Biomedical subjects

S Ju

Publications and source records attributed to S Ju.

9 recordsLinked to original sources

PubMed2004

Characterization and functional study of five novel monoclonal antibodies against human OX40L highlight reverse signalling: enhancement of IgG production of B cells and promotion of maturation of DCs.

OX40 ligand (OX40L), a molecule originally identified as human gp34, is an important co-stimulatory molecule during immune response. In this study, we report on five functional mouse anti-human OX40L monoclonal antibodies named as 9H10, 4C12, 8D10, 4H4 and 1G1, characterized by means of flow cytometry, Western blot and competition assay. These monoclonal antibodies bound to distinct OX40L epitopes on activated B cells and dendritic cells (DCs) and two of them could suppress the proliferation of T lymphocytes co-stimulated by mature DCs. Furthermore, we demonstrated that our monoclonal antibodies, such as 9H10 and 4C12, could trigger OX40L reverse signal that enhanced IgG production of B cells and promoted maturation of DCs as evidenced by the upexpression of CD80, CD86, CD83 and CXCR4 and monoclonal antibody 9H10 could also promote anti-CD40 monoclonal-antibody-stimulated DCs in order to induce T cells to secrete more interleukin-2 and interferon-gamma, which suggested that OX40L signals could strengthen the effect of CD40 signals on promoting Th1 differentiation.

Animals↗

PubMed2002

Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase.

Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated that the behavioral effects of epi-inositol may be due to its effects on gene expression. Yeast INO1expression was measured in northern blots. INM1 was determined by beta-galactosidase activity in a strain containing the fusion gene INM1-lacZintegrated into the genome. Epi-inositol affects regulation of expression of the INO1 gene (encoding inositol-1-P synthase), even though it cannot support growth of an inositol auxotroph (suggesting that, as in mammalian cells, it is not incorporated into phosphatidylinositol). Like myo-inositol, although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium- or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol. The observed regulatory effects of epi-inositol on expression of the most highly regulated gene in the inositol biosynthetic pathway may help to explain how this inositol isomer can exert behavioral effects without being incorporated into phosphatidylinositol.

Anticonvulsants↗

PubMed1998

[Curative effect of TCM-WM therapy on Wilson disease with different clinical phenotypes and polymorphisms of ATP7B gene].

OBJECTIVE: To investigate the curative effect of TCM-WM therapy on Wilson disease (WD) with different clinical phenotypes and polymorphisms of ATP7B gene. METHODS: One hundred and twenty-two WD patients with different clinical phenotypes were treated with unithiol 20 mg/kg per day and Gandou tablet ([symbol: see text]) for 1 month. Exon 18 of ATP7B gene extracted from patients and 20 healthy volunteers were amplified with PCR technique, mutations and polymorphisms were screened by SSCP analysis. RESULTS: Four kinds of abnormal migration bands in PCR-SSCP were seen in 37 patients, mutation frequencies of three different clinical phenotypes and curative effect between mutation and non-mutation patients did not show any significant difference, P > 0.05. But total effective rate of patients with Wilson type or pseudosclerosis type was significantly higher than that of patients with hepatic type, P < 0.05. CONCLUSIONS: The exon 18 of ATP7B gene of Chinese WD patients may be one of the regions with higher mutation frequency, most of them are compound heterozygotes and patients with different clinical phenotypes have different response to TCM-WM therapy. It indicate that specific mutations at least in part play a role in influencing clinical phenotypes and curative effect.

Adenosine Triphosphatases↗

PubMed1997

[9-cis retinoic acid induces apoptosis in HL-60 cells].

OBJECTIVE: To investigate the apoptosis of HL-60 cells induced by 9-cis retinoic acid (9-cis RA), and illustrate the possible molecular mechanism. METHODS: Apoptosis was detected by morphological observation, DNA electrophoresis and flow cytometric cell cycle analysis. Bcl-2 expression was detected by flow cytometry. RESULTS: 9-cis RA initiated apoptosis of HL-60 cells after inducing them irreversibly commited to differentiation. Bcl-2 was downregulated during the differentiation and apoptosis process. 9-cis RA was more potent than all-trans retinoic acid (ATRA) did in inducing terminal differentiation associated apoptosis and in downregulation of Bcl-2 expression. CONCLUSION: 9-cis RA can induce apoptosis in HL-60 cells. Downregulation of Bcl-2 expression appears to play an important role in the apoptosis of the differentiated leukemic cells.

Alitretinoin↗

PubMed1996

Fas modulation of apoptosis during negative selection of thymocytes.

A major mechanism maintaining immune tolerance is the deletion of potentially autoreactive thymocytes by apoptosis during development in the thymus. Previous reports suggest that apoptosis is induced by high avidity signals transduced via the T cell receptor; however, the role of signals transduced by other cell surface receptors during thymic selection remains poorly understood. Fas, a member of the TNF receptor family, has been shown to induce apoptosis in mature peripheral T cells; however, the effects of Fas on negative selection of thymocytes have not been previously detected. Using a sensitive terminal deoxynucleotidyl transferase method to detect apoptotic cells, we found that mutant Fas molecules in lpr mice decrease the sensitivity of thymocytes to T cell receptor-mediated apoptosis and that blockade of Fas-Fas ligand interactions in vivo can inhibit antigen-induced apoptosis of thymocytes in non-lpr mice. Thus, we have shown that Fas, in conjunction with antigen-specific signals, can modulate apoptosis during negative selection of thymocytes.

Amino Acid Sequence↗

PubMed1995

A neuron model based on brain biochemical principles.

The electrical activity and excitation of the brain is based on certain biochemical processes, particularly, the activity of transmitter-receptor-ion channel system and the DNA-RNA-Pr (Pr:protein) system. There have already been some neuron models relating to the ion channel, but the kinds and numbers of transmitters, receptors, and ion channels are directly or indirectly conditioned by the DNA-RNA-Pr system. To reflect these facts, we present a new neuron model based on the important biochemical chains of the brain. This model is applied to both the simulation research of electrical activity and the information processing function of the brain. In this demonstration, we will introduce: 1) How to express the connection between the neuron excitation and the transmitter-receptor-ion channel system; 2) How to express the connection between the transmitter-receptor-ion channel system of neuron and the DNA-RNA-Pr system; 3) How to express the connection among 16,000 artificial neurons on the basis of the above-mentioned points; 4) The time and the state of the excitation passing through a particular neuron in a group of neurons.

Brain↗

PubMed1985

Functional analysis of macrophage hybridomas. I. Production and initial characterization.

A series of macrophage hybridomas were generated by fusion of splenic adherent cells with P388D1 tumor cells. Forty-two cell lines were established, and each was cloned by limiting dilution. Six clones that exemplified the spectrum of macrophage heterogeneity were selected for further analysis. Qualitative and quantitative differences in phenotype and functional activity were noted. Some clones constitutively expressed Ia antigens, whereas others only expressed detectable levels of Ia after lymphokine activation. The level of antigen-presenting activity generally correlated with the level of Ia expression. Furthermore, interclonal differences were noted in the levels of receptor-mediated phagocytosis and IL 1 secretion. Generally, the hybridoma clones maintained stable phenotypic and functional properties during approximately 1 yr of continuous in vitro culture. These cloned hybridoma cell lines represent a useful resource to analyze macrophage biology and to dissect structure and function relationships.

Animals↗

PubMed1977

Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype.

Inoculation of rabbit anti-idiotypic (anti-id) antibodies suppresses the subsequent appearance of a cross-reactive idiotype (CRI) associated with the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. Such suppressed mice produce normal concentrations of anti-Ar antibodies which lack the CRI, but against which anti-id antisera can be prepared. The anti-Ar antibodies of an individual, suppressed mouse do not in general share idiotype with anti-Ar antibodies of other A/J mice, either suppressed or nonsuppressed. The present experiments were undertaken to quantitate several "private idiotypes" in a large number of hyperimmunized A/J mice. Anti-Ar antibodies of three mice, suppressed for the CRI, were labeled with 125I and subjected to isoelectric focusing. Four single peaks, that were over 90% reactive with autologous antiid, were randomly selected for use as ligands in a radioimmunoassay, and ascitic fluids containing anti-Ar antibodies from 181 A/J mice were tested as inhibitors. Two of the four idiotypes could not be detected in any mouse other than the donor. The concentration of the idiotype was less than 1 part in 1,250 to less than 1 part in 25,000 of the anti-Ar antibody population; these are minimum values. A third idiotype was detected in 3 of the 181 mice, but at very low concentrations. The fourth idiotype was present in 28% of the mice, again at a low concentration. The data support the existence of a very large repertoire of anti-Ar antibodies in the A/J strain and are consistent with a process of random somatic mutation for generating diversity in hypervariable regions. It is proposed that the cross-reactive idiotype may be controlled by a germ line gene or a gene related to a germ line gene through a small number of somatic mutations; and that the idiotypes that were not detectable in other mice were the products of genes that had undergone extensive mutations, with a low probability of recurrence in other mice.

Animals↗

PubMedDate not supplied

Studies of a cross-reactive idiotype associated with anti-para-azophenylarsonate antibodies of A/J mice.

We have reviewed studies of a cross-reactive idiotype (CRI), associated with anti-para-azophenylarsonate (anti-Ar) antibodies of A/J mice, and have presented some recent data. H chains from molecules with the CRI are homogeneous through the first hypervariable region whereas L chains show heterogeneity in the first framework segment. The constancy of N-terminal H chain sequences from 10 individual mice indicates that the framework is encoded by a germ-line gene, and that mutations have little effect on the observed framework sequence. H chains lacking the CRI show great heterogeneity in the first hypervariable segment, indicating a direct relationship between sequence and idiotype. Adult A/J mice can be suppressed with respect to the production of the CRI by administration of rabbit antiidiotypic antibody. When immunized, such mice produce anti-Ar antibodies with "private" idiotypes present at extremely low concentrations, or absent, in anti-Ar antibodies of other A/J mice. These private idiotypes can be transferred adoptively to mildly irradiated (200 r) syngeneic recipients with lymphoid cells, and serial transfers can be carried out after immunization. The original CRI remains suppressed. This presents the possibility of structural studies of anti-Ar antibodies varying in idiotype from a single strain. The work should also provide information on the degree of diversity of anti-Ar antibodies within the strain.

Amino Acid Sequence↗