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Biomedical subjects

T C Lee

Publications and source records attributed to T C Lee.

At least 19 recordsLinked to original sources
PubMed1995

Sodium arsenite induces chromosome endoreduplication and inhibits protein phosphatase activity in human fibroblasts.

Arsenic, strongly associated with increased risks of human cancers, is a potent clastogen in a variety of mammalian cell systems. The effect of sodium arsenite (a trivalent arsenic compound) on chromatid separation was studied in human skin fibroblasts (HFW). Human fibroblasts were arrested in S phase by the aid of serum starvation and aphidicolin blocking and then these cells were allowed to synchronously progress into G2 phase. Treatment of the G2-enriched HFW cells with sodium arsenite (0-200 microM) resulted in arrest of cells in the G2 phase, interference with mitotic division, inhibition of spindle assembly, and induction of chromosome endoreduplication in their second mitosis. Sodium arsenite treatment also inhibited the activities of serine/threonine protein phosphatases and enhanced phosphorylation levels of a small heat shock protein (HSP27). These results suggest that sodium arsenite may mimic okadaic acid to induce chromosome endoreduplication through its inhibitory effect on protein phosphatase activity.

Arsenites↗
PubMed1995

Differential cytotoxicity of cadmium to rat embryonic fibroblasts and human skin fibroblasts.

In order to identify why cadmium is differentially toxic to humans and rats, we compared cadmium-induced cytotoxic responses in rat embryonic fibroblasts (REF) and human skin fibroblasts (HFW). According to the values of the lethal concentration 50% for cadmium, REF were about 13-fold more sensitive than HFW to cadmium acetate (1.5 vs 25 microM). Furthermore, progression of S phase cells was more severely delayed by cadmium in REF than in HFW. At doses that killed 90% of REF or HFW (5 or 50 microM, respectively), 50% of DNA synthesis was inhibited in REF, whereas DNA synthesis was not apparently inhibited in HFW. The differential sensitivity to cadmium could not be simply due to different basal levels of metallothionein, since the cellular metallothionein content in HFW was only 1.6 times that in REF, and metallothionein was apparently induced by cadmium in both cells with similar synthesis rates. Furthermore, elevation of cellular metallothionein levels by zinc sulfate pretreatment decreased cadmium toxicity in both cell types, but did not alter their relative sensitivity to cadmium. The differential sensitivity was also not due to differences in cadmium accumulation, since HFW accumulated more cadmium than REF after a 24-hr exposure to 1 or 5 microM cadmium acetate. Although most of the cadmium remained in the cytoplasm, the nuclei of REF contained 12-fold more cadmium than nuclei of HFW (1.31 vs 0.11 micrograms Cd/mg nuclear protein). Therefore, our results indicate that a high level of cadmium accumulation in nuclei of REF may be responsible for cell killing through breakdown of nuclear functions.

Animals↗
PubMed1995

Quantitative arteriography of apparently normal coronary segments with nearby or distant disease suggests presence of occult, nonvisualized atherosclerosis.

OBJECTIVES: The aim of this study was to evaluate, using quantitative arteriography, whether the diameter of visually normal coronary segments might be influenced by the relative proximity of visually apparent disease. BACKGROUND: Severity of coronary artery lesions is commonly referenced against a presumed normal nearby coronary segment with the presumption that visually smooth segments are relatively free of atherosclerotic disease. METHODS: Angiograms from 136 male patients with focal coronary disease were examined, and visually normal segments in the proximal portions of the major vessels were identified for measurement of mean segment diameters. Normal segments with immediately adjacent disease were compared with normal segments with distal disease in the same vessel and compared with normal segments in vessels for which the only other visible disease was in distant vessels. Angiograms with entirely normal findings from 26 age-matched men with atypical chest pain were used as controls. Segments were measured after nitroglycerin administration by means of computer-assisted quantitation. RESULTS: Mean diameters of visually normal segments with distant disease were smaller than those of control segments (p < 0.05). Normal left main and proximal left anterior descending coronary artery segments in patients with disease within the same vessel were significantly smaller than normal segments in patients with distant disease (p < 0.05). Normal segments with immediately adjacent disease had smaller mean diameters than normal segments with distal disease in the same vessel (p < 0.05). CONCLUSIONS: Visually normal coronary segments have progressively smaller lumen diameters, depending on the relative proximity of visible disease. Measurement of percent stenosis on the basis of the diameter of apparently normal adjacent reference segments can result in underestimation of coronary lesion severity.

Cardiac Catheterization↗
PubMed1995

Enhanced insulin-like growth factor molecules in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by activated alveolar macrophages (AM), alveolar epithelial cell proliferation and interstitial matrix, and immune complex deposition. Spontaneous release of competence and progression-type growth factors and their associated binding proteins may contribute to the pathologic features of IPF. To study the role of insulin-like growth factor (IGF) molecules in IPF we evaluated spontaneous release of IGF-I and IGFBP-3 in bronchoalveolar lavage cells from control subjects and from patients with IPF. IGF-I levels were similar compared with those in control subjects. In contrast, IGFBP-3 was significantly increased in IPF. In situ hybridization of open lung biopsies showed IGF-I to be abundant in IPF lung tissue in alveolar macrophages, interstitial mesenchymal cells, and epithelial cells. Northern, Western ligand blotting, reverse transcription PCR, and radioimmunoassay suggested that immune complexes stimulate expression of IGFBP-3 in mononuclear phagocytes in a time- and dose-dependent manner bearing strong similarities to stimulation by LPS. These data are compatible with the hypothesis that IGFBP-3 increases the bioactivity of IGF-I derived from a variety of lung tissues contributing to the fibrosis and remodeling seen in IPF.

Adult↗
PubMed1995

The optimal management of hairy cell leukaemia.

Hairy cell leukaemia is an uncommon B cell chronic lymphoproliferative disorder characterised by circulating lymphocytes displaying prominent cytoplasmic projections. Therapy is initiated for severe cytopenias or recurrent infections. Splenectomy, the first standard treatment, is now less commonly used as primary treatment. Interferon-alpha (IFN alpha) induces partial responses in most patients but complete responses in only a few. Adverse effects from IFN alpha are common but not life-threatening. The ability of two newer purine analogues, pentostatin (2'-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine), to induce long-lasting complete remissions in the majority of patients has revolutionised the treatment of this disease. Cladribine is emerging as the treatment of choice because of its favourable toxicity profile, brief duration of treatment, high percentage of unmaintained complete remissions and low incidence of relapse.

Antineoplastic Agents↗
PubMed1995

Light exposure decreases IOP in rabbits during the night.

Elevated IOP observed in rabbits during the dark phase of the circadian cycle decreased rapidly and reversibly when rabbits were exposed to light during the dark phase. The decrease of IOP does not result from decreased aqueous flow and only part of the decrease requires intact ocular sympathetic innervation.

Animals↗
PubMed1994

Tuberous sclerosis associated with neurofibromatosis: report of a case.

Neurofibromatosis and tuberous sclerosis are phakomatous syndrome diseases. They are both inherited as autosomal dominant diseases. Neurofibromatosis type 1 and tuberous sclerosis very seldom occur together. We report a 16-year-old male who had characteristics of these two diseases. This patient had all the criteria for a definitive diagnosis of tuberous sclerosis such as: classical shagreen patches, periungual fibroma, retinal hamartomata, facial angiofibroma, renal angiomyolipomata, and subependymal glial nodules on computed tomography. He also had the three presumptive diagnostic criteria: cardiac rhabdomyoma, seizure history and first degree relatives with tuberous sclerosis. The patient had more than six café-au-lait spots, the greatest diameter of which exceeded 15 mm in diameter. Multiple neurofibromas, one plexiform neurofibroma, axillary freckling and optic gliomas were also found on his body. These criteria are sufficient for a diagnosis of neurofibromatosis type 1 to be made. The skin biopsies were also consistent with the disease. Apart from the patient's mother and younger sister, who had tuberous sclerosis, there was no other person with neurofibromatosis type 1 in his immediate family. We believe that tuberous sclerosis was inherited from his mother and that neurofibromatosis type 1 may have resulted from mutation.

Adolescent↗
PubMed1994

Binding of heparin and compound Y to endothelial cells stimulates the synthesis of an antithrombotic heparan sulfate proteoglycan.

The mechanism by which heparin and antithrombotic agents, including a cyclic octaphenolsulfonic acid (compound Y), stimulate the synthesis of an antithrombotic heparan sulfate by endothelial cells in culture was investigated. Compound Y increases the amount of heparan sulfate from the cell surface and secreted to the medium by endothelial cells by three-fold. Binding experiments have shown saturation of the endothelial cell receptors at a concentration of 0.16 microM for heparin and 2.7 microM for compound Y. The kinetic binding constants (Ks) for compound Y and heparin were 1,333 nM and 42 nM, respectively. It was also shown that both compounds bind to the same receptors. The Scatchard plots indicated that 1,319 nmoles compound Y and 35 nmoles heparin bound per microgram cell protein, indicating that 40-fold more molecules of compound Y bound to the receptors when compared to heparin. No significant internalization of the compounds was observed.

Animals↗
PubMed1993

Normal human mesothelial cells and mesothelioma cell lines express insulin-like growth factor I and associated molecules.

Insulin-like growth factor (IGF) I has important growth regulatory functions in normal growth and development. IGF-I is also a mitogen for a number of cancer cell lines; however, its autocrine effect has not been well established. In this study, the expression of IGF-I, its receptor, and its major serum-binding protein were examined in 5 normal human mesothelial (NHM) cell samples and 11 pleural mesothelioma cell lines. All NHM cells and mesothelioma cell lines expressed IGF-I, IGF-binding protein 3 (IGFBP-3), and IGF-I receptor mRNA by either Northern blot or reverse transcription polymerase chain reaction analysis. IGF-I (0.136 +/- 0.024 ng/ml, mean +/- SEM) and IGFBP-3 (18.5 +/- 3.2 ng/ml) proteins were readily detected in the conditioned medium of mesothelioma cell lines but were not greater than corresponding measurements in that of NHM cells (IGF-I, 0.120 +/- 0.080 ng/ml; IGFBP-3, 15.9 +/- 1.3 ng/ml). Exogenous recombinant IGF-I stimulated cell proliferation of NHM cells, demonstrating the presence of a functional IGF-I receptor. Our results suggest that IGF-I may function as an autocrine growth stimulus in normal proliferating mesothelial cells, which may contribute to their malignant transformation.

Carrier Proteins↗
PubMed1993

Induction of chromatid breaks and tetraploidy in Chinese hamster ovary cells by treatment with sodium arsenite during the G2 phase.

Treatment of Chinese hamster ovary (CHO) cells with sodium arsenite during the G2 phase induced poorly condensed chromosomes and chromatid breaks. The induction of chromatid breaks was confirmed by the appearance of micronucleated cells after arsenite-treated G2 cells were allowed to re-enter interphase. When the duration of the G2 phase was artificially divided into 4 periods, more chromatid breaks were induced by treatment with arsenite during the very early G2 phase (or G2/S boundary). In addition to the induction of chromatid breaks, arsenite treatment also remarkably retarded the re-entry of mitotic cells into interphase. By replating and incubating arsenite-treated G2 cells in drug-free medium, we subsequently observed the appearance of a population of cells whose DNA content was between 4C and 8C, and metaphase cells with near-tetraploid chromosome numbers in the next mitotic division.

Animals↗
PubMed1993

Mechanisms of stimulation of interleukin-1 beta and tumor necrosis factor-alpha by Mycobacterium tuberculosis components.

The granulomatous immune response in tuberculosis is characterized by delayed hypersensitivity and is mediated by various cytokines released by the stimulated mononuclear phagocytes, including tumor necrosis factor-alpha (TNF alpha) and IL-1 beta. We have demonstrated that Mycobacterium tuberculosis cell wall component lipoarabinomannan (LAM), mycobacterial heat shock protein-65 kD, and M. tuberculosis culture filtrate, devoid of LPS as assessed by the Amebocyte Lysate assay, stimulate the production of TNF alpha and IL-1 beta proteins and mRNA from mononuclear phagocytes (THP-1 cells). The effect of LAM on the release of these cytokines was specific, as only LAM stimulation was inhibited by anti-LAM monoclonal antibody. Interestingly, we found that LAM and Gram-negative bacterial cell wall-associated endotoxin LPS may share a similar mechanism in their stimulatory action as demonstrated by inhibition of TNF alpha and IL-1 beta release by monoclonal antibodies to CD14. Anti-CD14 monoclonal antibody MY4 inhibited both TNF alpha and IL-1 beta release with LAM and LPS but no effect was observed with other mycobacterial proteins. An isotype antibody control did not inhibit release of cytokines under the same experimental conditions. M. tuberculosis and its components upregulated IL-1 beta and TNF alpha mRNAs in THP-1 cells. Nuclear run-on assay for IL-1 beta demonstrated that LAM increased the transcription rate. The induction of IL-1 beta was regulated at the transcriptional level, in which these stimuli acted through cis-acting element(s) on the 5' flanking region of the IL-1 beta genomic DNA. M. tuberculosis cell wall component LAM acts similarly to LPS in activating mononuclear phagocyte cytokine TNF alpha and IL-1 beta release through CD14 and synthesis at the transcriptional level; both cytokines are key participants in the host immune response to tuberculosis.

Antibodies, Monoclonal↗
PubMed1993

Pedicle fixation: an adjuvant for the treatment of thoracolumbar metastases.

For a long time, radiotherapy was considered as the best treatment for spinal metastases. However, radiotherapy alone could not resolve the problem of pathological fracture which is an important complication of spinal metastases. In this paper, we introduce pedicle fixation system as an adjuvant to radiotherapy to treat eight patients with thoracolumbar metastases. The result was encouraging that all the patients achieved spinal stabilisation and all but one had immediate postoperative relief of back pain. The operation time was short and none of the patients required a blood transfusion. Tissue diagnosis was possible through this approach.

Adult↗
PubMed1992

Glutathione S-transferase pi in an arsenic-resistant Chinese hamster ovary cell line.

A glutathione S-transferase (GST) was purified from an arsenic-resistant Chinese hamster ovary cell line, SA7. The SA7 GST was shown to catalyse the conjugation of glutathione and ethacrynic acid, a specific substrate for Pi class GST. Its N-terminal amino-acid sequence has 80% identical residues to that of rat GST P and human GST pi. Thus, the GST purified from SA7 cells belongs to the Pi family. Treatment with Cibacron Blue or ethacrynic acid, which are GST inhibitors, significantly decreased the resistance of SA7 cells to sodium arsenite. On the other hand, pretreatment of SA7N cells, a partial revertant of SA7 cells, with sublethal doses of sodium arsenite, cadmium acetate or zinc sulphate resulted in re-elevation of GST activities and the cells regained the arsenic resistance. The regained arsenic resistance was well correlated with the levels of GST pi which were induced dose-dependently by zinc sulphate. Heat-shock treatment (45 degrees C for 10 min) did not increase GST pi expression or arsenic resistance of SA7N cells. The results indicate that GST pi is possibly involved in the mechanism of arsenic detoxification.

Amino Acid Sequence↗
PubMed1992

Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts.

Muscle-restricted transcription of the skeletal alpha-actin gene is controlled in part by a positive regulator, serum response factor (SRF), and a negative regulator, F-ACT1, which bind competitively to the most proximal serum response element (SRE1). We show here that F-ACT1 is identical to a transcription factor recently cloned and described as YY1, NF-E1, delta, or UCRBP. We found that although the DNA-binding activity of SRF accumulates during myogenesis, that of YY1 diminishes simultaneously. Myoblasts rendered incapable of differentiation by BrdUrd treatment exhibited the highest level of YY1 and the lowest level of SRF activities. Transfected SRF could directly transactivate the skeletal alpha-actin promoter by overcoming the inhibitory effect of BrdUrd-induced YY1. The transactivation depends on intact SRE DNA elements and requires the DNA-binding/dimerization domain of SRF as well as its C-terminal half rich in serines and threonines. Since the functions of YY1 and SRF appear to be developmentally regulated, the convergence of their binding sites upon the SRE constitutes an integrated mechanism whereby temporal and spatial muscle gene expression may be accomplished.

Actins↗
PubMed1992

A novel CoA-independent transacetylase produces the ethanolamine plasmalogen and acyl analogs of platelet-activating factor (PAF) with PAF as the acetate donor in HL-60 cells.

In this study, we demonstrate the presence of a unique membrane-associated transacetylase that transfers the acetate group from platelet-activating factor (PAF) to lysoplasmalogen (in the presence of EDTA and sodium acetate) with the formation of 1-alk-1-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine (alk-1-enylacetyl-GPE). The identity of alk-1-enylacetyl-GPE was confirmed by acid hydrolysis, phospholipases A2 or C treatment and derivatization by fluorodinitrobenzene. The transacetylase has no requirement for Ca2+, Mg2+, or CoA and a broad pH optimum (7.0-8.0) with Km values of 12.0 microM for PAF and 106.4 microM for lysoplasmalogens. The enzyme activity from the isolated membrane fraction is not changed when whole cells are supplemented with 20:4, induced to differentiate into granulocytes, or treated with ionophore A23187. Radyllyso-sn-glycero-3-phosphocholine (GPC), radyllyso-GPE, acyllyso-sn-glycero-3-phosphoserine (GPS), acyllyso-sn-glycero-3-phosphoinositol (GPI), alkyllyso-sn-glycero-3-phosphate (GP), acyllyso-GP, or cis-9-octadecen-1-ol can also serve as acetate acceptors, whereas alkylglycerol, acylglycerol, or cholesterol are inactive. Differences in substrate acceptor specificity, sensitivity toward phenylmethylsulfonyl fluoride, and response to temperature suggest that the CoA-independent transacetylase and the CoA-independent transacylase that transfers long-chain acyl moieties are two separate enzymes. With intact differentiated HL-60 cells, [3H]acetate from [3H]PAF can be incorporated into alk-1-enylacetyl-GPE in the presence of ionophore A23187, but not in its absence. Moreover, phospholipase A2 inhibitors (p-bromophenacyl bromide and mepacrine) block the transacetylation process in whole cell system. These results indicate the production of alk-1-enyllyso-GPE is a rate-limiting factor for the subsequent transacetylation step during cell activation. We conclude that the transacetylase may participate in the biosynthesis of ethanolamine plasmalogen and acyl analogs of PAF, in vivo, fine-tuning of PAF biological responses, and cross-talk between de novo and remodeling pathways of PAF biosynthesis.

Acetates↗
PubMed1992

Posttreatment with sodium arsenite alters the mutational spectrum induced by ultraviolet light irradiation in Chinese hamster ovary cells.

Arsenic, a potent carcinogen, fails to induce gene mutations in mammalian cells. However, posttreatment of ultraviolet light (UV) irradiated cells with sodium arsenite synergistically enhances the mutation frequency on the hypoxanthine (guanine) phosphoribosyltransferase locus. To investigate the molecular mechanism of the comutagenic effects of sodium arsenite, we characterized the alterations of nucleotide sequences in 30 UV-induced and 39 sodium arsenite enhanced hprt mutants from Chinese hamster ovary K1 cells by direct sequencing of mRNA-PCR amplified cDNA. The majority of sequence alterations derived from UV irradiation (80%) and from sodium arsenite posttreatment (70%) were single base substitutions. UV irradiation induced all types of base substitutions. Among them, 57% were transversions. The frequency of transversions increased to 70% in sodium arsenite enhanced mutants. While base substitutions observed in UV-induced mutants were evenly distributed along with the whole coding region, exons 3 and 8 were most frequently mutated in sodium arsenite enhanced mutants. Sodium arsenite posttreatment did not alter the strand bias for mutation induction, i.e., 73% and 78%, of the mutations were located on the non-transcribed strand in UV-induced and sodium arsenite enhanced mutants, respectively. In contrast to UV-induced mutations, bases at the 5' position of TT and the 3' position of CT sequences were the most frequent mutation sites observed in sodium arsenite enhanced mutants. We hypothesize that sodium arsenite may interfere with the process of mutation fixation of TT and CT dimers during DNA replication.

Animals↗