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T C Lee

Publications and source records attributed to T C Lee.

At least 109 records · Page 6Linked to original sources
PubMed1998

Successful removal of a hemangioblastoma from the medulla oblongata: case report.

Hemangioblastomas are histologically benign tumors that occur exclusively within the neuraxis, most commonly in the posterior fossa. They are typically cystic tumors located in the cerebellum. Excision of the vascular mural nodules leads to cure. Brain stem lesions are rarely reported. Surgical extirpation of a solid brain stem hemangioblastoma is relatively risky and requires precise microsurgical techniques. We present a woman with a hemangioblastoma embedded in the medulla oblongata. This 33-year-old woman presented with occipital headaches and sensory ataxia. Complete and detailed preoperative imaging studies were followed by successful microsurgical excision of the lesion. The patient recovered completely within 2 weeks after the operation except for mild paresthesia of the legs. Preoperative magnetic resonance imaging and cerebral angiography provided important information regarding the nature, location, and blood supply of this lesion, which facilitated its total removal. The importance of intraoperative identification and control of the feeding artery of the tumor is emphasized.

Adult↗
PubMed1997

Myc represses transcription of the growth arrest gene gas1.

Cell proliferation is regulated by the induction of growth promoting genes and the suppression of growth inhibitory genes. Malignant growth can result from the altered balance of expression of these genes in favor of cell proliferation. Induction of the transcription factor, c-Myc, promotes cell proliferation and transformation by activating growth promoting genes, including the ODC and cdc25A genes. We show that c-Myc transcriptionally represses the expression of a growth arrest gene, gas1. A conserved Myc structure, Myc box 2, is required for repression of gas1, and for Myc induction of proliferation and transformation, but not for activation of ODC. Activation of a Myc-estrogen receptor fusion protein by 4-hydroxytamoxifen was sufficient to repress gas1 gene transcription. These findings suggest that transcriptional repression of growth arrest genes, including gas1, is one step in promotion of cell growth by Myc.

3T3 Cells↗
PubMed1997

Sodium arsenite disturbs mitosis and induces chromosome loss in human fibroblasts.

Arsenite, a unique human carcinogen, induces many types of cytogenetic alterations, such as sister chromatid exchanges, chromosome aberrations, and endoreduplication in a variety of in vivo and in vitro systems. Cytogenetic alterations are frequently associated with cancer development. The purpose of this study was to explore how arsenite induces cytogenetic alterations in human skin fibroblasts (HFW). The present results show that treatment of G2-enriched HFW cells with 5 microM arsenite results in significant delay of cell cycle progression, accumulation of mitotic cells, and prolongation of mitosis. Arsenite-induced G2 and mitotic delay are accompanied by accumulation of cyclin B1 and hyperphosphorylation of cdc2 and Mos proteins. In addition to mitotic delay and prolongation, arsenite treatment also induced out-of-phase centromere separation and alterations of chromosome segregation, such as the appearance of c-metaphase, ball-metaphase, and lagged chromosomes. Unlike spindle poisons, arsenite at the dose range used did not inhibit the spindle fiber formation but conceivably deranges the spindle apparatus. By analyzing the karyotype of established subclones surviving arsenite injury, 18% (8 of 44) showed one chromosome loss, whereas all 26 subclones derived from the untreated cultures were diploid. Furthermore, most arsenite-treated clones manifest prolonged life span (86 +/- 18 population doublings) as compared to those derived from the untreated cultures (44 +/- 11 population doublings). Unfortunately, none became immortal. Collectively, treatment of the G2-enriched HFW cells with arsenite can disturb the mitotic events and subsequently induce chromosome loss.

Arsenites↗
PubMed1997

Intron/exon structure confirms that mouse Zfy1 and Zfy2 are members of the ZFY gene family.

Zfy1 and Zfy2 are homologous zinc finger genes on the mouse Y Chromosome. To ask whether these genes are properly classified as members of the ZFY family, we have characterized and compared their genomic organization to that of mouse Zfx, human ZFX, and human ZFY. We show that Zfy1 has 11 exons distributed across at least 56 kb, and Zfy2 has a minimum of 9 exons distributed across at least 52 kb. The Zfy2 locus contains regions similar in size and sequence to all 11 exons of Zfy1, plus an additional 5' UTR exon. All splice sites conform to the GT-AG rule. There are two instances of additional AG dinucleotides immediately 5' of 3' splice sites. Zfy1 and Zfy2 are homologous to other ZFY family members within the coding region, but the untranslated regions show no sequence similarity. Within the coding region, there is conservation of exon length and splice sites, with each splice preceding the second nucleotide of a codon. We conclude that Zfy1 and Zfy2 are indeed members of the ZFY family, which has evolved from a single common ancestral gene.

Animals↗
PubMed1997

Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1.

Muscle-restricted transcription of sarcomeric actin genes is negatively controlled by the zinc finger protein YY1, which is down-regulated at the protein level during myogenic differentiation. To identify cellular proteins that might mediate the function/stability of YY1 in muscle cells, we screened an adult human muscle cDNA library using the yeast two-hybrid cloning system. We report the isolation and characterization of a novel protein termed YAF2 (YY1- associated factor 2) that interacts with YY1. The YAF2 cDNA encodes a 180 amino acid basic protein (pI 10.5) containing a single N-terminal C2-X10-C2 zinc finger. Lysine clusters are present that may function as a nuclear localization signal. Domain mapping analysis shows that the first and second zinc fingers of YY1 are targeted for YAF2 protein interaction. In contrast to the down-regulation of YY1, YAF2 message levels increase during in vitro differentiation of both rat skeletal and cardiac muscle cells. YAF2 appears to have a promyogenic regulatory role, since overexpression of YAF2 in C2 myoblasts stimulates myogenic promoter activity normally restricted by YY1. Co-transfection of YY1 reverses the stimulatory effect of YAF2. YAF2 also greatly potentiates proteolytic cleavage of YY1 by the calcium- activated protease m-calpain. The isolation of YAF2 may help in understanding the mechanisms through which inhibitors of myogenic transcription may be antagonized or eliminated by proteolysis during muscle development.

Actins↗
PubMed1997

Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model.

Asbestosis is characterized by increased collagen deposition along the walls of terminal respiratory bronchioles that extends into the alveolar ducts and septae. Alveolar macrophages are activated and release growth factors that stimulate mesenchymal cell proliferation and enhanced formation of extracellular matrix. Both insulin-like growth factor-I (IGF-I), and transforming growth factor beta (TGF-beta) regulate cellular growth and promote matrix accumulation and are hypothesized to play important roles in asbestosis. We performed immunohistochemistry using polyclonal antibodies to specific synthetic peptides of the three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) and to IGF-I on lungs of sheep treated intratracheally with chrysotile asbestos. All three TGF-beta isoforms were found in bronchial and bronchiolar epithelium, macrophages, and bronchial and vascular smooth muscle in control lungs. The distribution of TGF-beta was increased in these lung constituents as fibrotic lesions developed. Fibrotic lesions additionally demonstrated intense immunostaining of all three TGF-beta isoforms that localized to the extracellular matrix zones with little staining of interstitial cells. In the control sheep lungs, IGF-I staining was detected in bronchial and bronchiolar epithelium, bronchial glands, bronchial and vascular smooth muscle, endothelium, and macrophages. IGF-I immunostaining was detected in macrophages in peribronchial fibrosis and in fibroblasts along the periphery of and within lesions, but not in the extracellular matrix. Metaplastic proliferating epithelium and macrophages were strongly immunoreactive for IGF-I in advanced lesions. Our data demonstrate different immunostaining patterns for IGF-I and TGF-beta in asbestosis, with IGF-I in the cellular periphery and TGF-beta in the extracellular matrix consistent with a complementary role in stimulating interstitial fibroblast proliferation and new collagen deposition in areas of active fibrosis.

Animals↗
PubMed1997

Ex vivo adenoviral-mediated gene transfer to lung isografts during cold preservation.

BACKGROUND: Although whole-organ gene transfer has been reported in heart and liver transplant models, it has not been well characterized in lung grafts. The aim of this study was to determine the feasibility of ex vivo gene transfer to rat lung isografts during cold preservation using an adenoviral vector. METHODS: F344 rats, divided into four groups, underwent orthotopic left lung transplantation. In group I, lung grafts were flushed with adenovirus carrying the beta-galactosidase gene. After storage at 10 degrees C, grafts were implanted in recipient animals. Group II underwent the same procedure but graft storage was at 4 degrees C. Groups III (10 degrees C) and IV (4 degrees C) served as controls. On postoperative day 5, recipients were sacrificed, and native and transplanted lungs were examined. RESULTS: In group I, all animals showed successful, albeit patchy, gene expression. This occurred in 2 of 4 animals in group II, the other 2 showing no expression. Transduced cells were consistent morphologically with endothelial cells and pneumocytes. A minimal mononuclear inflammatory infiltrate was present. Control groups showed no transduction. CONCLUSIONS: It is feasible to perform ex vivo adenoviral-mediated gene transfer to rat lung isografts during cold preservation.

Adenoviridae↗
PubMed1997

Disgust and disgust sensitivity in blood-injection-injury and spider phobia.

Blood-injection-injury (BII) phobics and spider phobics show markedly different cognitive, psychophysiological, and motoric reactions to activating stimuli. These observations have led theorists to question whether the emotion of fear mediates both phobias. The present study examined the role of disgust and disgust sensitivity in these subtypes of specific phobia. BII phobics, spider phobics, and nonphobics completed questionnaires and rated pictures of specific objects on fear and disgust scales. Questionnaire data indicated that phobic participants were higher than nonphobics on fear, and also on disgust sensitivity. The reaction of BII phobics to pictures of medical stimuli was one of disgust, rather than fear. The reaction of spider phobics to pictures of spiders was a combination of fear and disgust, though fear appeared to predominate. Results are discussed in view of current theories of emotional factors in specific phobia.

Adolescent↗
PubMed1997

Population pharmacokinetics of intravenous caffeine in neonates with apnea of prematurity.

OBJECTIVE: The study the population pharmacokinetics of caffeine after intravenous administration to premature infants with apnea. METHODS: A prospective, blinded parallel study in which daily caffeine citrate doses of 30, 15, and 3 mg/kg were administered over 7 days by intermittent intravenous infusion. Arterial blood samples (three to six per patient) were assayed for caffeine content by means of HPLC. Population pharmacokinetic modeling was performed with NONMEM. RESULTS: Clearance (L/hr) = (0.00000399 . current weight [grams]) + (0.000128 . postnatal age [days]). For gestational age > 28 weeks, volume of distribution (L) = (0.000764 . weight [grams] + (0.0468 . postnatal age [days]); for gestational age < or = 28 weeks, volume of distribution (L) = (0.000755 . weight [grams]) + (0.0224. postnatal age [days]). Interpatient variability (coefficient of variation, in percent) was approximately 25% for clearance and approximately 11% for volume of distribution. Intrapatient error (standard deviation) was 3.9 mg/L. There was insignificant bias between observed and model-predicated serum caffeine concentrations in a separate group of 30 infants. CONCLUSIONS: Caffeine was well tolerated at all doses. Clearance was markedly lower and volume of distribution was higher than the values reported previously for term infants and adults. Both parameters were significantly influenced by postnatal age and current body weight, whereas volume of distribution in infants > 28 weeks' gestational age was higher than that in more premature babies. The predictive performance and the clinical application of the derived population models was satisfactorily shown.

Apnea↗
PubMed1997

Liposome-mediated gene transfer to lung isografts.

OBJECTIVES: Our objective were to determine the feasibility, efficacy, and safety of in vivo and ex vivo liposome-mediated gene transfer to lung isografts. METHODS: Fischer rats were divided into three main groups: (1) Nontransplant setting: Liposome-chloramphenicol acetyl transferase cDNA was intravenously injected, and lungs were harvested at different time points: 2, 6, 12, and 24 hours; 2, 5, 8, and 21 days (n = 3). Chloramphenicol acetyl transferase activity was determined in lungs, hearts, livers, and kidneys. The distribution and type of transfected cells were evaluated by in situ hybridization. Lung toxicity was assessed by arterial oxygen tension, histology, and tumor necrosis factor-alpha levels. (2) In vivo graft transfection: Left lungs were transplanted 6 hours, 4 hours, and 15 minutes after intravenous injection and were assessed for chloramphenicol acetyl transferase activity and arterial oxygen tension on postoperative day 2. (3) Ex vivo graft transfection: Grafts were infused ex vivo with either 660 micrograms (n = 3) or 330 micrograms (n = 3) of DNA complexed to liposomes and stored at 10 degrees C for 4 hours. Chloramphenicol acetyl transferase activity was assessed 44 hours after transplantation. RESULTS: Transgene expression was detected in endothelial cells, macrophages, and interstitial cells. Chloramphenicol acetyl transferase activity was present as early as 2 hours, increased significantly between 6 hours and 8 days, and then decreased to minimal levels by 21 days. Chloramphenicol acetyl transferase activity was greatest in donor lungs and hearts and minimal in livers and kidneys. Arterial oxygen tension was normal in treated animals. Inflammation was minimal, and tumor necrosis factor-alpha levels increased only sevenfold in treated animals. CONCLUSION: In vivo and ex vivo liposome-mediated gene transfer to lung isografts allows significant transgene expression with minimal effects on graft function.

Animals↗
PubMed1997

Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants.

The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.

Amoxicillin↗
PubMed1997

Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates.

OBJECTIVE: To evaluate the effects of intravenous midazolam on haemodynamic variables and cerebral blood flow velocity (CBFV) and to determine the pharmacokinetics using a population approach in very low birthweight (VLBW) ventilated infants. METHODOLOGY: Physiological variables were measured at predetermined times in 10 infants with birthweight < or = 1500 g following a bolus dose of intravenous midazolam (0.1 mg/kg). Heart rate, mean arterial blood pressure (MAP) and transcutaneous CO2 (TcPCO2) were recorded and CBFV was assessed by Doppler ultrasound. Midazolam concentrations were also measured and pharmacokinetic parameters determined using a population modelling package. RESULTS: No change in heart rate occurred during the study period, while the MAP decreased by 3 mmHg 5 min after midazolam administration compared to baseline values. A non-significant fall in TcPCO2 was seen at 20 min. Mean CBFV decreased from the baseline by 12% at 5 min, then returning to predose values. Midazolam concentrations were in the range shown to be effective in sedation of paediatric intensive care infants with the elimination being delayed in comparison to older children. CONCLUSIONS: As only minor cerebral and haemodynamic effects were found with the use of midazolam in stable ventilated preterm infants, it appears to be a safe, short-term sedative agent.

Analysis of Variance↗
PubMed1997

Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases.

Transforming growth factor beta (TGF-beta), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-beta isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-beta isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-beta isoforms in malignant mesothelioma, with TGF-beta 1 in the stroma but TGF-beta 2 in the tumor cells. These data are consistent with an important role for TGF-beta in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases.

Administration, Inhalation↗
PubMed1996

Analysis of events associated with serum deprivation-induced apoptosis in C3H/Sol8 muscle satellite cells.

Satellite cells are the source of new muscle fibers in postnatal skeletal muscle growth and regeneration. Regulation of satellite cell survival is of fundamental importance in maintaining normal muscle function. Here we describe and characterize a tissue culture model of satellite cell apoptosis. Kinetic studies indicate that serum deprivation triggers a set of sequential events: early cell death, transient cell cycle traverse, and delayed cell death. The satellite cell death occurs by apoptosis based on the internucleosomal DNA laddering, in situ DNA end-labeling, and the requirements for de novo protein synthesis and extracellular calcium influx. The transient period of cell cycle progression (7-11 h after serum withdrawal) is accompanied by temporal induction of members of the immediate early gene family, such as c-myc, c-fos, and SRF, and appears to precede the delayed phase of cell death. Satellite cell apoptosis can be suppressed by several growth factors and by blocking the activity of calpain, a calcium-regulated protease. The late phase of apoptosis is marked by selective activation of ubiquitin-mediated protein conjugation and degradation. This study defines several control points where satellite cell apoptosis may be genetically or pharmacologically intervened.

Animals↗
PubMed1996

Squalene inhibits sodium arsenite-induced sister chromatid exchanges and micronuclei in Chinese hamster ovary-K1 cells.

Arsenic, widely distributed throughout our environment, is a well-established human carcinogen. We report here that squalene, a natural fish oil, is a potential agent in the reduction of sodium arsenite-induced sister chromatid exchange (SCE) and micronuclei in Chinese hamster ovary (CHO-K1) cells. Squalene dose-dependently inhibited sodium arsenite-induced SCE. At the highest concentration (160 microM), squalene reduced the SCE frequency from 8.85 to 6.47 SCEs per cell which is very close to the background level (5.82 SCEs per cell). Sodium arsenite dose-dependently induces micronuclei in CHO-K1 cells, and squalene at 80 microM significantly inhibits arsenite-induced micronuclei. However, squalene did not eliminate the killing effects of arsenite on the cells and only slightly decreased intracellular accumulation of arsenic.

Animals↗
PubMed1996

Isolation and characterization of the recA gene of Xanthomonas campestris pv. campestris.

A 1.8-kb NsiI-StuI fragment containing the recA gene of Xanthomonas campestris pv. campestris was cloned by a PCR-based approach and complementation of Escherichia coli HB 101. Sequence analysis of this fragment revealed an ORF (orf343) of 1,032 bp able to encode a protein of 343 amino acids with a calculated MW of 37,021 Da, a size similar to the values detected by in vitro system and Western blotting. It showed 69.6% identity to the E. coli RecA in amino acid sequence. Amino acid residues of the E coli RecA associated with functional activities are conserved in this Xc17 RecA. The recA mutant, L1, constructed by gene replacement, was sensitive to ultraviolet irradiation and methyl methanesulfonate, and deficient in homologous recombination.

Amino Acid Sequence↗