Biomedical subjects

T C Lee

Publications and source records attributed to T C Lee.

At least 145 records · Page 8Linked to original sources

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↗

PubMed1995

Complications of transpedicular reduction and stabilization of the thoracolumbar spine.

Between July 1990 and January 1994, 160 patients underwent transpedicular reduction and stabilization using an AO internal fixator. In this series, most of the patients (101 cases) had degenerative spondylolisthesis. The follow-up period ranged from 12 to 36 months. One hundred and thirty one patients (82%) had a good or excellent postoperative outcome. Sixteen (10%) had fair outcomes and 13 (8%) had poor outcomes. There were 26 complications (16%) secondary to this treatment. Improper screw placement was found in five patients, wound infection in four patients and dural tear with cerebrospinal fluid leakage in two patients. Two patients were suspected of having an iatrogenic root injury during the insertion of the pedicle screws. One patient with advanced spondylosis developed a postoperative neurologic deficit (foot drop). In the follow-up period, there was loss of correction of the alignment in five patients, screw breakages in three patients, screw pull-out in two patients and loosening of the clamps in another two patients. As most of the complications were preventable or treatable, pedicle fixation system is still highly recommended for the treatment of spondylolisthesis or spinal instability.

Female↗

PubMed1995

[Brain abscess as a complication of ear malignancy: a case report].

Ear infection is the most common cause of brain abscess. A suppurative process in the ear has access to the central nervous system by direct extension or through preformed pathways, either developmental, traumatic or pathologic, or by retrograde spread along the thromobophlebitic vein. Squamous cell carcinoma of middle ear or mastoid cavity is a rare disease and often associated with chronic otitis or chronic draining ear. Ear malignancy easily produces the destruction of temporal bone which may serve as a route for coexistent infection spreading into the brain. This paper reports a case of brain abscess occurring in a patient with temporal bone cancer. To the best of our knowledge, no more than three similar cases have been reported in the literature. The authors suggest that if an otogenic brain abscess is concomitant with infection and granulomatous mass in the ear, biopsy should be performed to rule out malignancy.

Brain Abscess↗

PubMed1994

A proteolytic activity enhanced by arsenite in Chinese hamster ovary cells: possible involvement in arsenite-induced cell killing.

Treatment of Chinese hamster ovary (CHO-K1) cells with 10 microM sodium arsenite for 24 h resulted in enhancement of a proteolytic activity toward the chromogenic substrate CBZ-Phe-Arg-AMC. Presence of dithiothreitol and a pH between 4 and 6 were required for displaying its full hydrolytic activity. According to its substrate- and inhibitor-specificity, this arsenite-induced proteolytic activity was very similar to lysosomal cathepsin B. Arsenite cytotoxicity was further shown to be partially prevented by inhibitors that inhibited the arsenite-induced protease, such as antipain and chymostatin, but not by protease inhibitors without inhibitory effects on the arsenite-induced protease. Our present results suggest that the arsenite-induced protease activity may be involved in arsenite's killing effects.

Animals↗

PubMed1994

Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer-binding protein, TEF-1.

Skeletal alpha-actin (SkA) is representative of the cardiac genes that are expressed at high levels in embryonic myocardium, down-regulated after birth, and reactivated by trophic signals including type beta-transforming growth factors (TGF beta). To investigate the molecular basis for cardiac-restricted and TGF beta-induced SkA transcription, we have undertaken a mutational analysis of the SkA promoter in ventricular myocytes, with emphasis on the role of three nominal serum response elements. Serum response factor (SRF) and the bifunctional factor YY1 are the predominant cardiac proteins contacting the proximal SRE (SRE1). Mutations of SRE1 that prevent recognition by SRF and YY1, or SRF alone, virtually abolish SkA transcription in both TGF beta- and vehicle-treated cells; mutation of distal SREs was ineffective. A mutation which selectively abrogates YY1 binding increases both basal and TGF beta-dependent expression, substantiating the predicted role of YY1 as an inhibitor of SRF effects. However, efficient SkA transcription requires combinatorial action of SRE1 with consensus sites for Sp1 and the SV40 enhancer-binding protein, TEF-1. As isolated motifs, either SRE1- or TEF-1-binding sites function as TGF beta response elements. Induction of the SkA promoter by TGF beta required SRF and TEF-1 in concert, unlike other pathways for TGF beta-dependent gene expression.

Actins↗

PubMed1994

Expression of heme oxygenase in arsenic-resistant human lung adenocarcinoma cells.

We have established arsenic-resistant cells (CL3R) and their subclones from a human lung adenocarcinoma cell line (CL3). CL3R cells and their subclones were maintained in the presence of 4 microM sodium arsenite. They were 6-fold more resistant than CL3 cells to arsenite. Heme oxygenase was expressed in CL3R cells and their subclones, as demonstrated by electrophoretic analysis, Northern blotting, and enzyme activity assay. When CL3R15 cells were grown in arsenite-free medium, their arsenite resistance declined in parallel with their decreasing heme oxygenase activity. Tin-protoporphyrin, a heme oxygenase inhibitor, was found to increase the toxicity of arsenic to CL3R cells. Expression of heme oxygenase might therefore be involved in the mechanism of arsenic resistance. CL3R cells were also shown to be cross-resistant to oxygen-radical generating agents, such as menadione and Adriamycin. Furthermore, sodium arsenite treatment dose-dependently increased the dichlorofluorescein fluorescence in CL3 cells but not in CL3R15 cells. These results suggest that heme oxygenase plays an important role in reducing cellular oxidants that are enhanced by sodium arsenite treatment.

Adenocarcinoma↗

PubMed1994

Severe exfoliative dermatitis associated with hand ischemia during cisplatin therapy.

BACKGROUND: Platinum is one of the most widely used agents in clinical oncology today. Serious toxic effects are well recognized. FINDINGS: To our knowledge, the current report describes the first case of severe allergic exfoliative dermatitis associated with ischemia and necrosis of the hands in a patient who had received multiple doses of this agent. We postulate that the tissue damage was caused by vasospasm of small vessels from the initial injury triggered by platinum or its associated immune complexes. CONCLUSION: Platinum has become an integral part of combination chemotherapy for various solid tumors. Clinicians must recognize its toxic side effects and control them within tolerable limits.

Cisplatin↗

PubMed1994

Reduction and stabilization without laminectomy for unstable degenerative spondylolisthesis: a preliminary report.

Fifty-two patients with unstable degenerative spondylolisthesis treated with the "AO internal fixator" and posterolateral fusion were reviewed. The major purpose of this study is to observe whether this pedicle fixation system could adequately decompress the nervous system tissue by the restoration of the spinal canal and, hence, replace the conventional decompressive laminectomy for the treatment of this disease entity. The results were satisfactory, showing that 92% of the patients with radicular pain, 89% of the patients with low back pain, and 86% of the patients with intermittent claudication improved postoperatively. Observing the results, only two groups of patients with unstable degenerative spondylolisthesis are not suitable for this treatment modality. The first group consists of those patients who have a spondylolisthesis with borderline instability. The second group consists of those patients who have a positive Lasèque's sign.

Adult↗

PubMed1994

Differential cytotoxic effects of arsenic on human and animal cells.

Human fibroblasts (HFW) were 10-fold more susceptible than Chinese hamster ovary (CHO-K1) cells to sodium arsenite. Comparison of cellular antioxidant enzyme activities showed that CHO-K1 cells contained 3- and 8-fold more glutathione-peroxidase and catalase activities, respectively, than HFW cells. Since vitamin E, methylamine, and benzyl alcohol could prevent, in part, the arsenite-induced killing of HFW cells, we suggest that arsenite can induce oxidative damage in HFW cells. We have also established arsenic-resistant cells, SA7 and CL3R, from CHO cells and from a human lung adenocarcinoma cell line (CL3), respectively. The arsenic resistance of SA7 cells was attributed mainly to elevation of glutathione S-transferase pi levels, and that of CL3R cells was possibly due to an increase in heme oxygenase activity. Since induction of heme oxygenase is a general response to oxidative stress, we suspect that the differential toxicity of arsenic to human and animal cells could be due to arsenic's more efficient induction of oxidative damage in human cells.

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↗

PubMed1994

Differentiation induced increase of platelet-activating factor acetylhydrolase in HL-60 cells.

Platelet-activating factor (PAF) acetylhydrolase catalyzes the conversion of PAF to lyso-PAF and acetate. In this study we show that induced cellular differentiation of HL-60 cells grown in chemically defined media by dimethylsulfoxide (DMSO) to granulocytic cells increases the acetylhydrolase activity with a concomitant increased secretion of the enzyme into the media. This increase in acetylhydrolase activity is blocked by the presence of actinomycin D (1 microM) or cycloheximide (1-2 microM) in the culture media. Acetylhydrolase is located both in the cytosolic and particulate fractions; the relative distribution of acetylhydrolase activity in the particulate fraction and cytosol increases and decreases respectively, as the differentiation progresses. The addition of an intracellular protein transport inhibitor, monensin, causes further accumulation of acetylhydrolase activity in the particulate fraction and a decrease in the media, with no effect on the acetylhydrolase activity in the cytosol. Acetylhydrolase in differentiated HL-60 cells acquires properties similar to those of the plasma acetylhydrolase in that it becomes less sensitive to 5,5'-dithiobis-2-nitrobenzoic acid and p-bromophenacylbromide inhibition than the acetylhydrolase in undifferentiated cells. The acetylhydrolase secreted into the media by the differentiated cells was almost totally insensitive to these inhibitors, whereas the acetylhydrolase from the particulate fraction gave an intermediate response; the cytosolic acetylhydrolase was sensitive to both inhibitors. However, the acetylhydrolase secreted by differentiated HL-60 cells has a different electrophoretic mobility, temperature sensitivity, and association with lipoproteins when compared to that of human plasma acetylhydrolase. Collectively, these results indicate cellular differentiation induces intracellular acetylhydrolase activity through a mechanism involving both transcriptional and translational events. Furthermore, the acetylhydrolase synthesized during the DMSO-induced differentiation of HL-60 cells is then secreted into the media via the intracellular membrane transport system for proteins. Based on results obtained with HL-60 cells as a cell model, it is likely that more than one isoform of acetylhydrolase exists in the extracellular milieu.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1994

Bifunctional transcriptional properties of YY1 in regulating muscle actin and c-myc gene expression during myogenesis.

Oncogene expression is generally incompatible with terminal cell differentiation as in myogenesis. We present evidence that this incompatibility can be caused in part by the dual activity of a Kruppel-related zinc finger, YY1 (formerly F-ACT1), in differentially regulating oncogene and muscle-specific gene expression. The c-myc and skeletal alpha-actin gene promoters contain YY1 binding sites thought to act either as positive or negative cis-acting elements. Through manipulating the intracellular level of YY1 by treating primary myoblasts with bromodeoxyuridine (BrdU), which inhibited myogenesis and increased the YY1 protein content, or by transfecting YY1 cDNA expression vector, we show that it can simultaneously inhibit and activate expression of the skeletal alpha-actin and c-myc genes, respectively. The transrepression activity of YY1 solely depends on its C-terminal zinc finger region (amino acids 297-407) while its transactivation function requires an additional N-terminal domain (amino acids 1-90) normally masked in the full-length protein. We propose that the high level of YY1 in proliferating myoblasts might serve to maintain c-myc expression and suppress muscle actin expression, which can then be gradually reversed by downregulating YY1 activity toward myogenesis.

Actins↗

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

Glutathione S-transferase pi facilitates the excretion of arsenic from arsenic-resistant Chinese hamster ovary cells.

We have previously demonstrated that glutathione S-transferase pi (GST pi) is overexpressed in SA7 cells, an arsenic resistant cell line derived from Chinese hamster ovary (CHO) cells. Our present results show that SA7 cells accumulate less arsenic than parental CHO cells and partially revertant SA7N cells. The lower levels of arsenic accumulation in SA7 cells resulted from their faster excretion rates. However, the excretion of arsenic from SA7 cells was significantly inhibited by the GST inhibitors ethacrynic acid and Cibacron blue. Furthermore, when GST pi levels in SA7N cells were re-elevated by zinc sulfate pretreatment, arsenic accumulation decreased and arsenic excretion increased to levels similar to those in SA7 cells. These results suggest that GST pi can facilitate the excretion of arsenic. Such facilitation by GST pi is unlikely to be associated with multi-drug resistant P-glycoprotein, since no overexpression of P-glycoprotein was detected in SA7N and SA7 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1993

Enhanced IL-1 beta and tumor necrosis factor-alpha release and messenger RNA expression in macrophages from idiopathic pulmonary fibrosis or after asbestos exposure.

Idiopathic pulmonary fibrosis (IPF) and asbestosis are fibrotic interstitial lung diseases characterized by alveolar wall fibrosis with accumulation of extracellular matrix, interstitial remodeling, and increased numbers of activated alveolar macrophages. Animal models and in vitro studies have shown that macrophage cytokines, namely IL-1 beta and TNF-alpha, play significant roles in the development of fibrosis. We found significant increases for TNF-alpha release in both diseases (p < 0.01) and a significant increase for IL-1 beta release in asbestosis compared to normal controls (p < 0.01). Also, the mRNA expression of these cytokines was increased in alveolar macrophages from patients with IPF or asbestosis compared with normals. The level of TNF-alpha release in macrophage supernatants correlated with the number of neutrophils per milliliter bronchoalveolar lavage fluid returned. Chrysotile, crocidolite, amosite asbestos, and silica stimulated IL-1 beta and TNF-alpha release and up-regulated their respective mRNA in macrophages or monocytes. To evaluate the role of IL-1 beta and TNF-alpha in the accumulation of extracellular matrix, we studied collagen types I and III and fibronectin gene expression in human diploid lung fibroblasts after short term (2 h) serum-free exposure to recombinant cytokines. Both cytokines up-regulated these genes 1.5- to 3.6-fold. These cytokines have the potential to influence the remodeling and fibrosis observed in the lower respiratory tract in IPF and asbestosis.

Adult↗