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Biomedical subjects

J T Lee

Publications and source records attributed to J T Lee.

At least 73 records · Page 4Linked to original sources
PubMed2000

Focal lesions in cirrhotic liver: comparing MR imaging during arterial portography with Gd-enhanced dynamic MR imaging.

The purpose of this study was to document the additional value of MR imaging during arterial portography (MRAP) in patients examined with intravenous contrast-enhanced dynamic MR imaging for the assessment of focal lesions in patients with cirrhosis or chronic viral hepatitis. The MR images of 24 patients with 39 hepatocellular carcinomas and 18 benign hepatocellular nodules examined with dynamic MR imaging and MRAP within a 14-day interval were retrospectively reviewed. For 39 hepatocellular carcinomas, MRAP revealed 37 perfusion defects (95%), while dynamic MR imaging demonstrated 35 occurrences of nodular contrast-enhancement (90%) on arterial dominant phases. Among the 11 benign nodules misinterpreted as hepatocellular carcinoma due to their high signal intensities on arterial-dominant phases of dynamic MR imaging, eight (73%) showed intratumoral portal venous perfusion on MRAP and were regarded as benign nodules. As a result of its high sensitivity and its potential ability to enable differentiation of benign and malignant hepatocellular nodules, MRAP can be added to dynamic MR imaging for planning future management in patients with equivocal hepatocellular nodules in the cirrhotic liver.

Adult↗
PubMed1999

Further examination of the Xist promoter-switch hypothesis in X inactivation: evidence against the existence and function of a P(0) promoter.

The onset of X inactivation coincides with accumulation of Xist RNA along the future inactive X chromosome. A recent hypothesis proposed that accumulation is initiated by a promoter switch within Xist. In this hypothesis, an upstream promoter (P(0)) produces an unstable transcript, while the known downstream promoter (P(1)) produces a stable RNA. To test this hypothesis, we examined expression and half-life of Xist RNA produced from an Xist transgene lacking P(0) but retaining P(1). We confirm the previous finding that P(0) is dispensable for Xist expression in undifferentiated cells and that P(1) can be used in both undifferentiated and differentiated cells. Herein, we show that Xist RNA initiated at P(1) is unstable and does not accumulate. Further analysis indicates that the transcriptional boundary at P(0) does not represent the 5' end of a distinct Xist isoform. Instead, P(0) is an artifact of cross-amplification caused by a pseudogene of the highly expressed ribosomal protein S12 gene Rps12. Using strand-specific techniques, we find that transcription upstream of P(1) originates from the DNA strand opposite Xist and represents the 3' end of the antisense Tsix RNA. Thus, these data do not support the existence of a P(0) promoter and suggest that mechanisms other than switching of functionally distinct promoters control the up-regulation of Xist.

Animals↗
PubMed1999

Phase II clinical trial of SKI-2053R, a new platinum analog, in the treatment of patients with advanced gastric adenocarcinoma.

BACKGROUND: SKI-2053R (SK Chemicals, Kyungki-Do, South Korea) is a new platinum derivative with antitumor activity against various cell lines, including cisplatin-resistant tumor cell lines. Preclinical studies have suggested that it is less nephrotoxic than cisplatin. This study evaluated the efficacy and toxicity of SKI-2053R in the treatment of patients with advanced gastric adenocarcinoma. METHODS: Thirty-seven patients with advanced gastric adenocarcinoma that was unresectable or metastatic were treated. No prior chemotherapy or radiotherapy was allowed. Patients received SKI-2053R 360 mg/m(2) by 1-hour infusion on Day 1. After the first cycle, subsequent doses were adjusted according to the toxicity. Courses were repeated every 28 days. RESULTS: Thirty-five patients were evaluable for response and toxicity. Six patients achieved a major response (17%; 95% confidence interval, 8-33%); 2 were complete and 4 were partial responses. The median duration of response was 7.2 months, with a range of 1-20 months. Patients could tolerate the treatment without significant toxicity. No patients had Grade 3 or 4 toxicity. The most frequent toxicity was Grade 1 or 2 proteinuria (26% of cycles), but it was mild and transient. Leukopenia, thrombocytopenia, azotemia, nausea and vomiting, and neurotoxicity were not frequent. These low toxicity profiles indicated that the dose of SKI-2053R could be increased in future studies. CONCLUSIONS: SKI-2053R was active in the treatment of patients with gastric adenocarcinoma and had favorable toxicity profiles.

Adenocarcinoma↗
PubMed1999

Targeted mutagenesis of Tsix leads to nonrandom X inactivation.

During X inactivation, mammalian female cells make the selection of one active and one inactive X chromosome. X chromosome choice occurs randomly and results in Xist upregulation on the inactive X. We have hypothesized that the antisense gene, Tsix, controls Xist expression. Here, we create a targeted deletion of Tsix in female and male mouse cells. Despite a deficiency of Tsix RNA, X chromosome counting remains intact: female cells still inactivate one X, while male cells block X inactivation. However, heterozygous female cells show skewed Xist expression and primary nonrandom inactivation of the mutant X. The ability of the mutant X to block Xist accumulation is compromised. We conclude that Tsix regulates Xist in cis and determines X chromosome choice without affecting silencing. Therefore, counting, choice, and silencing are genetically separable. Contrasting effects in XX and XY cells argue that negative and positive factors are involved in choosing active and inactive Xs.

Animals↗
PubMed1999

Frequency of sister chromatid exchange in chrysotile-exposed workers.

Chrysotile, which is an industrial carcinogen, has been shown to induce a dose-dependent increase in the frequency of sister chromatid exchange (SCE) in vitro. Authors designed this study to examine the increase of SCEs frequency in the workers occupationally exposed to chrysotile. Heparinized whole blood samples from 45 chrysotile-exposed and 45 control volunteers were cultured for 72 h. The significant difference of SCE frequency was found between chrysotile-exposed workers and control group. The highest SCEs frequency was found in chrysotile-exposed smokers, and the lowest in control non-smokers. The effect of chrysotile exposure on SCEs was marginally significant after controlling the effects of age and smoking by multiple regression analysis.

Adult↗
PubMed1999

Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain.

Dosage compensation in mammals occurs by X inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic). In response to developmental cues, the Xic orchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up the Xic. We previously showed that the Xic is contained within a 450-kb sequence that includes Xist, an RNA-encoding gene required for X inactivation. To characterize the Xic further, we performed deletional analysis across the 450-kb region by yeast-artificial-chromosome fragmentation and phage P1 cloning. We tested Xic deletions for cis inactivation potential by using a transgene (Tg)-based approach and found that an 80-kb subregion also enacted somatic X inactivation on autosomes. Xist RNA coated the autosome but skipped the Xic Tg, raising the possibility that X chromosome domains escape inactivation by excluding Xist RNA binding. The autosomes became late-replicating and hypoacetylated on histone H4. A deletion of the Xist 5' sequence resulted in the loss of somatic X inactivation without abolishing Xist expression in undifferentiated cells. Thus, Xist expression in undifferentiated cells can be separated genetically from somatic silencing. Analysis of multiple Xic constructs and insertion sites indicated that long-range Xic effects can be generalized to different autosomes, thereby supporting the feasibility of a Tg-based approach for studying X inactivation.

Acetylation↗
PubMed1999

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.

Adult↗
PubMed1999

Separation of enantiomers by capillary electrophoresis using pentosan polysulfate.

Pentosan polysulfate, a semisynthetic polysaccharide, was employed as a chiral run buffer additive in capillary electrophoresis. Twenty-eight racemic analytes were resolved. The separations were successful only at low pH when the analytes were significantly protonated. This suggests that ionic interactions were the dominant associative interactions between the anionic pentosan polysulfate and the positively charged analytes. Compared to other linear, carbohydrate-based chiral selectors (i.e., chondroitin sulfates, heparin and dextran sulfate) pentosan polysulfate has some characteristics common of anionic polysaccharides; yet it has several differences in its structure and properties which account for its unusual enantioselectivity. The effects of pH, concentration of phosphate buffer, concentration of pentosan polysulfate and the type and concentration of organic modifier on the enantiomeric separations were investigated. The optimization of these separations were dependent on the nature of the analytes and could be achieved by the proper choice of experimental conditions.

Buffers↗
PubMed1999

Stability and cytotoxicity of Fab-ricin A immunotoxins prepared with water soluble long chain heterobifunctional crosslinking agents.

The effects of the hindered and non-hindered water soluble long-chain disulfide bonds on the stability and cytotoxicity of the ricin A chain (RTA) immunotoxin were examined. The RTA immunotoxins were prepared with the Fab fragments of anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody (Fab-RTA) using sulfosuccinimidyl-6-[(-methyl-(-(2-pyridyldithio)toluamido]hexanoate (S-LC-SMPT) and sulfosuccinimidyl-6-[3-(2-pyridyldithio)-propionamido]hexanoate (S-LC-SPDP). The prepared Fab-RTA immunotoxins were evaluated for their conjugation yield, immunoreactivity, thermal and disulfide bond stability and cytotoxicity. The conjugation yield of the Fab-RTA immunotoxin from the water soluble long chain crosslinking agents, S-LC-SMPT and S-LC-SPDP, were comparable. Both Fab-RTA immunotoxins exhibited a similar immunoreactivity and thermal stability in aqueous solution. However, S-LC-SMPT -mediated Fab-RTA, sterically hindered, showed an enhanced disulfide bond stability in vitro over S-LC-SPDP mediated one. In the cytotoxicity against antigenic cell Daudi, the S-LC-SMPT -mediated RTA immunotoxin maintained a comparable cytotoxicity, compared with S-LC-SPDP mediated Fab-RTA immunotoxin.

Animals↗
PubMed1999

Isolation, characterization, and stability of positional isomers of mono-PEGylated salmon calcitonins.

PURPOSE: To separate and characterize the different positional isomers of mono-PEGylated salmon calcitonins (mono-PEG-sCTs) and to evaluate the effects of the PEGylation site on the stability of different mono-PEG-sCTs in rat kidney homogenate. METHODS: Mono-PEG-sCTs were prepared using succinimidyl carbonate monomethoxy polyethylene glycol (5,000 Da) and separated by gel-filtration HPLC followed by reversed-phase HPLC. To characterize PEGylated sCTs, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) and reversed-phase HPLC of the trypsin digested samples were performed. Mono-PEG-sCTs and sCT in rat kidney homogenates were measured by column-switching reversed-phase HPLC with on-line detection of the radioiodinated samples using a flow-through radioisotope detector. RESULTS: Three different mono-PEGylated sCTs were separated by reversed-phase gradient HPLC. From the MALDI-TOF MS analysis, the average molecular weight of mono-PEG-sCTs was confirmed as around 8650 Da. The presence of PEG moiety in the mono-PEG-sCTs was also manifested by the fact that the distance between two adjacent mass spectum lines was 44 Da which corresponds to PEG monomer unit. Tryptic digestion analysis demonstrated that these mono-PEG-sCTs are 3 positional isomers of N-terminus, Lys18- and Lys11-residue modified mono-PEGylated sCTs. The degradation half-life of these 3 positional isomers in rat kidney homogenates significantly increased in order of the N-terminus (125.5 min), Lys11- (157.3 min), and Lys18 residue modified mono-PEGylated sCT (281.5 min) over the native sCT (4.8 min). CONCLUSION: Three positional isomers of mono-PEGylated sCTs were purified and characterized. Of these, the resistance to proteolytic degradation was highest for the Lys18-residue modified mono-PEG-sCT. These studies demonstrate that the in vivo stability of PEGylated sCTs is highly dependent on the site of PEG molecule attachment.

Amino Acid Sequence↗
PubMed1999

Tsix, a gene antisense to Xist at the X-inactivation centre.

In mammals, dosage compensation is achieved by X inactivation and is regulated in cis by the X-inactivation centre (Xic) and Xist. The Xic controls X-chromosome counting, choice of X to inactivate and initiation of silencing. Xic action culminates in a change in Xist RNA property from a scarce, unstable RNA to highly expressed Xist RNA that coats the future inactive X. Deleting a 65-kb region downstream of Xist results in constitutive Xist expression and X inactivation, implying the presence of a cis-regulatory element. In this region, we now report the discovery of a gene antisense to Xist. Tsix is a 40-kb RNA originating 15 kb downstream of Xist and transcribed across the Xist locus. Tsix sequence is conserved at the human XIC. Tsix RNA has no conserved ORFs, is seen exclusively in the nucleus and is localized at Xic. Before the onset of X inactivation, Tsix is expressed from both X chromosomes. At the onset of X inactivation, Tsix expression becomes monoallelic, is associated with the future active X and persists until Xist is turned off. Tsix is not found on the inactive X once cells enter the X-inactivation pathway. Tsix has features suggesting a role in regulating the early steps of X inactivation, but not the silencing step.

Animals↗
PubMed1999

Preparation and characterization of polyethylene-glycol-modified salmon calcitonins.

The conjugation of salmon calcitonin (sCT) by covalent linkage of polyethylene glycol (PEG) was attempted to overcome several disadvantages of sCT as a therapeutic drug, namely its rapid clearance from blood circulation and enzymatic degradation. The polymer employed was succinimidyl carbonate monomethoxypolyethylene glycol (12 kDa). Superose HR size-exclusion chromatography was applied to separate the PEGylated sCTs (mono-PEG-sCT and di-PEG-sCT) from the unmodified sCT. The PEGylation of sCT was verified by an electrophoresis gel stained with iodine and by MALDI-TOF mass spectrometry. The molecular weights of mono-PEG-sCT and di-PEG-sCT were determined to be 16,094 and 29,077 Da, respectively. PEGylated sCTs showed a substantially improved stability in rat liver homogenates as compared to the intact sCT, indicating that PEG molecules protected sCT from various degrading enzymes. These PEGylated sCTs exhibited similar biological activity to the intact sCT by adenosine cyclic 3',5'-phosphate (cAMP) assay. In clearance studies in the rat, PEGylated sCTs had significantly longer circulating half-lives than the intact sCT (11.2 min for mono-PEG-sCT and 54.0 min for di-PEG-sCT versus 4.7 min for intact sCT).

Amino Acid Sequence↗
PubMed1999

Not just another guideline.

Explore the source record for details and available documents.

Centers for Disease Control and Prevention, U.S.↗
PubMed1999

Phase transitions of colloid-polymer systems in two dimensions.

Phase transitions of systems consisting of colloidal particles and non-adsorbing polymer in a solvent are studied theoretically in two dimensions. The colloids are modeled as hard spheres and the polymer as an ideal gas. The imbalance in osmotic pressure induced by the depletion effect gives rise to an effective attraction tail for the colloid-colloid interaction. For a monodisperse polymer, liquid-liquid separation is predicted to occur for appropriate colloid concentrations when the ratio s of the radius of gyration of the polymer to the radius of the colloidal particle is greater than 0.31, while solid-liquid separation is predicted to occur for all colloid concentrations when s is smaller than 0.31. Polydispersity of polymer is found to increase the extent of liquid-liquid coexistence, and when the average s is smaller than 0.31, and for appropriate colloid concentrations, liquid-liquid coexistence occurs provided the polymer size distribution is broad enough. Partitioning and size distribution of polymer in coexisting phases are also predicted.

Journal Article↗
PubMed1999

Air pollution and daily mortality in Seoul and Ulsan, Korea.

The relationship between air pollution and daily mortality for the period 1991-1995 was examined in two Korean cities, Seoul and Ulsan. The observed concentrations of sulfur dioxide (SO2; mean = 28.7 ppb), ozone (O3; mean = 29.2 ppb), and total suspended particulates (TSP; mean = 82.3 microg/m3) during the study period were at levels below Korea's current ambient air quality standards. Daily death counts were regressed separately in the two cities, using Poisson regression on SO2, O3, and/or TSP controlling for variability in the weather and seasons. When considered singly in Poisson regression models controlling for seasonal variations and weather conditions, the nonaccidental mortality associated with a 50-ppb increment in a 3-day moving average of SO2 concentrations, including the concurrent day and the preceding 2 days, was 1.078 [95% confidence interval (CI), 1.057-1.099] for Seoul and 1.051 (CI, 0.991-1.115) for Ulsan. The rate ratio was 1.051 (CI, 1.031-1.072) in Seoul and 0.999 (CI, 0. 961-1.039) in Ulsan per 100 microg/m3 for TSP, and 1.015 (CI, 1. 005-1.025) in Seoul and 1.020 (0.889-1.170) in Ulsan per 50 ppb for 1-hr maximum O3. When TSP was considered simultaneously with other pollutants, the TSP association was no longer significant. We observed independent pollution effects on daily mortality even after using various approaches to control for either weather or seasonal variables in the regression model. This study demonstrated increased mortality associated with air pollution at both SO2 and O3 levels below the current World Health Organization recommendations.

Air Pollutants↗
PubMed1999

Reanalysis of the effects of air pollution on daily mortality in Seoul, Korea: A case-crossover design.

We used the case-crossover design to identify any increase in mortality in Seoul, Korea, when there were higher levels of ambient air pollution on case-days than would be expected solely as a result of chance. This empirical study showed that either unidirectional retrospective (selecting only control days prior to death) or prospective (selecting only control days after death) control sampling could cause risk estimates to be confounded by seasonal waves as well as time trends in air pollution levels. In bidirectional control sampling in which exposures at death were compared with exposures both before and after death, the estimated mortality was resistant to confounding by time patterns of air pollution. Using a bidirectional control sampling approach, the results from a conditional logistic regression model controlling for weather conditions showed that the nonaccidental mortality associated with a 50-ppb increment over a 3-day moving average of SO(2) concentrations, including the concurrent day and preceding 2 days, was 1.023 [95% confidence interval (CI), 1.016-1.084]. The relative risk of death was 1.023 (CI, 0.999-1.048) per 50 ppb for 1-hr maximum O(3) and 1.010 (CI, 0.988-1.032) per 100 microg/m(3 )or total suspended particulates. In conclusion, the findings of this study were 2-fold: given the consistency of the observed association between SO(2) and daily mortality across different analysis methods, the association reported here indicates that air pollution is a probable contributor to premature death; and bidirectional control sampling is needed in a case-crossover design applied to air pollution epidemiologic studies to control confounding by seasonal patterns of air pollution as well as time trends.

Adolescent↗
PubMed1999

Contrast enhancement of small hepatocellular carcinoma: usefulness of three successive early image acquisitions during multiphase dynamic MR imaging.

OBJECTIVE: The purpose of this study was to document the usefulness of early triphasic image acquisition during gadolinium-enhanced multiphase dynamic MR imaging for the detection of contrast enhancement in small hepatocellular carcinoma. SUBJECTS AND METHODS: Dynamic MR imaging was performed in 332 patients at 1.5 T using a T1-weighted fast low-angle shot sequence (TR range/TE, 113-130/4.1; flip angle, 80 degrees). With the start of bolus injection of gadolinium dimeglumine (0.1 mmol/kg) into the antecubital vein, three sets of contrast-enhanced images of the entire liver were obtained serially at 10, 35, and 60 sec. Contrast enhancement of the tumor detected on each phase was evaluated in conjunction with the unenhanced T1-weighted images for 52 patients with small hepatocellular carcinomas up to 2 cm in diameter (n = 79). RESULTS: The first phase images depicted a larger number (n = 57) of contrast enhancement of small hepatocellular carcinoma tumors than the second (n = 44) or third phase images (n = 14). Twenty-six lesions were enhanced only during the first phase, and nine, during the second phase. The detection rate of contrast enhancement in the combination of first and second phases was the same as the overall detection rate for all three phases (70/79, 89%) and significantly higher than those of each phase. CONCLUSION: Early multiple image acquisition is helpful for the assessment of small hepatocellular carcinoma and is enabled by the high detection rate of contrast enhancement regardless of individual variations in the timing of enhancement.

Carcinoma, Hepatocellular↗