TL) antigen in the recombination activating gene (RAG)2(-/-) background. In the presence of the self-antigen, Tg gamma/delta T cells increased in number and manifested activated phenotypes. Peritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoimmune hemolytic anemia. Furthermore, transfer of RAG2(-/-) x HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2(-/-) x TCR-gamma/delta Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates that the migration of B-1 cells and differentiation into the antibody-secreting cells can be induced by noncognate T cell help and implies the possibility that gamma/delta T cells may induce B-1 cell differentiation in vivo.

Anemia↗
PubMed2000

T-Independent immune response: new aspects of B cell biology.

Recent results emphasize the roles of T-independent antibody response in humoral defenses, for which B1 cells and marginal zone B cells are mostly responsible. We discuss how these cells are activated, migrate, and differentiate into antibody-producing cells in various lymphoid tissues. Based on recent findings in each of these areas of B cell biology, we propose a possible mechanism for peripheral tolerance of autoreactive B cells at target organs.

Animals↗
PubMed2000

Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.

PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.

Amino Acid Sequence↗
PubMed2000

Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme.

Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before or after immunization. AID-/- spleen cells stimulated in vitro with LPS and cytokines failed to undergo class switch recombination although they expressed germline transcripts. Immunization of AID-/- chimera with 4-hydroxy-3-nitrophenylacetyl (NP) chicken gamma-globulin induced neither accumulation of mutations in the NP-specific variable region gene nor class switching. These results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation.

APOBEC-1 Deaminase↗
PubMed2000

Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).

The activation-induced cytidine deaminase (AID) gene, specifically expressed in germinal center B cells in mice, is a member of the cytidine deaminase family. We herein report mutations in the human counterpart of AID in patients with the autosomal recessive form of hyper-IgM syndrome (HIGM2). Three major abnormalities characterize AID deficiency: (1) the absence of immunoglobulin class switch recombination, (2) the lack of immunoglobulin somatic hypermutations, and (3) lymph node hyperplasia caused by the presence of giant germinal centers. The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.

APOBEC-1 Deaminase↗
PubMed2000

Netrin-G1: a novel glycosyl phosphatidylinositol-linked mammalian netrin that is functionally divergent from classical netrins.

UNC-6/netrins compose a small phylogenetically conserved family of proteins that act as axon guidance cues. With a signal sequence trap method, we isolated a cDNA encoding a novel member of the UNC-6/netrin family, which we named netrin-G1. Unlike classical netrins, netrin-G1 consists of at least six isoforms of which five were predominantly anchored to the plasma membrane via glycosyl phosphatidyl-inositol linkages. Netrin-G1 transcripts were first detected in midbrain and hindbrain regions by embryonic day 12 and reached highest levels at perinatal stages in various brain regions, including olfactory bulb mitral cells, thalamus, and deep cerebellar nuclei. Its expression was primarily restricted to the CNS. Interestingly, netrin-G1 proteins did not show appreciable affinity to any netrin receptor examined. Unlike netrin-1, a secreted form of netrin-G1 consistently failed to attract circumferentially growing axons from the cerebellar plate. Our findings suggest that netrin-G1 and its putative receptors have coevolved independently from the classical netrins. The expression pattern of netrin-G1 and its predicted neuronal membrane localization suggest it may also have novel signaling functions in nervous system development.

Amino Acid Sequence↗