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Biomedical subjects

C L Yu

Publications and source records attributed to C L Yu.

At least 109 records · Page 6Linked to original sources
PubMed1992

Increased spontaneous release of cytidine deaminase by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus.

Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449 +/- 1.358 U/5 x 10(6) PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003 +/- 2.637 U/5 x 10(6) PMN) but not in inactive (5.358 +/- 1.624 U/5 x 10(6) PMN) SLE. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 x 10(-7) M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794 +/- 0.178) compared with normal controls (1.300 +/- 0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients.

Adult↗
PubMed1992

Alterations of mitogenic responses of mononuclear cells by arsenic in arsenical skin cancers.

We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non-arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non-endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 x 10(-7) M) was added to PHA-stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology--arsenic. Arsenic seems to play a role as a co-stimulant of PHA similar to interleukin-1.

Arsenic↗
PubMed1992

Regulation of the junB gene by v-src.

The proteins encoded by cellular and viral src genes are believed to be involved in the transmission of mitogenic signals, the nuclear recipients of which are largely unknown. In this work, we report that four different v-src-transformed cell lines from three different species possess elevated levels of junB transcripts. Transient expression of junB promoter-chloramphenicol acetyltransferase constructs in NIH 3T3 cells was used to demonstrate that the increase in junB transcripts was specifically associated with v-src expression and could not be recapitulated with a c-src, v-H-ras, or v-raf expression vector. Deletion mutants were used to localize the v-src-responsive region in the junB promoter to a 121-nucleotide region encompassing the CCAAT and TATAA elements. This region is distinct from one in the 5' untranslated region of the junB gene which is required to maintain its high-level basal expression. Point mutagenesis of the junB TATAA box completely abolished v-src responsiveness, suggesting that proteins which bind to this element are modified by src transformation. Several v-src and c-src mutants were used to demonstrate that elevated tyrosine kinase activity of src proteins is required for the observed effects on junB expression. Finally, homology between the TATAA box regions of junB and the unrelated but src-responsive gene 9E3/CEF-4 suggests that modulation of gene activity through proteins which bind to this region may be a recurrent, although not exclusive, theme in src transforming action. Our results suggest that src proteins may modulate some nuclear effectors through pathways not involving cellular ras or raf gene products.

3T3 Cells↗
PubMed1992

Effect of antibodies to double stranded DNA, purified from serum samples of patients with active systemic lupus erythematosus, on the glomerular mesangial cells.

Polyclonal antibodies to double stranded DNA (dsDNA) purified from pooled serum samples of patients with systemic lupus erythematosus (SLE) exerted cytotoxic effects on cultured rat mesangial cells. At concentrations from 5 to 150 IU/ml, antibodies to dsDNA inhibited the incorporation of thymidine labelled with 3H into rat mesangial cells in a dose response manner after three days of culture. In contrast, normal human IgG (1 mg/ml), heat aggregated human IgG (1 mg/ml), N-formyl-methionyl-leucyl-phenylalanine (1 x 10(-7) mol/l), tumour necrosis factor alpha (16 U/ml), lipopolysaccharides (1 microgram/ml), 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) (20 ng/ml), interleukin 1 beta (10 U/ml), and 20% v/v phytohaemagglutinin stimulated mononuclear cell supernatant showed no significant effect on these cells. Anticardiolipin antibody, another autoantibody purified from the serum of patients with SLE, also inhibited the proliferation of rat mesangial cells but to a lesser extent. In the presence of antibodies to dsDNA (100 IU/ml), the mesangial cells became spherical and clustered together, which was very different from the original stellate appearance. These autoantibodies also depolarised the membrane potential of mesangial cells. Antibodies to dsDNA decreased the syntheses of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 by mesangial cells. In an in vivo study, the antibodies to dsDNA showed a strong affinity for the glomeruli when intravenously injected into rats. These results suggest that the nephrotropic antibodies to dsDNA can directly damage the glomerular mesangial cells in addition to the formation of immune complexes with DNA which may cause kidney inflammation and tissue destruction.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Increased excretion of soluble interleukin 2 receptors and free light chain immunoglobulins in the urine of patients with active lupus nephritis.

Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine.

Adolescent↗
PubMed1992

Inhibition of astrocyte proliferation and binding to brain tissue of anticardiolipin antibodies purified from lupus serum.

Polyclonal anticardiolipin antibodies purified from pooled serum samples of patients with systemic lupus erythematosus were shown to have inhibitory effects on cultured normal rat brain astrocytes (RBA-1 cells). Anticardiolipin antibodies at concentrations from 50 to 200 micrograms/ml inhibited the [3H]thymidine incorporation of RBA-1 cells in a dose dependent manner after three days of culture. A kinetic study showed that anticardiolipin antibodies (100 micrograms/ml) maximally inhibit the proliferation of RBA-1 cells (20.6 (5.1)% of the control value) after incubation for one day. In contrast, human gamma globulin (100 micrograms/ml) had no effect on these cells. In the presence of anticardiolipin antibodies (100 micrograms/ml), the RBA-1 cells attached to the bottom of wells became spherical and the expression of glial fibrillary acidic protein in the cytoplasm was slightly reduced. Using 3,3'-dihexyloxacarbocyanine iodide as an indicator, anticardiolipin antibodies depolarised the membrane potential of RBA-1 cells after one day of culture. In addition, the percentage binding of RBA-1 cells with anticardiolipin antibodies was greater than with gamma globulin as determined by flow cytometric analysis. Immunofluorescence staining of brain tissue from BALB/c mice with anticardiolipin antibodies was noted in the corpus callosum, the cellular zone near the corpus callosum, and cells scattered in brain tissue. These results suggest that anticardiolipin antibodies have an inhibitory effect on brain cells and elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus.

Animals↗
PubMed1992

Alteration of intracellular DNA and RNA patterns by liver arginase studied with flow cytometry.

Previous study of lymphocyte proliferation in the presence of liver arginase has indicated that arginine-depletion in the culture medium plays an important role in inhibiting cell proliferation. The inhibitory effect of both liver arginase and arginine-free condition on DNA, RNA and protein syntheses in PHA-stimulated lymphocytes were studied in cultures by measuring the incorporation of labeled precursors. Simultaneously, their influence on DNA and RNA contents in cells stained by acridine orange was investigated by automated flow cytometry. With 3 micrograms/ml arginase, the syntheses of DNA, RNA and protein were markedly inhibited after 72 h of culture. The degrees of inhibition were close to that induced in an arginine-free condition. The DNA and RNA contents of the individual cell, either cultured with 3 micrograms/ml arginase or in arginine-free medium, were arrested in G0/G1 phase. The results of cell arrest in G0/G1 phase were similar whether the cells were cultured for 24, 48 or 72 h.

Animals↗
PubMed1992

The simultaneous use of electrocochleogram, brainstem auditory evoked potential and facial muscle EMG in cerebellopontine angle tumor removal.

In six cases of acoustic neurilemmoma, electrocochleogram (ECOchG), brainstem auditory evoked potentials (BAEP) and facial muscle electromyograms (EMG) were recorded to monitor facial nerve and brainstem function. Under isoflurane and nitrous oxide anesthesia, we recorded ECOchG from the tympanic membrane, BAEP from the scalp needle, and facial muscle EMG from the mentalis muscle. During surgery, the body temperature was kept above 36.5 degrees C, and PaCO2 above 30 mmHg. In all cases, the peak N1 of ECOchG and wave I of BAEP had identical latencies throughout the monitoring period. The response was faster and the amplitude was higher in the ECOchG recordings. For calculation of the I-III or I-V interpeak latency of BAEP, the wave I of BAEP could be confirmed more quickly and precisely by the peak N1 of ECOchG. During tumor removal, the embedded facial nerve pathway in the tumor was identified by electric stimulation of the intracranial facial nerve, followed by evoked facial muscle EMG. Facial nerve function was confirmed by nerve traction or direct electric stimulation after total removal of the tumor. No facial palsy or other neurologic sequelae was found after the operations.

Adult↗
PubMed1992

Down-regulation of ras and myc expression associated with mdr-1 overexpression in adriamycin-resistant tumor cells.

The murine melanoma tumor cells, B16-BL6, are a recognized model for experimental and spontaneous metastasis. B16-BL6 cells express a lower metastatic phenotype upon acquisition of resistance to adriamycin. Using this novel system, the role of ras, c-myc, and multidrug-resistant gene (mdr1) expression in the metastatic and drug-resistant phenotype was examined. The metastatic cells expressed a high level of c-Ki-ras and c-myc, whereas down-regulation of both proto-oncogenes was observed in the adriamycin-resistant cells. The mdr1 gene, which encodes P-glycoprotein of the drug-resistant superfamily gene, was overexpressed in drug-resistant melanoma cells. These results suggest that altered expression of genes that regulate cellular proliferation and growth may be a determinant of metastasis and drug sensitivity of tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Alterations of skin-associated lymphoid tissue in the carcinogenesis of arsenical skin cancer.

We investigated the skin-associated lymphoid tissue in arsenical skin cancers, including 14 Bowen's disease, 6 basal cell carcinoma and 6 squamous cell carcinoma patients from an endemic area by immunohistochemical and morphometric methods. There was a progressive decrease of Langerhans cells in the order of normal skin, normal appearing edge and arsenical cancers. A disruption of the uniform Langerhans cell dendrites was also noticed. The Langerhans cell density in arsenical tumors did not correlate with the peritumoral infiltrates. The prominent infiltrated cells in the peritumoral area had T cell markers. The number of peritumoral T lymphocytes in squamous cell carcinoma was significantly less than that of Bowen's disease and basal cell carcinoma. Peritumoral mononuclear infiltrates in Bowen's disease and squamous cell carcinoma showed a higher helper/suppressor T cell ratio than that in basal cell carcinoma. This may be accounted for by a selective increased recruitment of helper T cells to the tumor infiltrates in Bowen's disease and squamous cell carcinoma.

Arsenic Poisoning↗
PubMed1991

Ras GTPase-activating protein physically associates with mitogenically active phospholipids.

The physical interaction between GTPase-activating protein (GAP) and lipids has been characterized by two separate analyses. First, bacterially synthesized GAP molecules were found to associate with detergent-mixed micelles containing arachidonic but not with those containing arachidic acid. This association was detected by a faster elution time during molecular exclusion chromatography. Second, GAP molecules within a crude cellular lysate were specifically retained by a column on which certain lipids had been immobilized. The lipids able to retain GAP on such columns were identical to those which were shown previously to be most active in blocking GAP activity. The association between lipids and GAP was dependent upon magnesium ions. Lipids unable to inhibit GAP activity were also unable to physically associate with GAP. The tight association of GAP with these lipids was predicted by and helps to rationalize their ability to inhibit GAP activity.

Animals↗
PubMed1991

Inhibitory effects of anticardiolipin antibodies on lymphocyte proliferation and neutrophil phagocytosis.

Anticardiolipin antibodies purified from serum from patients with systemic lupus erythematosus (SLE) by cardiolipin micelles were studied for their effects on lymphocytes and neutrophils. At a concentration of 160 micrograms/ml they markedly suppressed the [3H]thymidine incorporation of mononuclear cells stimulated by phytohaemagglutinin (4.9 (SEM 1.9%) of the control) and pokeweed mitogen (26.7 (10.5%) of the control). In addition, anticardiolipin antibodies changed the cell cycle of phytohaemagglutinin stimulated lymphocytes such that the S and G2+M phases were significantly diminished (G0/G1 = 64.62%, S = 20.59%, G2+M = 14.78% in the presence of normal human IgG v G0/G1 = 86.07%, S = 10.32%, G2+M = 3.59% in the presence of anticardiolipin antibodies). The suppression of lymphocyte proliferation by anticardiolipin antibodies was shown not to be caused by an alteration of T cell subpopulations. However, the interleukin 2 receptors on the cell surface and the soluble interleukin 2 receptors in the supernatant of phytohaemagglutinin stimulated mononuclear cells were decreased in the presence of anticardiolipin antibodies. On the other hand, the phagocytic activity of neutrophils was 40% inhibited at a higher concentration of anticardiolipin antibodies (300 micrograms/ml) through suppression of C3b/C4b and Fc receptors on polymorphonuclear leucocytes. These results suggest that anticardiolipin antibodies exert inhibitory effects on both lymphocytes and phagocytes in addition to the coagulation cascade. These newly found activities of anticardiolipin antibodies were mediated by the non-specific membranotropic property of the antibodies.

Autoantibodies↗
PubMed1991

Immunoregulatory effects of phospholipase A2 (PLA2) on the proliferation of human lymphocytes.

Extracellular phospholipase A2 (PLA2) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA2 exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA2 enhanced the proliferation of PHA MNC (maximal increase was 37.0 +/- 5.67%). Conversely, at concentrations over 10 U/ml, PLA2 markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 +/- 2.89%). PLA2 was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA2 at a low concentration. In addition, PLA2 displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA2, was parallel to the change of percentage of helper T cells. Furthermore--a CD4-rich population was proved more susceptible to PLA2 effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA2, abrogated the biphasic effect of PLA2 on PHA MNC proliferation. These results suggest that PLA2 plays a regulatory role on immune reactions by modulating the percentage of helper T cells.

Deoxyribonucleases↗
PubMed1991

Defective expression of neutrophil C3b receptors and impaired lymphocyte Na(+)-K(+)-ATPase activity in patients with systemic lupus erythematosus.

In our previous report, we demonstrated that the functions of phagocytes and lymphocytes were defective in patients with systemic lupus erythematosus (SLE). In an attempt to further clarify the defective mechanisms of these cells, 25 active SLE, 10 bronchial asthma patients (BA) on corticosteroids and 25 age and sex-matched normal individuals were investigated for the expression of membraneous C3b receptors, ionophore-induced 45Ca(2+)-uptake, mitochondrial potentials and phagocytic activity of neutrophils. We found decreased expression of C3b receptors on SLE PMN in both resting (37.2 +/- 3.7% of the normal controls) and FMLP-stimulated (68.3 +/- 7.1% of the normal controls) conditions, whereas the C3b receptor expression on BA-PMN receiving long-term steroid treatment was not different from normal controls. This suggests that the defective phagocytosis of SLE PMN is in the recognition, but not in the ingestion phase because of the normal function of Ca(2+)-influx and mitochondrial activity in SLE PMN. On the other hand, hyporesponsiveness to PHA stimulation (stimulation index: 127.4 +/- 46.3 in SLE vs. 311.2 +/- 30.4 in normals, p = 0.0077) was a distinct cell-mediated immune abnormality in our SLE patients. We measured the membrane potential of individual cells using 3,3'-dihexyloxacarbocyanin and found hyperpolarization in resting SLE lymphocytes. However, the membrane polarization of SLE lymphocytes became lower than that of normal cells after PHA stimulation for 3 days. A similar tendency was also found in Na(+)-K(+)-dependent ATPase activity in SLE lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Simple bone cysts. The effects of methylprednisolone on synovial cells in culture.

Ten years ago, a protocol using Depo-Medrol injections was developed for the treatment of unicameral bone cysts. This concept, designed by tumor surgeons and based on theory, has been cautiously approached. However, reproducible results have gradually increased clinical acceptance. Understanding the healing process has been restricted because of the lack of an experimental model. In an attempt to elucidate this mechanism of healing, a cell culture model was used to investigate the effects of methylprednisolone on synovial cells. Initially, three doses of the drug were tested and maximal changes were noted with the concentration of 40 mg/ml. Changes were then quantified by morphology, DNA assay, cell protein analysis, and electron microscopy. Results suggest that methylprednisolone may have a direct effect on the cellular component of unicameral bone cysts.

Bone Cysts↗
PubMed1990

A cytoplasmic protein inhibits the GTPase activity of H-Ras in a phospholipid-dependent manner.

A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.

Animals↗
PubMed1990

Modulation of human lymphocyte proliferation by amino acids.

The amino acids required for phytohaemagglutinin (PHA) induced lymphocyte proliferation were determined by the 3H-thymidine incorporation in amino acid-deficient media. Results indicate that the PHA-stimulated lymphocytes require alanine and serine in addition to 13 other amino acids present in Eagle's minimal essential medium (arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and valine). The omission of any one of the 13 amino acids would stop almost completely the proliferation of PHA-stimulated lymphocytes. The omission of serine from RPMI 1640 medium caused a mean reduction of 64% of cell proliferation, while the addition of alanine to PRMI 1640 culture medium caused a mean increment of 52%. The lymphocyte proliferation appears to be modulated by amino acids in the culture medium, and for optimal growth of lymphocytes, all these 15 amino acids are essential.

Amino Acids↗