Biomedical subjects

Y C Lee

Publications and source records attributed to Y C Lee.

At least 145 records · Page 8Linked to original sources

PubMed2000

Management of malignant pleural mesothelioma: a critical review.

Malignant mesothelioma remains a uniformly fatal disease and best supportive care continues to be the standard treatment. Neither chemotherapy nor surgery has been shown to prolong survival. Radiotherapy is not curative but is useful for prophylaxis against needle-track metastases and for symptom palliation. Combinations of therapies have been tried but most studies were uncontrolled and selection bias makes the results impossible to interpret. The combination of extrapleural pneumonectomy, chemotherapy, and radiotherapy attracted much interest, but the subsequent results were disappointing in a highly selected group of patients. Randomized controlled trials are desperately needed to provide definitive information on experimental treatments. It is also important to develop better measures of disease response and to assess quality of life issues in clinical trials. If patients are to receive therapies other than palliation, they should only do so in the setting of randomized controlled trials under approved protocols.

Brachytherapy↗

PubMed2000

In vivo requirement of activator-specific binding targets of mediator.

There has been no unequivocal demonstration that the activator binding targets identified in vitro play a key role in transcriptional activation in vivo. To examine whether activator-Mediator interactions are required for gene transcription under physiological conditions, we performed functional analyses with Mediator components that interact specifically with natural yeast activators. Different activators interact with Mediator via distinct binding targets. Deletion of a distinct activator binding region of Mediator completely compromised gene activation in vivo by some, but not all, transcriptional activators. These demonstrate that the activator-specific targets in Mediator are essential for transcriptional activation in living cells, but their requirement was affected by the nature of the activator-DNA interaction and the existence of a postrecruitment activation process.

Binding Sites↗

PubMed2000

Transforming growth factor beta(2) (TGF beta(2)) produces effective pleurodesis in sheep with no systemic complications.

BACKGROUND: We have recently shown that transforming growth factor (TGF)beta(2) induces effective pleurodesis in rabbits. However, rabbits have a thin pleura while humans have a thick visceral pleura. The effect of intrapleural administration of TGF beta(2) in animals with a thick pleura and its associated systemic effects have not been investigated. This study was undertaken (1) to develop a new animal model for the study of pleurodesis using sheep which have a thick pleura resembling that of humans; (2) to study the efficacy of TGF beta(2) as a pleurodesis agent in the sheep model; and (3) to assess whether histological changes occur in extrapulmonary organs after intrapleural administration of TGF beta(2). METHODS: Twelve sheep were divided into four groups and were given a single intrapleural injection of TGF beta(2) in a concentration of 1.0 microg/kg, 0.5 microg/kg, 0.25 microg/kg or 0.125 microg/kg to the right pleural cavity via a chest tube. The left pleural cavity served as the control. Any pleural fluid that accumulated after the intrapleural TGF beta(2) injection was collected and analysed. The degree of pleurodesis was graded from 1 (no adhesions) to 8 (complete symphysis >50% of chest wall) at day 14 when the sheep were killed. Biopsy specimens were taken from the lungs and extrapulmonary organs. RESULTS: All sheep that received > or = 0.25 microg/kg TGF beta(2) developed excellent pleurodesis (score = 8) while those that received 0.125 microg/kg had a median score of 6. The pleurodesis score did not exceed 2 in the control (left) side of any sheep. Sheep receiving > or = 0.50 microg/kg TGF beta(2) developed large exudative pleural effusions while those receiving a lower dose did not. The production of effusions neither hindered nor was necessary for inducing pleurodesis. There were no significant fibrotic changes in any of the extrapulmonary organs. CONCLUSION: Intrapleural injection of 0.25-1.0 microg/kg TGF beta(2) produces excellent pleurodesis in a new sheep model with no evidence of extrapulmonary fibrosis.

Animals↗

PubMed2000

A single intrapleural injection of transforming growth factor-beta(2) produces an excellent pleurodesis in rabbits.

The purpose of the present study was to determine whether the intrapleural injection of transforming growth factor beta(2) (TGF-beta(2)) would produce a pleurodesis in rabbits. Single intrapleural injections of TGF-beta(2) at doses of 5.00 microg (n = 12), 1.67 microg (n = 10), 0.50 microg (n = 10), or 0.167 microg (n = 4), or of the parenteral buffer alone (n = 5) were given in a volume of 2 ml to New Zealand white rabbits. Chest tubes were left in place for at least 72 h. Pleural fluid was aspirated at 24-h intervals and was measured and subjected to chemical analysis. The animals were killed 14 d after the injection. The intrapleural injection of TGF-beta(2) resulted in a dose-dependent pleurodesis (on a scale of 0 to 4, where 0 = no pleurodesis and 4 = complete pleurodesis) with mean scores of 3.6, 2.6, 1.5, 0.7, and 0.3 for the groups that received 5.0, 1.67, 0.50, and 0.167 microg of TGF-beta(2) and buffer alone, respectively. Intrapleural injection of the larger doses of TGF-beta(2) resulted in the formation of a large amount of pleural fluid. The fluid had a significantly lower white blood cell (WBC) count and lactate dehydrogenase (LDH) level than did the fluid that results from the intrapleural injection of 10 mg/kg doxycycline or 400 mg/kg talc slurry. On the basis of this study we conclude that a single intrapleural injection of TGF-beta(2) induces pleurodesis in a dose-dependent manner. A dose of 5.0 microg produced satisfactory pleurodesis in almost all of the rabbits so treated. Larger doses of TGF-beta(2) induced larger pleural effusions with relatively low pleural fluid WBC counts and LDH levels. The ability of TGF-beta to produce a pleurodesis in patients with recurrent pleural effusions or pneumothorax should be investigated. A single intrapleural injection of TGF-beta(2) may produce a pleurodesis both safely and painlessly.

Animals↗

PubMed2000

Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2.

ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappaB (NFkappaB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFkappaB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFkappaB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFkappaB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

3T3 Cells↗

PubMed2000

Vascular endothelial growth factor level correlates with transforming growth factor-beta isoform levels in pleural effusions.

BACKGROUND: Recent studies have demonstrated high levels of vascular endothelial growth factor (VEGF) in exudative pleural effusions and a possible etiologic role. The factors regulating VEGF accumulation in the pleural space are unknown. Transforming growth factor (TGF)-beta is a potent stimulator of VEGF expression in vitro. We hypothesized that TGF-beta induces VEGF production in pleural tissues, and, hence, the pleural fluid VEGF levels should correlate with the levels of TGF-beta in pleural fluid of different etiologies. METHODS: Seventy pleural fluid samples were analyzed. These included 20 malignant, 13 post-coronary artery bypass grafting (CABG), 8 parapneumonic, 11 miscellaneous exudative, and 18 congestive heart failure (CHF) pleural effusions. RESULTS: Pleural fluid VEGF levels showed good correlation with those of TGF-beta(1) (r = 0.58; p < 0. 0001), TGF-beta(2) (r = 0.43; p < 0.001), and lactate dehydrogenase (r = 0.65; p < 0.001). The levels of TGF-beta(1) and TGF-beta(2) also were correlated (r = 0.60; p < 0.0001). The median levels of TGF-beta(1) (2,480 pg/mL) and TGF-beta(2) (266 pg/mL) in the CHF group were significantly lower than those in the malignant (TGF-beta(1), 4,902 pg/mL; TGF-beta(2), 428 pg/mL), post-CABG (TGF-beta(1), 5,456 pg/mL; TGF-beta(2), 377 pg/mL), parapneumonic (TGF-beta(1), 5,024 pg/mL; TGF-beta(2), 464 pg/mL), and miscellaneous exudate groups (TGF-beta(1), 7,690 pg/mL; TGF-beta(2), 369 pg/mL). There was no significant difference in TGF-beta(1) and TGF-beta(2) levels among the four exudate groups. CONCLUSIONS: VEGF levels in pleural effusions are significantly correlated with the levels of TGF-beta(1) and beta(2) isoforms. VEGF, TGF-beta(1), and TGF-beta(2) levels were all higher in exudative effusions than in effusions secondary to CHF.

Endothelial Growth Factors↗

PubMed2000

Clinicopathologic characteristics of early gastric cancer in Korea.

Gastric cancer is the most common cause of cancer related death in Korea. Early gastric cancer (EGC), confined to mucosa or submucosa, regardless of lymph node metastasis, is known to have a favorable prognosis. From 1976 to 1995, four thousand nine hundred and twenty eight gastric cancer patients underwent operation at the Severance Hospital, Yonsei University, College of Medicine, Seoul, Korea. Of these, 1,117 patients (22.6%) were diagnosed as EGC and underwent curative operation. Clinicopathologic characteristics were reviewed and survival data was analyzed. The proportion of EGC has increased during the last two decades, from 14.9% during 1976-1985 to 25.8% for 1986-1995. EGC has a wide age distribution range from the thirties to the sixties, with highest incidence in the sixties. The male to female ratio is 1.8:1, without any significant change in last two decades. Most lesions are located in the lower third of stomach (52.3%), and the lesser curvature (52.2%) was the most frequent site in the transverse axis. Macroscopically, the depressed type was the most common (66.1%) followed by the elevated, flat and mixed types, in that order. Tumor confined to the mucosa layer was seen in 52.5%, and lymph node involvement in 11.7%. The depth of tumor invasion correlated with tumor size and regional lymph node involvement. On histopathologic examination, signet ring cell type accounted for 29.6% of all EGCs. Overall 5-year survival rate was 92.7% and the presence of lymph node metastasis significantly affected survival (84.6% versus 96.2%) (p<0.05). In conclusion, the proportion of EGC, in terms of the gastric cancers operated upon, has been increasing in Korea over the last two decades. The introduction of active diagnostic approaches and diagnostic modalities could improve early diagnosis and the cure rate of gastric cancer in Korea.

Adult↗

PubMed2000

Follicular dendritic cell sarcoma presenting as a submucosal tumor of the stomach.

Follicular dendritic cell (FDC) sarcomas, especially those of extranodal origin, are extremely rare, and this entity could easily be missed without a high index of suspicion. We report a case of FDC sarcoma presenting as a submucosal tumor of the stomach in a 45-year-old man. The mass was a spindle and epithelioid mesenchymal tumor with many individually scattered and perivascular aggregates of lymphocytes. Immunohistochemical and ultrastructural studies confirmed the diagnosis. Although more than 50 cases of this tumor have been documented in the English literature, to our knowledge the presentation of FDC sarcoma as a submucosal tumor of the stomach has never been recorded. This case highlights the occurrence of FDC sarcoma as a submucosal tumor of the gastrointestinal tract. We believe that FDC sarcoma should be included in the differential diagnosis of spindle or epithelioid cell tumors of the gastrointestinal hollow viscus to prevent this still under-recognized tumor from being overlooked.

Dendritic Cells, Follicular↗

PubMed2000

The prevalence and pattern of contact lens use in a Singapore community.

PURPOSE: We conducted a cross-sectional survey to determine the prevalence, socio-demographic patterns, and characteristics of contact lens use in an electoral community in Singapore. METHODS: One thousand eight hundred fifteen persons aged between 12-55 years from 768 households were surveyed using a standardized pre-tested questionnaire. RESULTS: The percentage of contact lens wearers in the survey populations was 9.0%. Forty-two percent of surveyed individuals were myopes, 21.8% of whom wore contact lenses. Contact lens wearers tended to be young Chinese females with higher level education and incomes. Most wore monthly disposable or daily wear soft contact lenses. Convenience and cosmesis were the main reasons cited for contact lens wear. Optometrists, who prescribed the bulk of contact lenses, were also the most influential in determining consumers' choice of lenses. CONCLUSION: Information gathered in this population-based survey may be used to facilitate national eye-care planning and provide a baseline for comparison with rates of lens wear found in other countries and in future surveys.

Adolescent↗

PubMed2000

Postoperative seizure outcome after corpus callosotomy in reflex epilepsy.

Flickering light and color patterns, reading, language, movement, decision making, eating, tapping and touching, hot water immersion and auditory stimulation can induce seizures in some epileptic patients. These are known as the "reflex epilepsies". The mechanism of reflex epilepsy is not clear. Recently, we performed anterior two-thirds corpus callosotomies in two reflex epilepsy patients (ages 12 and 14 years), with follow-up for more than three years. Patient 1 had Lennox-Gastaut syndrome with auditory-induced generalized atonic or tonic seizures (startle epilepsy), which decreased by 60% after callosotomy. Patient 2 had Lennox-Gastaut syndrome with somatosensory-induced generalized tonic seizures (tap epilepsy). He was seizure-free for one year immediately after callosotomy, but his seizures recurred with the same degree and frequency as before surgery. The nonsignificant postoperative seizure outcome suggests that the corpus callosum only plays a partial role in seizure generation. Our report also discusses the possible mechanisms of generation of reflex seizures.

Adolescent↗

PubMed2000

Postcallosotomy seizure outcome in hemiconvulsion-hemiatrophy-epilepsy syndrome.

Recently, three patients with hemiconvulsion-hemiplegia-epilepsy syndrome who underwent callosotomy were monitored for more than four years. All patients had atrophy of the right brain hemisphere with left hemiparesis and seizures. Two cases were probably the result of traumatic intracranial hemorrhage and one was due to an unknown cause. Wada tests were done in cases 1 and 2, which showed spared motor function of the atrophic hemisphere, supporting the choice of callosotomy instead of hemispherectomy. Patient 1 had atypical absence seizures and asymmetric generalized tonic seizures before surgery, the latter of which decreased by about 60% after callosotomy. Patient 2 had simple partial seizures of the motor type and complex partial seizures, the latter of which were also induced by touch (somatosensory-induced reflex epilepsy). This patient's complex partial seizures disappeared completely, but the simple partial seizures remained unchanged. Patient 3 had generalized tonic seizures, simple partial seizures of the sensory type and complex partial seizures. After surgery, the frequency of the generalized tonic seizures decreased more than 90%. The simple partial seizures of the sensory type remained unchanged. There were two new types of seizures after surgery, simple partial seizures of the motor type and brief generalized myoclonic jerks. All patients had significant reductions in numbers of seizures of more than 50%.

Adolescent↗

PubMed2000

Effect of combined therapy of oral anti-tubercular agents on theophylline pharmacokinetics.

To evaluate the effects of combined therapy of anti-tubercular agents with theophylline during treatment of concurrent pulmonary tuberculosis and chronic obstructive pulmonary disease or asthma, the clearance and half life of theophylline was estimated in a control group not treated with anti-tubercular agents, a group treated with isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA), and a group treated with INH, RMP and EMB. Clearances of theophylline in the treated groups were significantly lower than in the control group, and the half-life of theophylline was longer than in the control. These results suggest that patients administered combinations of anti-tubercular agents with theophylline require lower doses of theophylline.

Antitubercular Agents↗

PubMed2000

Marfanoid habitus, dysmorphic features, and web neck.

Bilateral pneumothoraces and aortic dilatation developed in a 25-year-old white man with marfanoid habitus, dysmorphic features, web neck, and intellectual impairment. He had physical features suggestive of Shprintzen-Goldberg syndrome. We review the common characteristics of Marfan and Shprintzen-Goldberg syndromes and compare them with our case. Physicians should beware of potential cardiovascular abnormalities in patients with marfanoid habitus and dysmorphic features.

Abnormalities, Multiple↗

PubMed1999

A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo.

Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. We isolated a nuclear factor (designated ASC-2) with such properties by using the ligand-binding domain of retinoid X receptor as a bait in a yeast two-hybrid screening. ASC-2 also interacted with other nuclear receptors, including retinoic acid receptor, thyroid hormone receptor, estrogen receptor alpha, and glucocorticoid receptor, basal factors TFIIA and TBP, and transcription integrators CBP/p300 and SRC-1. In transient cotransfections, ASC-2, either alone or in conjunction with CBP/p300 and SRC-1, stimulated ligand-dependent transactivation by wild type nuclear receptors but not mutant receptors lacking the AF2 domain. Consistent with an idea that ASC-2 is essential for the nuclear receptor function in vivo, microinjection of anti-ASC-2 antibody abrogated the ligand-dependent transactivation of retinoic acid receptor, and this repression was fully relieved by coinjection of ASC-2-expression vector. Surprisingly, ASC-2 was identical to a gene previously identified during a search for genes amplified and overexpressed in breast and other human cancers. From these results, we concluded that ASC-2 is a bona fide transcription coactivator molecule of nuclear receptors, and its altered expression may contribute to the development of cancers.

Amino Acid Sequence↗

PubMed1999

Structural basis for recognition of phosphorylated high mannose oligosaccharides by the cation-dependent mannose 6-phosphate receptor.

Mannose 6-phosphate receptors (MPRs) play an important role in the targeting of newly synthesized soluble acid hydrolases to the lysosome in higher eukaryotic cells. These acid hydrolases carry mannose 6-phosphate recognition markers on their N-linked oligosaccharides that are recognized by two distinct MPRs: the cation-dependent mannose 6-phosphate receptor and the insulin-like growth factor II/cation-independent mannose 6-phosphate receptor. Although much has been learned about the MPRs, it is unclear how these receptors interact with the highly diverse population of lysosomal enzymes. It is known that the terminal mannose 6-phosphate is essential for receptor binding. However, the results from several studies using synthetic oligosaccharides indicate that the binding site encompasses at least two sugars of the oligosaccharide. We now report the structure of the soluble extracytoplasmic domain of a glycosylation-deficient form of the bovine cation-dependent mannose 6-phosphate receptor complexed to pentamannosyl phosphate. This construct consists of the amino-terminal 154 amino acids (excluding the signal sequence) with glutamine substituted for asparagine at positions 31, 57, 68, and 87. The binding site of the receptor encompasses the phosphate group plus three of the five mannose rings of pentamannosyl phosphate. Receptor specificity for mannose arises from protein contacts with the 2-hydroxyl on the terminal mannose ring adjacent to the phosphate group. Glycosidic linkage preference originates from the minimization of unfavorable interactions between the ligand and receptor.

Animals↗

PubMed1999

Bcl3, an IkappaB protein, stimulates activating protein-1 transactivation and cellular proliferation.

Bcl3, an IkappaB protein, was originally isolated as a putative proto-oncogene in a subset of B cell chronic lymphocytic leukemias. Bcl3 was subsequently shown to associate tightly with and transactivate the NFkappaB p50 or p52 homodimer. Herein, we show that Bcl3 stimulates the activating protein-1 (AP-1) transactivation, either alone or in conjunction with transcription integrators steroid receptor coactivator-1 and CREB-binding protein/p300. The C-terminal 158 residues of Bcl3 exhibited an autonomous transactivation function and interacted with specific subregions of the AP-1 components c-Jun and c-Fos, CREB-binding protein/p300, and steroid receptor coactivator-1, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. In addition, anti-HA antibody co-precipitated c-Jun from HeLa cells co-expressing c-Jun and HA-tagged Bcl3, consistent with the idea that Bcl3 directly associates with AP-1 in vivo. Furthermore, microinjection of Bcl3 expression vector into Rat-1 fibroblast cells significantly enhanced DNA synthesis and expression of c-jun, one of the cellular target genes of AP-1. These results suggest that Bcl3 may directly participate in the tumorigenesis processes as a novel transcription coactivator of the mitogenic transcription factor AP-1 in vivo.

Animals↗

PubMed1999

Developmental expression of proprotein convertase 1/3 in the rat.

We have isolated a clone that has 3' end sequence identity with prohormone convertase 1/3 (PC1/3) from a rat islet cDNA library. Northern blot analysis and immunocytochemical studies have confirmed its presence in the endocrine pancreas. Analysis of poly A mRNA from various adult tissues demonstrated that it was relatively abundant in whole brain, lung and spleen, but not detectable in kidney, testis and heart. Using probes consisting of either the coding region or the 3' end sequences, the mRNA transcripts identified were 5.0, 3.0 and 8.5 kb. The 8.5 kb transcript detected has not been described previously. RT-PCR of RNA isolated from rat embryonic tissues using a primer set corresponding to the 3' end of the PC1/3 sequence showed a steady increase of expression in fetal pancreas and intestine during the course of development. In contrast, comparatively high and constant levels of PC1/3 expression were detected in fetal lung, whereas low and constant expression was detected in fetal liver. Double immuno-staining showed that PC1/3 was co-localised with insulin throughout development, and at mid-gestation, PC1/3 immunoreactivity could also be detected within glucagon-producing cells in the developing pancreas. Thus, we have identified a novel PC1/3 mRNA transcript in the rat by using sequence-specific probes and have demonstrated that the developmental expression of prohormone convertase PC1/3 is confined primarily to pancreas and intestine, suggesting that it may play a possible role in regulating growth and differentiation of these tissues.

Animals↗

PubMed1999

Effect of formulation on the systemic absorption of insulin from enhancer-free ocular devices.

Several Gelfoam (absorbable gelatin sponge, USP) based surfactant free devices containing either sodium or zinc insulin were prepared with diluted acetic or hydrochloric acid. They were evaluated by the lowering of the blood glucose concentration in rabbits. The systemic absorption of insulin from the device can be enhanced by using a 5% or higher concentration of acetic acid solution as well as 1% HCl solution. The results indicate that the proposed device prepared with up to 30% of acetic acid solution produced no eye irritation. A single device containing 0.2 mg of insulin is sufficient to control the blood glucose levels in a uniform manner (60% of initial) for over 8 h.

Absorption↗