Search PubMed⌕ Search

Biomedical subjects

J Tseng

Publications and source records attributed to J Tseng.

At least 37 records · Page 2Linked to original sources
PubMed1998

STCP-1 (MDC) CC chemokine acts specifically on chronically activated Th2 lymphocytes and is produced by monocytes on stimulation with Th2 cytokines IL-4 and IL-13.

STCP-1 stimulated T cell chemoattractant protein-1 (STCP-1) (macrophage-derived chemokine; MDC), a recently described CC chemokine for chronically activated T lymphocytes, was found to act specifically on a subset of memory CD4 lymphocytes that displayed a Th2 cytokine profile. Also, STCP-1, thymus and activation regulated chemokine (TARC), eotaxin, and eotaxin-2 acted specifically on in vitro derived Th2 lymphocytes, while IP-10 (IFN-gamma-inducible 10-kDa protein) showed some preference for Th1 lymphocytes. The corresponding receptors for eotaxin, TARC, and IP-10 are also differentially expressed on Th1 and Th2 lymphocytes. In desensitization Ca flux experiments, TARC and STCP-1 bound to a common receptor and therefore at least one chemokine receptor for STCP-1 is CCR4. STCP-1 expression is restricted to immune cells. Dendritic cells, B cells, and macrophages produce STCP-1 constitutively, while NK cells, monocytes, and CD4 lymphocytes produce STCP-1 upon appropriate stimulation. Production of STCP-1 is positively modulated by Th2 cytokines IL-4 and IL-13 but inhibited by IL-10.

Animals↗
PubMed1998

Human keratinocyte growth factor recombinantly expressed in Chinese hamster ovary cells: isolation of isoforms and characterization of post-translational modifications.

Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that acts specifically on epithelial cells in a paracrine mode. We employed a mammalian expression system to synthesize recombinant human KGF and isolated two preparations, KGF-a and KGF-b, from medium conditioned by Chinese hamster ovary cells. On an SDS-PAGE gel, KGF-a migrates as two bands near 25-29 kDa and contains both N- and O-linked sugar moieties attached near the N-terminus. Detailed structural characterization confirms that KGF-a contains a single amino acid sequence predicted from cDNA sequence and the molecule has two intramolecular disulfide bridges, Cys1-Cys15 and Cys102-Cys106. An additional Cys at position 40 is free and resides in a solvent-inaccessible environment. Mass spectrometric analyses of KGF-a peptides verify the occurrence of several post-translational modifications in the molecule, including partial oxidation at Met28, partial sulfation at Tyr27, and glycosylation at Asn14 and Thr22. The Asn-linked carbohydrate structures are heterogeneous, which include biantennary, triantennary, and tetraantennary structures with none or up to four sialic acids attached to various structures, while the Thr-linked carbohydrates contain typical mucin-type structures. KGF-b is an N-terminally truncated form of KGF-a posttranslationally processed at Arg23 and is not glycosylated. Both KGF-a and KGF-b forms are capable of stimulating DNA synthesis in quiescent Balb/MK mouse epidermal keratinocytes.

Amidohydrolases↗
PubMed1997

B-cell antigen receptor-induced apoptosis requires both Ig alpha and Ig beta.

The response of a B cell to antigen is dependent on the surface expression of a clonotypic B-cell receptor complex (BCR) consisting of membrane-bound Ig and disulfide-linked heterodimers of Ig alpha/beta. Studies of Ig alpha or Ig beta have shown that the immunoreceptor tyrosine-based activation motif (ITAM) found in each cytoplasmic tail is capable of inducing most receptor signaling events. However, Ig alpha, Ig beta, and most of the other receptor chains that contain ITAMs, including CD3 epsilon, CD3 gamma, TCR zeta, and Fc epsilon Rl gamma, are found as components of multimeric and heterogeneous complexes. In such a complex it is possible that cooperativity between individual chains imparts functional capacities to the intact receptor that are not predicted from the properties of its constituents. Therefore, we developed a novel system in which we could form and then aggregate dimers, representative of partial receptor complexes, which contained either Ig alpha alone, Ig beta alone, or the two chains together and then examine their ability to induce apoptosis in the immature B-cell line, WEHI-231. Here we present evidence that heterodimers of Ig alpha and Ig beta efficiently induced apoptosis while homodimers of either chain did not. Apoptosis was associated with the inductive tyrosine phosphorylation of a very restricted set of proteins including the tyrosine kinase Syk. These findings may provide insight into the mechanisms by which the BCR, and other such multimeric receptor complexes, initiate both apoptotic and proliferative responses to antigen.

Antigens, CD↗
PubMed1997

Immediate responses of leukocytes, cytokines and glucocorticoid hormones in the blood circulation of monkeys following challenge with aerosolized staphylococcal enterotoxin B.

The immediate responses to aerosolized staphylococcal enterotoxin B (SEB) in respiratory toxic shock were studied in the circulation of rhesus monkeys with low antibody levels following immunization with SEB toxoid-containing microspheres. Both the surviving and dying monkeys had toxic shock syndrome 4-48 h after SEB challenge and all showed three distinctive patterns of immediate responses. The first pattern, characterized by the responses of all T cells, HLA-DRlo cells, monocytes, IL-2R+ cells, IFN-gamma, and augmented lymphocyte mitotic responses to lipopolysaccharide (LPS) and SEB in culture, was a rapid increase at 20 min followed by a quick decrease at 90 min to approximately the original levels. The second pattern, which included responses of HLA-DRhi cells, NK cells, adrenocorticotropic hormone (ACTH) and cortisol, was characterized by a moderate decrease at 20 min and a further decrease at 90 min. The third pattern, the inverse of the second pattern, including responses of polymorphonuclear leukocytes (PMN), concanavalin A (Con A) mitogenesis, IL-6 and IL-2, was a moderate increase at 20 min and a further increase at 90 min. Between the surviving and dying monkeys, the responses of T cells, HLA-DRhi cells, PMN and cortisol did not differ significantly, suggesting that they are the basic causes that initiated toxic shock. However, significant differences were seen in the responses of HLA-DRlo cells, monocytes, IL-2R+ cells and lymphocyte mitogenesis in culture at 20 min, and of Con A mitogenesis, NK cells, IL-2, IL-6 and ACTH at 90 min. These different responses are apparently the exacerbating causes of death of the monkeys. All together, the immediate responses seem to be caused by the combined effects of SEB superantigenicity, activation of NK cells and non-lymphoid cells, and depression of the neuroimmune defense system.

Adrenocorticotropic Hormone↗
PubMed1997

Dehydroepiandrosterone induces the transforming growth factor-beta production by murine macrophages.

Dehydroepiandrosterone(DHEA), a predominant androgen secreted by the adrenal cortex, and dehydroepiandrosterone sulfate (DHEAS). Its predominant form in serum, were investigated for their role in the regulation of transforming growth factor-beta (TGF beta) production by murine macrophages. Using a bioassay based on the growing inhibition to Mv-1-Lu cells and RT-PCR analysis, the effect of DHEA and DHEAS on the TGF-beta production and gene expression was studied. Results suggested that DHEA at relatively high concentration (10 microM) significantly induced TGF-beta secretion by both peritoneal cells and P388D1 macrophage-like cells. For the cells treated with DHEAS, no significant increase in TGF-beta secretion was found statistically. Result of RT-PCR confirmed the observation that cDNA from the cells pretreated with DHEA generated a significant amount of amplicons but cDNA samples obtained from both control cells and DHEAS-treated cells showed relatively weak signals. In a quantitative RT-PCR analysis, both DHEAS-treated cells and control cells failed to compete with internal standards and failed to produce any detectable amplicons. Dexamethasone, one of the commonly used glucocorticoids, induced an increase in TGF-beta secretion and in mRNA level. Dexamethasone and DHEA failed to show a synergistic effect on the DHEA-induced increase in TGF-beta secretion and gene expression. The biological significance for DHEA to act as a positive stimulator for TGF-beta production and its role in glucocorticoid-mediated immunoregulation needs to be further delineated.

Animals↗
PubMed1996

ErbB receptor activation, cell morphology changes, and apoptosis induced by anti-Her2 monoclonal antibodies.

A panel of mAbs were generated against the purified soluble form of erbB2/Her2 receptor, corresponding to the extracellular region of the receptor, and examined for their ability to mimic the receptor ligand. Some of the mAbs strongly induced tyrosine phosphorylation of 180-185 kDa proteins, including not only Her2 but also Her3 and Her4 receptors, when they were expressed on the surface of breast cancer cells. These mAbs do not cross-react with Her3 or Her4 as demonstrated by competition study. Receptor phosphorylation was also observed with the cell lines transfected with Her2 or a chimeric receptor consisting of the extracellular domain of Her2 and the transmembrane and cytoplasmic domains of epidermal growth factor receptor. Selected mAbs were tested for their ability to change cell morphology, and one specific mAb, mAb74, induced cell morphology changes and apoptosis.

Animals↗
PubMed1996

Fu-Ling, a Chinese herbal drug, modulates cytokine secretion by human peripheral blood monocytes.

Fu-Ling, the sclederma of Poria cocos (Schw.) Wolf, has long been used as a sedative and diuretic in traditional Chinese herbal medicine. Our study demonstrated that the substances extracted from Fu-Ling by 50% hot ethanol significantly augmented the secretion of interleukins IL-1 beta and IL-6 6 h after in vitro cultivation of human peripheral blood monocytes. The augmented effect was dose dependent. Tumour necrosis factor-alpha (TNF-alpha) secretion was also increased as the cells were treated with 0.4 mg/ml or higher doses of Fu-Ling extract. By contrast, Fu-Ling extract significantly suppressed the secretion of transforming growth factor-beta (TGF-beta) 3 h after the in vitro drug treatment. The suppressive effect was shown at doses as low as 0.2 mg/ml of Fu-Ling extract. Since Fu-Ling extract enhanced the secretion of immune stimulators (IL-1 beta, IL-6 and TNF-alpha) but suppressed the secretion of an immune suppressor (TGF-beta), the substance in 50% hot ethanol extract of Fu-Ling might have potentiated the immune response. Fu-Ling extract was further fractionated by reverse-phase column chromatography and high-performance liquid chromatography (HPLC). The components showing activity in modulating the cytokine secretion were relatively high in hydrophobicity.

Adjuvants, Immunologic↗
PubMed1996

Si-jun-zi-tang regulate granulocyte macrophage colony-stimulating factor secretion by human peripheral blood mononuclear cells.

Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study, human peripheral blood monocytes were treated in vitro with 50% hot ethanol extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu, Gancao and Fuling). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture supernatant at 3 hours and 18 hours were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSF secretion in a dose-dependent manner. Baizhu showed no statistically significant effect on GM-CSF secretion 18 hours after in vitro drug-treatment. Fuling, by contrast, significantly augmented GM-CSF secretion in a dose-dependent manner after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on GM-CSF secretion at 3 hours but significantly augmented GM-CSF secretion when the cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM-CSF secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the suppressive effect of Dangshen and Gancao on GM-CSF secretion.

Dose-Response Relationship, Drug↗
PubMed1995

Humoral immunity to aerosolized staphylococcal enterotoxin B (SEB), a superantigen, in monkeys vaccinated with SEB toxoid-containing microspheres.

Staphylococcal enterotoxin B (SEB) toxoid-containing microspheres were tested for efficacy in rhesus monkeys as a vaccine candidate for respiratory SEB toxicosis and toxic shock. Forty monkeys were randomly separated into 10 groups of four monkeys each: 9 groups were vaccinated with the microspheres via combinations of mucosal and nonmucosal routes, and 1 group served as nonvaccinated controls. Both vaccinated and nonvaccinated monkeys were then challenged with a high lethal dose of SEB aerosol. Monkeys primed with an intramuscular dose of the microspheres followed by an intratracheal booster all survived the SEB challenge. Overall, monkeys with an intratracheal booster generally had the highest antibody levels, which is consistent with their high survival rate and lower rate of illness. Protective immunity was correlated with antibody levels in both the circulation and the respiratory tract. The protection was not due to the depletion or anergy of SEB-reactive T cells, since SEB-induced proliferation in cultures of circulating lymphocytes was not significantly reduced after the microsphere vaccination. It is evident that the nonsurvivors did not die of systemic anaphylaxis or hypersensitivity because the monkeys did not die immediately after SEB challenge and there were no significant differences in histamine levels between the vaccinated and control monkeys before and after SEB challenge. The antibodies seemed to neutralize the SEB that got into the airway and the circulation.

Aerosols↗
PubMed1995

The effect of Evodia rutaecarpa extract on cytokine secretion by human mononuclear cells in vitro.

The effect of Evodia rutaecarpa extract on cytokine secretion by human mononuclear cells in vitro was investigated. Evodia rutaecarpa extract of various concentrations in mononuclear cell culture medium showed biphasic effects on the secretion of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony stimulating factor (GM-CSF) by the mononuclear cells. Generally speaking, a low to medium level of Evodia rutaecarpa extract, in concentrations ranging from 10% to 30%, showed significant stimulating effects on the secretion of IL-1 beta, IL-6, TNF-alpha and GM-CSF. On the other hand, high level of Evodia rutaecarpa extract, with concentration more than 40%, lost its stimulating effects. Moreover, reaction time affected the stimulating effects of Evodia rutaecarpa extract on cytokine secretion by mononuclear cells. Mononuclear cell culture medium containing Evodia rutaecarpa extract that was allowed to react for 18 or 24 hours showed significantly better stimulating effects than that reacted for 1 or 3 hours.

Cells, Cultured↗
PubMed1995

Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds.

Some human chronic dermal wounds treated with recombinant platelet-derived growth factor-BB (rPDGF-BB) show increased healing coupled with fibroblast activation and granulation tissue formation. To determine whether endogenous PDGF is associated with healing and nonhealing dermal ulcer phenotypes, we developed monoclonal antibodies capable of recognizing the three isoforms of PDGF, AA, AB, and BB dimers, and capable of discriminating between two alternatively spliced A chain transcripts. We detected little PDGF isoform expression in normal skin and in nonhealing dermal ulcers. In contrast, in surgically created acute wounds and chronic ulcers treated with rPDGF-BB, markedly upregulated levels of PDGF-AA (long form) were found. In both types of wounds, increased PDGF-AA was detected primarily in capillaries and fibroblasts, although in rPDGF-BB-treated chronic wounds, widespread expression of PDGF-AA was somewhat delayed. With continued treatment, the long form of PDGF-AA, which can preferentially bind extracellular matrix, was expressed only in capillaries, while fibroblasts began synthesizing the short form of PDGF-AA. Within capillaries, all endothelial cells and varying numbers of pericytes and smooth muscle cells contained PDGF-AA. In all wounds, macrophages and keratinocytes were not a major contributor. While PDGF-BB and PDGF-AB were present in a minority of healing wounds, they were usually present at lower levels than PDGF-AA. PDGF-beta receptors, which bind only PDGF-BB and not other isoforms, were found in normal skin and granulation tissue, providing a molecular basis for treating human chronic wounds with exogenous rPDGF-BB.

Adult↗
PubMed1994

Infiltration of CD4+ T cells into cornea during development of Onchocerca volvulus-induced experimental sclerosing keratitis in mice.

Sclerosing keratitis is the major cause of blindness due to onchocerciasis caused by the parasite Onchocerca volvulus. Although the importance of T cells in the pathogenesis of onchocerciasis has been suggested, their precise role in onchocercal sclerosing keratitis has not yet been defined. Using immunohistological techniques and a murine model of onchocercal sclerosing keratitis, we have performed a temporal analysis of the inflammatory T cells infiltrating into the cornea at Days 4, 7, and 21 following intrastromal challenge with soluble O. volvulus antigens into presensitized mice. The maximum number of CD3+ T cells were observed in the corneal stroma at Day 21 when sclerosing keratitis was most severe. The majority (> 85%) of the CD3+ T cells were CD4+ at all time points. A few infiltrating cells bore IL-2 receptors indicating possible activation of a small fraction of the T cells. These results suggest that CD4+ T cells play an important role in onchocercal sclerosing keratitis.

Animals↗
PubMed1994

The B cell antigen receptor complex: mechanisms and implications of tyrosine kinase activation.

The B cell receptor is a multimeric receptor complex whose constituent chains appear to mediate distinct and possibly interrelated functions. In this review we have focused on how one chain, immunoglobulin (Ig)-alpha, may function to activate tyrosine kinases and the consequences of that activation. The cytoplasmic domain of Ig-alpha contains a consensus sequence, the antigen recognition homology 1 (ARH 1) motif, which is found in Ig-beta and other antigen recognition receptor associated chains. We argue that this conserved structure reflects an underlying conserved mechanism of secondary effector activation. Our data also indicates that the specificity of each motif (i.e., the elements which restrict secondary effector binding to particular motifs) is encoded within divergent sequences found in each ARH 1 motif. In the particular case of kinase activation by Ig-alpha, the subsequent phosphorylation of multiple tyrosines on Ig-alpha, Ig-beta, CD19, CD22 and possibly other functionally related chains form recruitment sites for a myriad of secondary signal transducers. In this model, proximal tyrosine kinases and phosphatases do not function so much to mediate the linear transfer of information as to establish and modulate an interrelated network of signal transducers capable of driving complicated cellular responses.

Amino Acid Sequence↗
PubMed1994

Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D.

Mice (BALB/cJ, C3H/HeN, and C3H/HeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C3H/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an important cofactor in intoxication. In a time course study of the illness, prominent pathological changes characterized by blood congestion and thickening of alveolar septa were seen in the lung, while blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen, congestion, inflammation, and lymphoid cell depletion were the major reactions. The pathological features of the mice had many similarities to those of rhesus monkeys intoxicated with intravenous SEB. The actinomycin D-primed C3H/HeJ mice are thus an ideal mouse model for studying SEB toxicosis and toxic shock.

Animals↗
PubMed1994

Localization of binding sites of staphylococcal enterotoxin B (SEB), a superantigen, for HLA-DR by inhibition with synthetic peptides of SEB.

Staphylococcal enterotoxins are major causes of food poisoning and toxic shock syndrome. Their ability to bind to major histocompatibility complex (MHC) class II molecules has been suggested to be the first step in the mechanism whereby they cause illness. By flow cytometric analysis, the sites of interaction of staphylococcal enterotoxin B (SEB) with HLA-DR molecules were probed in the present study by inhibiting the binding of biotinylated SEB to a human T-cell line (HUT-78) with synthetic peptides of SEB. Five peptides of SEB gave significant inhibition of binding: a peptide containing amino acids 9 to 20 [SEB(9-20)], SEB(30-38), SEB(61-70), SEB(90-114), and SEB(169-181). One peptide, SEB(39-51), enhanced binding. Among the inhibitory peptides, SEB(90-114), a peptide spanning the entire disulfide loop, showed the most efficient inhibition of binding. Peptides SEB(9-20) and SEB(39-51) include amino acid residues that have been identified by previous mutation studies (J.W. Kappler, A. Herman, J. Clements, and P. Marrack, J. Exp. Med. 175:387-396, 1992) as being important in binding to MHC class II. Amino acids lining the alpha 5 groove of SEB have also been postulated to be involved in binding to MHC class II molecules. However, only two of the residues that line the alpha 5 groove of SEB, His-12 and Tyr-17, are on peptide SEB(9-20) that inhibits binding. These results confirm previous studies that implicated the amino-terminal portion of the molecule in binding to MHC class II molecules and further indicate an important role for residues in other regions, particularly the disulfide loop.

Amino Acid Sequence↗