Search PubMed⌕ Search

Biomedical subjects

C L Yu

Publications and source records attributed to C L Yu.

158 records · Page 9Linked to original sources
PubMedDate not supplied

The mechanisms of the inhibitory effects of liver extract on lymphocyte proliferation. III. The effects of arginase on DNA polymerase activities.

The incorporation of labeled precursors into DNA, RNA and protein in phytohaemagglutinin (PHA)-prestimulated human lymphocytes was maximally inhibited by liver extract (LEx) or arginase at 24 h. The activities of DNA polymerase alpha, beta and gamma were less inhibitable by these agents than was [3H]thymidine incorporation. The inhibition of DNA, RNA and protein syntheses by either LEx or arginase is probably due to arginine depletion by arginase activity, since their syntheses were similarly inhibited when cultured in an arginine-free medium in the absence of arginase. These results indicate that arginase nonspecifically inhibits the activities of DNA polymerase. The inhibition is probably due to arginine depletion.

Animals↗
PubMedDate not supplied

Tamm-Horsfall glycoprotein (THG) purified from normal human pregnancy urine increases phagocytosis, complement receptor expressions and arachidonic acid metabolism of polymorphonuclear neutrophils.

Tamm-Horsfall glycoprotein (THG) purified from normal human pregnancy urine was found to increase polymorphonuclear neutrophil (PMN) phagocytosis (46.57 +/- 3.54% in the medium versus 75.85 +/- 5.37% in the presence of 25 micrograms/ml THG) after 30 min preincubation. The phagocytosis-enhancing activity of THG was dose-dependent (5-50 micrograms/ml) and was possibly mediated by the increased expressions of complement receptor type 1 (CR1) and type 3 (CR3) on the neutrophils. The release of [3H]arachidonic acid and prostaglandin E2 (PGE2), but not thromboxane B2 (TXB2), from neutrophils were also significantly enhanced by THG. Using 3,3'-dihexyloxacarbocyanine iodide as indicator, THG (25 micrograms/ml) depolarized the membrane potential of PMN after 30 min preincubation. In addition, THG exhibited a specific membranotropic effect with PMN. It is conceivable that THG binds to the cell surface and depolarizes the membrane potential of PMN which subsequently enhances the release of arachidonic acid metabolites and the translocation of the complement receptors to the membrane. These biochemical events lead to the increment of PMN phagocytosis and suggests that THG may play an important role in the defense mechanisms of the urinary tract in that a large amount of THG is usually present.

Arachidonic Acid↗
PubMedDate not supplied

Tamm-Horsfall urinary glycoprotein enhances monokine release and augments lymphocyte proliferation.

Tamm-Horsfall glycoprotein (THG) purified from pregnancy urine was found to stimulate normal human mononuclear cell (MNC) proliferation at a concentration greater than 10 micrograms/ml. This stimulation was non-specific because the percentage of B and T cell subpopulations including CD20, CD3, CD4, CD8 and CD4/CD8 ratio was not changed by THG. THG not only bound to human mononuclear cells but depolarized the membrane potential, increased 22Na+ uptake and enhanced the expression of IL-2R and HLA-class II antigens on these cells. The concentrations of sIL-2R, sCD4 and sCD8 in the THG-stimulated MNC culture supernatants were significantly increased compared with control supernatants. In addition, overnight incubation of THG (5-50 micrograms/ml) with MNC dose-responsively enhanced the syntheses of IL-1 beta, IL-6 and TNF-alpha by monocytes, with a maximal effect at 25 micrograms/ml. This monokine releasing activity of THG could be neutralized by a specific antibody against THG. When monocytes/macrophages were depleted from mononuclear cells by incubating with lysosomotropic methyl ester of L-leucine, THG retained the capability of stimulating lymphocytes proliferation but to a lesser degree. These results suggest that urinary THG activates monocytes to synthesize large amount of monokines through its membrane effect. The released monokines subsequently stimulate lymphocytes expressing IL-2R and HLA-class II antigens and finally lead to cell proliferation.

Antigens, CD↗
PubMedDate not supplied

Interleukin 8 modulates interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha release from normal human mononuclear cells.

Recombinant human interleukin 8 (IL-8) enhanced the release of inflammatory cytokines including interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) from normal human mononuclear cells in a dose-related manner (from 1 ng/ml to 10 ng/ml with a maximal effect at 5 ng/ml) when the cells incubated with IL-8 for 24 h. This cytokine-releasing activity of IL-8 is temperature-dependent and required protein synthesis since low temperature (4 degrees C) and cycloheximide (100 micrograms/ml) minimized the cytokine release from MNC. However, when IL-8 concentration was greater than 20 ng/ml, the cytokine release was suppressed. For further investigating the subcellular mechanism of the adverse effect of high dose IL-8 (20 ng/ml) in cytokine synthesis, human mononuclear cells (1 x 10(6)/ml) were stimulated with PHA (1 microgram/ml) in the presence of 20 ng/ml IL-8 for 3 days. We found not only [3H]thymidine incorporation of MNC was tremendously inhibited but DNA fragmentation appeared. Subsequently, the cell cycle of PHA-stimulated MNC retarded in the phase of G0/G1. These results suggest that in low concentration (5-10 ng/ml) IL-8 not only activated neutrophil phagocytosis but facilitated the release of inflammatory cytokines from mononuclear cells. Higher dose of IL-8 (more than 20 ng/ml) conversely suppressed these cytokine release from damaged cells by its cytotoxic effect. This newly found cytokine-releasing activity of IL-8 may play a role in the modulation of inflammation.

Cell Cycle↗
PubMedDate not supplied

Embryonic apoptosis-inducing proteins exhibited anticancer activity in vitro and in vivo.

A 54 Kd apoptosis-inducing protein with novel amino acid sequence has been purified from the conditioned medium of the embryonic cell line, C3H 10T1/2 cells. An apoptosis-inducing protein identified to be fetal fetuin and a 60 Kd apoptosis-inducing protein have also been found in fetal serum and fresh embryo extract, respectively. Interestingly, a common characteristic of these embryonic apoptosis-inducing proteins is that they selectively induced apoptosis in cancer without affecting normal cells. For example, the 54 Kd protein selectively induced apoptosis in 10 out of 12 cancer cell lines without affecting 12 normal cell lines we tested. Fetal fetuin, on the other hand, selectively induced apoptosis in 5 cancer cell lines without affecting the 3 normal cell lines we tested. In vivo, tumor animal model study showed that fetal fetuin enhanced survival in leukemia-bearing mice and strongly inhibited the formation of prostate cancer in a PC-3 prostate cancer model in mice. A working hypothesis has been proposed to aid in the study of the mechanism by which the embryonic apoptosis-inducing proteins selectively induced apoptosis in cancer without affecting normal cells. This hypothesis states that due to the retro-differentiational characteristic of malignancy, cancer cells may re-express the signal transduction machinery for development-related apoptosis, which is otherwise to be normally expressed by embryonic, but not by adult cells. The embryonic apoptosis-inducing proteins may therefore induced apoptosis in cancer but not in normal cells and may be developed as an anticancer agent. This new concept may constitute a new approach for cancer therapy, which we tentatively designated as "Retro-differentiational Apoptosis Cancer Therapy", (R-ACT).

Animals↗
PubMedDate not supplied

Decreased spontaneous and lipopolysaccharide stimulated production of interleukin 8 by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.

OBJECTIVE: Interleukin 8 (IL-8) acts as a potent chemotactic cytokine and also as an autocrine factor for polymorphonuclear neutrophils (PMN), thus amplifying the acute inflammatory reaction. We undertook to study the IL-8 producing capacity of PMN in patients with systemic lupus erythematosus (SLE). METHODS: PMN from twelve patients with active SLE, from fifteen patients with inactive disease and from sixteen healthy individuals were incubated for 24 hours in medium alone, or in medium with lipopolysaccharide (LPS) or TNF-alpha. The IL-8 concentration in the culture supernatants was measured by an enzyme linked immunosorbent assay. RESULTS: We found that the spontaneous and LPS-stimulated, but not TNF-alpha-stimulated, production of IL-8 by the PMN of active SLE patients were significantly lower than that of healthy individuals. The impaired IL-8 production by SLE-PMN was linked to disease activity but not to the administration of steroid, because incubation of normal PMN or inactive SLE-PMN with prednisolone (1 microgram/ml and 5 micrograms/ml) for 24 hours did not affect IL-8 production. In addition, IL-8 production increased in three active SLE patients after effective treatment with immunosuppressants but not in two cases of ineffective treatment, in the follow-up study. CONCLUSION: These results suggest that decreased IL-8 production is one of the defects of PMN in patients with active SLE, which might predispose SLE patients to infection.

Adolescent↗
PubMedDate not supplied

The reactivity of sera from patients with systemic lupus erythematosus to seven different species of single and double stranded deoxyribonucleic acids.

OBJECTIVE: Anti-DNA antibodies are frequently found in the serum of patients with systemic lupus erythematosus (SLE). To understand whether the avidity of SLE sera to different species of single-stranded (ss) and double-stranded (ds) DNA is different or not, the reactivity of active SLE sera to seven species of DNA from viral, bacterial, piscine, and mammalian sources was compared. METHODS: Nineteen sera from patients with active SLE were studied for their reactivity to different ssDNA and dsDNA from Escherichia coli (EC), Micrococcus lysodeikticus (ML), Clostridium perfringens (CP), calf thymus (CT), salmon testis (ST), human placenta (HP) and lambda phage by ELISA. The dsDNA was purified by treating it with S1 nuclease and proteinase K, followed by Sephacryl S-300 gel filtration. The ssDNA was purified by absorption on a hydroxyapatite column after heat-cleavage of the dsDNA. RESULTS: The reactivity of SLE sera to 7 species of dsDNA was not significantly different and they recognized a more widely shared epitope. In contrast, the reactivity of these sera to 7 species of ssDNA was erratic and the antigens could be grouped into high (CP and HP), medium (EC, ML, CT, and ST) and low (lambda-phage) antigenicities. CONCLUSION: The anti-ssDNA and anti-dsDNA antibodies of SLE patients recognize more widely shared determinants on the DNA of seven different species. Lambda-phage DNA shows the poorest immunogenicity among them.

Adolescent↗