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Biomedical subjects

J T Lee

Publications and source records attributed to J T Lee.

At least 19 recordsLinked to original sources
PubMed1997

Long-range cis effects of ectopic X-inactivation centres on a mouse autosome.

In mammals, the X chromosome is unique in being capable of complete inactivation. Such X inactivation evolved to compensate for gene dosage differences between females with two X chromosomes and males with one. Transcriptional silencing of a single female X chromosome is controlled in cis by Xist, whose RNA product coats the inactive X chromosome (Xi), and the X-inactivation centre (Xic). A transgenic study limited the Xic to 450 kilobases including Xist, and demonstrated that it is sufficient to initiate X inactivation. Here we report that ectopic Xist RNA completely coats transgenic chromosome 12. Expression of genes over 50 centimorgans was reduced two-fold and was detected only from the normal homologue in fibroblasts. Moreover, ectopic Xic action resulted in chromosome-wide changes that are characteristic of the X(i): DNA replication was delayed, and histone H4 was markedly hypoacetylated. Our findings suggest long-range cis effects on the autosome similar to those of X inactivation, and imply that the Xic can both initiate X inactivation and drive heterochromatin formation. Thus, the potential for chromosome-wide gene regulation is not intrinsic to X-chromosome DNA, but can also occur on autosomes possessing the Xic.

Acetylation↗
PubMed1997

Nodular hepatocellular carcinomas: detection with arterial-, portal-, and delayed-phase images at spiral CT.

PURPOSE: To evaluate the effectiveness of three-phase spiral computed tomography (CT) for the evaluation of nodular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Images obtained at three-phase spiral CT in 45 patients with 81 nodular HCCs were reviewed. Images were obtained with 10-mm collimation and 10 mm/sec table speed during intravenous administration of 2 mL/kg 68% nonionic contrast material at a rate of 3 mL/sec. Hepatic arterial-phase (AP), portal-phase (PP), and delayed-phase (DP) images were obtained 25-30 seconds, 60-70 seconds, and 300 seconds, respectively, after injection of the contrast material. Lesion detectability and conspicuity were compared among these three protocols by two readers. RESULTS: The AP images depicted a statistically significantly larger number of lesions (n = 67), although the differences in the number of lesions depicted between the PP and DP images were not statistically significant. Twenty-one lesions were detected only with the AP images, three with the PP images, and seven with the DP images. The most clearly visualized lesions were most commonly depicted on the AP images (n = 47) rather than the PP images (n = 11) or the DP images (n = 23). CONCLUSION: Lesion detection and conspicuity were best with the AP images. However, some lesions were detected only with the DP and PP images, so that maximum lesion visualization is achieved by using all three phases.

Adult↗
PubMed1996

A method for high efficiency YAC lipofection into murine embryonic stem cells.

We describe a modified protocol for introducing yeast artificial chromosomes (YACs) into murine embryonic stem (ES) cells by lipofection. With a decreased DNA:cell ratio, increased concentration of condensing agents and altered culture conditions, this protocol reduces the requirement for YAC DNA to a few micrograms, improves the recovery of neomycin-resistant ES colonies and increases the yield of clones containing both flanking vector markers and insert. These modifications enable generation of sufficient 'intact' transgenic clones for biological analysis with a single experiment.

Animals↗
PubMed1996

A 450 kb transgene displays properties of the mammalian X-inactivation center.

X inactivation results in inactivation of one X chromosome to compensate for gene dosage differences between mammalian females and males. It requires the X-inactivation center (Xic) and Xist in cis. We report that introducing 450 kb of murine Xic/Xist sequences onto autosomes activates female dosage compensation in male ES cells. Xist is induced upon differentiation and can be expressed from both endogenous and ectopic loci, suggesting that elements for counting and choosing Xs are present in the transgene. Differentiating transgenic ES cells undergo excessive cell death. Postnatally, Xist is expressed only from the transgene. Ectopic Xist RNA structurally associates with the autosome and may inactivate a marker gene in cis. These results argue that the Xic is contained within 450 kb and that these sequences are sufficient for chromosome counting, choosing, and initiation of X inactivation.

Animals↗
PubMed1996

Panencephalitic Creutzfeldt-Jakob disease. Unusual presentation of magnetic resonance imaging and proton magnetic resonance spectroscopy.

We present serial magnetic resonance imaging (MRI) scans on a biopsy-verified case of Creutzfeldt-Jakob disease (CJD). The initial MRI scan demonstrated increased T2 signal-intensity within the basal ganglia and thalami. Subsequent MRI scans demonstrated a thin cortex, increased T2 signals diffusely within the white matter including U-fibers, and hypointense T2 signals within the basal ganglia, and thalami. Proton magnetic resonance spectroscopy (1H-MRS) study showed an absence of creatine, choline and N-acetylaspartate signals. By these characteristic findings, serial MRI and MRS studies may be helpful in differentiating CJD from other dementing illnesses.

Biopsy↗
PubMed1996

A review of new oncotropic tracers for PET imaging.

We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease.

Animals↗
PubMed1996

Synchronous non-small cell lung cancers.

INTRODUCTION: The few series of synchronous lung cancers have included small cell and carcinoid tumors. We wished to determine the prognosis for patients with synchronous non-small cell lung cancer (NSCLC). METHODS: A database of 3034 lung cancer patients was reviewed for synchronous NSCLC. Survival was determined by Kaplan-Meier method and compared by log-rank analysis. RESULTS: There were 27 patients (0.8%). Fourteen were completely resected (CR) and had a 5-year survival rate of 45% The 5-year survival rate for patients whose highest stage tumor was stage I or II was 38%, versus 0% for patients whose highest tumor stage of III (P = 0.01). The 5-year survival rate for patients with two stage I tumors was 41% versus 0% for patients with 2 stage III tumors (P = 0.03). The 5-year survival rate for patients treated with wedge resections was similar to that for patients treated with lobectomies or pneumonectomy (L/P). CONCLUSIONS: We conclude that the prognosis for patients with synchronous NSCLC may not be dismal if both tumors are resectable and stage I or II. Wedge resections are an alternative for those who cannot tolerate L/P.

Adolescent↗
PubMed1996

Surgical outcome information and the media.

There is increased media attention to healthcare outcome in the current reform atmosphere. Surgical care is a natural target for both print and electronic coverage. Hospital public relations departments often will be the interface with media representatives. Because surgical care outcome interpretation requires thoughtful evaluation of both single-patient and grouped-patient data, as well as knowledge of realistic risk-benefit ratios, it always is prudent to work with your local surgeon when the request for a story comes to the public relations department.

Hospitals↗
PubMed1996

Isolation and characterization of gangliosides from Theileria sergenti.

The gangliosides of Theileria sergenti piroplasms were isolated and analyzed by thin-layer chromatography (TLC) and TLC immunostaining test. Four species of gangliosides, designated as G-1, G-2, G-3, and G-4, were separated on TLC. G-1, G-2, G-3, and G-4 ganglioside showed the same mobility as GM3, sialosylparagloboside (SPG), i-active ganglioside, and I-active ganglioside on the TLC plate, respectively. In order to characterize the molecular species of gangliosides from T. sergenti, G-1, G-2, G-3, and G-4 gangliosides were purified and tested by TLC immunostaining test with monoclonal antibodies against gangliosides. G-1 ganglioside had reactivity to anti-GM3 monoclonal antibody. G-2 gave reaction with monoclonal antibody to SPG containing N-glycolylneuraminic acid (NeuGc). G-3 showed reactivity to the anti-i-active ganglioside (NeuGc) monoclonal antibody. G-4 was recognized by the monoclonal antibody which reacts with I-active ganglioside (NeuGc). In addition, sialic acid moiety of the gangliosides from T. sergenti piroplasms was also analyzed. N-acetylneuraminic acid-containing gangliosides were hardly detectable in T. sergenti piroplasms. Gangliosides from T. sergenti (G-1, G-2, G-3, and G-4) carried only NeuGc as their sialic acid moiety. These results suggest that G-1, G-2, G-3, and G-4 gangliosides are GM3 (NeuGc) [NeuGc alpha 2-3Gal beta 1-4Glc beta 1-Cer], SPG (NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], i-active ganglioside (NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], and I-active ganglioside(NeuGc) [NeuGc alpha 2-3Gal beta 1-4GlcNAc beta 1-3 (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6) Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer], respectively.

Anemia↗
PubMed1996

Efficacy of in vitro treatment of chronic myelogenous leukemia cell line, K562 cells, using 4-hydroperoxycyclophosphamide, alpha-interferon and gamma-interferon.

Alpha-interferon (alpha-IFN) and gamma-interferon (gamma-IFN) are highly effective biologic agents in the treatment of chronic myelogenous leukemia (CML). 4-hydroperoxycyclophosphamide (4-HC) is the most commonly used chemotherapeutic drug when purging bone marrow contaminated with malignant cells. To investigate the efficacy of alpha-IFN, gamma-IFN and 4-HC as purging agents in CML patients, K562 cells, a human CML cell line, were treated in vitro with these drugs singly or in combination. The cytotoxic effect was evaluated by MTT assay. Data were analyzed for synergism by the median effect principle of Chou and Talalay. Using Southern blot analysis, the effect of purging on the suppression of bcr gene rearrangement was also evaluated. Alpha-IFN, gamma-IFN and 4-HC all showed good concentration-dependent cytotoxic effect. Median cytotoxic doses of alpha-IFN gamma-IFN and 4-HC were 0.03 microM 0.20 microM and 1.97 microM respectively, and molar ratios of median doses of alpha-IFN to 4-HC, gamma-IFN to 4-HC and alpha-IFN to gamma-IFN were 1:80, 1:10 and 1:8, respectively. The combination treatment of alpha-IFN and 4-HC, and gamma-IFN and 4-HC showed significant synergistic cytotoxic activities, but combination of alpha-IFN and gamma-IFN was antagonistic. Status of bcr gene rearrangements in K562 cells was not changed after the treatments. Our results appear to provide an efficient method for removing CML cells from the bone marrow of CML patients.

Antineoplastic Agents↗
PubMed1995

Biodistribution of 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragments in nude mice with interleukin 2 alpha receptor-positive tumor xenografts.

We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4-([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of 18F-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both preparations was rapid, with < 10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431 tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [125I]iodide and predominantly N-epsilon-[18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled dsFv.

Animals↗
PubMed1995

Detection of malignant melanoma by Tc-99m HMPAO.

A number of radiopharmaceutical agents have been evaluated for the detection of malignant melanoma. Because anamine is necessary for melanin synthesis, melanotic tumors may possess numerous amine receptors. Tc-99m HMPAO consists of macrocyclic amine radicals. The purpose of this study was to evaluate Tc-99m HMPAO as an effective agent for localizing malignant melanomas on the radioisotope imaging. Six patients, with malignant melanomas were studied. Tc-99m HMPAO SPECT images were obtained in all patients. SPECT was used for the localization of the primary focus, and whole body scans were used for the evaluation of unexpected metastatic lesions. The results were compared with MRI and CT. Tc-99m HMPAO SPECT revealed a high correlation with CT and MRI for the primary focus. Abnormally increased activity at the unexpected metastatic lymph nodes in two patients were also noticed. This was confirmed by CT and MRI for those sites. Tc-99m HMPAO appears to be a useful agent for the localization of both the primary focus and unexpected metastatic lesion in patients with malignant melanoma.

Aged↗
PubMed1995

Evaluation of embolization effect of hepatocellular carcinoma by hepatic arterial flow study with Tc-99m MAA SPECT.

The degree of hepatocellular carcinoma vascularity in eight patients was assessed with Tc-99m MAA radionuclide angiography before and after treatment. For chemoembolization therapy, lipiodol and doxorubicin hydrochloride were administered intraarterially along with Gelfoam particles. The ratio of radioactivity in the hepatocellular carcinoma compared to that in the surrounding uninvolved tissue before therapy was 6.5-19.0 with a mean of 12.0. After therapy, the ratio dropped to 0.5-1.3. Because survival improved significantly after the therapeutic regimen used in these patients, radionuclide Tc-99m MAA angiography appears to be an accurate method for demonstrating successful embolization of the vascular supply in hepatocellular carcinoma.

Adult↗
PubMed1995

A randomized, double-blind, placebo-controlled, dose-ranging study of dofetilide in patients with inducible sustained ventricular tachyarrhythmias.

INTRODUCTION: Dofetilide is a new antiarrhythmic agent with potent IK blocking properties in vitro. We developed a dose-ranging, placebo-controlled study design to define the range of effective doses and to evaluate the clinical electrophysiology of intravenous dofetilide in patients in whom sustained ventricular tachycardia or fibrillation was reproducibly inducible at baseline electrophysiologic testing. METHODS AND RESULTS: The initial four patients received low doses that were increased in subsequent groups of four if adverse effects were absent. In each group of four patients, one patient was randomly assigned to placebo (double blind). Twenty-four patients were studied at six incremental loading and maintenance infusion regimens. Dofetilide (0.1 to 8.0 ng/mL) produced concentration-related increases in the % delta of QT (r = 0.79, P < 0.001), QTc (r = 0.60, P = 0.02), RR (r = 0.62, P < 0.02), and right ventricular effective refractory period (cycle length 600 msec; r = 0.68, P = 0.04). Placebo produced no changes in any of these measurements. Sustained ventricular tachycardia or ventricular fibrillation was no longer inducible in 1 of 6 patients receiving placebo and 8 of 18 receiving dofetilide (4 to 13 sec nonsustained ventricular tachycardia was induced in 4 of these 8). One patient developed torsades de pointes at a high concentration (5.3 ng/mL). CONCLUSIONS: We conclude that: (1) dofetilide produces concentration-related IK blocking effects in patients; (2) an incremental dose-ranging study design aids in identifying the range of doses demonstrating electrophysiologic effects and efficacy; (3) a concomitant placebo group provides important data to assess reproducibility of results over time; and (4) further studies of dofetilide's efficacy and toxicity should be conducted.

Adolescent↗