Design and synthesis of the G-quadruplex-specific cleaving reagent perylene-EDTA.iron(II).
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Animals↗
Biomedical subjects
J T Lee
Publications and source records attributed to J T Lee.
Primary aortoenteric fistula: computed tomographic diagnosis of an atypical presentation.
A primary aortoenteric fistula is a potentially devastating complication of untreated aortic aneurysmal disease. The clinical presentation can be confusing, leading to a delay in diagnosis. Computed tomography (CT) can greatly assist in establishing the diagnosis. An unusual case of a primary aortoenteric fistula with an atypical presentation is described. The patient presented with symptoms indicating an exacerbation of recurrent nephrolithiasis. No clinical history of an abdominal aortic aneurysm or previous history of gastrointestinal hemorrhage was reported. A CT scan demonstrated extravasation of arterial contrast into the duodenum. The aorta was repaired with an in-line prosthetic graft. A review of the literature regarding this rare entity and surgical options are presented.
Aged↗
Sepharose-unbinding ricin E as a source for ricin A chain immunotoxin.
To evaluate the Sepharose-unbinding ricin E as a preference source material for ricin A chain (RTA) in immunotoxin studies, RTA of ricin E (RTA(E)) was characterized and compared with RTA of the Sepharose-binding ricin D (RTA(D)). RTA(E) and RTA(D) were separated into two subunits of A(1) and A(2) by capillary electrophoresis. The isoelectric points of A(1) and A(2) subunits were determined to be 7.6 and 7.4, respectively, for RTA(E), while they were 7.4 and 7.3, respectively, for RTA(D). The molecular masses of A(1) and A(2) isomers determined by the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry were 31059 and 32266 Da, respectively, for RTA(E), while they were 30892 and 32179 Da, respectively, for RTA(D). There were no significant differences in the cell surface affinity and cytotoxicity between RTA(E) and RTA(D). Anti-CD4-RTA(E) immunotoxin was prepared by conjugating RTA(E) with anti-CD4 monoclonal antibody using a heterobifunctional crosslinker, 4-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene. Anti-CD4-RTA(E) immunotoxin showed comparable cytotoxic effects to anti-CD4-RTA(D) immunotoxin to antigen-positive CEM cells in vitro. It is concluded that RTA(E) from ricin E is one of different variants of RTA(D) and may be used as a preference source material of RTA in immunotoxin studies.
Animals↗
Targeting sites for conservation: using a patch-based ranking scheme to assess conservation potential.
Rare habitats are increasingly threatened by fragmentation and measures are required to conserve these valuable resources. Here, we present a method of targeting habitat patches for conservation using a Geographical Information System. We ranked patches of chalk grassland in the Chiltern Hills Area of Outstanding Natural Beauty using simple abiotic criteria, namely: patch area, patch shape, proximity to areas of the same habitat and surrounding land-use type. We compiled a regionally specific list of indicator species and ranked the habitat patches based on their alpha diversity (calculated from species richness). We compared the results of the two ranking schemes and identified key aggregations of the existing reserve network. These could form the basis of future habitat expansion as required by the United Kingdom Biodiversity Action Plan.
Animals↗
Use of solvents in industries in Korea: experience in Sinpyeong-Jangrim industrial complex.
OBJECTIVES: To identify the most popular solvent and typical type of solvent work among solvent-using workplaces in Korea. METHODS: In practice, 862 solvent-using workshops in Sinpyeong-Jangrim industrial complex in Pusan were investigated in a 2-year period from March 1995 to February 1997. Solvent vapors in the breathing zone of workers were collected by personal sampling with charcoal tubes. The exposed charcoal was extracted with carbon disulfide, and the solvents in the extract were analyzed by flame ionization detector-equipped gas chromatography (FID-GC). RESULTS: Solvents were used in painting, glue application, cleaning, printing and solvent-mixing workshops in decreasing order of popularity. Toluene was the most frequently measured solvent. In the five types of solvent work, acetone, hexane, methyl ethyl ketone, methyl isobutyl ketone, tetrachloroethylene, trichloroethylene and xylenes were also used frequently. CONCLUSIONS: Toluene was identified as the most frequently used solvent in solvent works in Korean manufacture industries in the late 1990s. Eight types of solvent were popularly used in five popular types of solvent work. These trends are very similar to the cases reported for industries in Japan.
Adhesives↗
Synergistic effects of pi3k/akt on abrogation of cytokine-dependency induced by oncogenic raf.
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Animals↗
Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation.
In mammals, X-chromosome inactivation (XCI) ensures equal expression of X-linked genes in XX and XY individuals by transcriptionally silencing one X-chromosome in female cells. In this review, we discuss an imprinted form of X-inactivation in which the paternal X (Xp) is preferentially silenced. Believed to be the ancestral mechanism of dosage compensation in mammals, imprinted X-inactivation can still be observed in modern-day marsupials and in the extraembryonic tissues of some eutherians such as the mouse. Recent experiments have addressed the nature of the gametic imprint and focused on the regulatory interaction between the noncoding RNA gene, Xist, and its antisense partner, Tsix. Our review of the literature has inspired an unconventional view of imprinted XCI in mice. First, the evidence strongly argues that imprinted XCI is inabsolute, so that a stochastic number of extraembryonic cells escape imprinting. Second, contrary to conventional thinking, we would like to consider the possibility that the paternal X might actually be transmitted to the zygote as a pre-inactivated chromosome. In this model, the gamete initiates and establishes imprinted XCI, while the zygote maintains the pre-established pattern of gametic inactivation. Finally, we hypothesize that the inabsolute nature of imprinting is caused by imperfect zygotic maintenance. We propose that the mouse represents a transitional stage in the evolution of random XCI from an absolutely imprinted mechanism.
Animals↗
Effects of inducible MEK1 activation on the cytokine dependency of lymphoid cells.
The Raf/MEK/MAP kinase cascade plays a critical role in transducing growth signals from activated cell surface receptors. Using deltaMEK1:ER, a conditionally active form of MEK1, we demonstrate the ability of this dual specificity protein kinase to abrogate the cytokine dependency of the murine lymphoid hematopoietic cell line FL5.12. Cytokine-independent cells were obtained from FL5.12 cells at a frequency of 1 x 10(-7), indicating that a low frequency of cells expressing deltaMEK1:ER were factor-independent. In general, cells that were converted to a cytokine-independent phenotype displayed a higher level of MAP kinase activity in response to deltaMEK1:ER activation than those that remained cytokine-dependent. deltaMEK1:ER-responsive cells could be maintained long-term in the presence of beta-estradiol, as well as the estrogen-receptor antagonist 4-hydroxy-tamoxifen. Removal of hormone led to the rapid cessation of cell growth in a manner similar to that observed when cytokine is withdrawn from the parental cells. GM-CSF mRNA transcripts were detected in the MEK1-responsive cells indicating that activated deltaMEK1:ER may induce a pathway leading to autocrine proliferation. Cytokine-dependent deltaMEK1:ER cells were found to increase the expression of GM-CSF receptor alpha (GM-CSFRalpha) in response to beta-estradiol. In contrast, MEK1-responsive cells were found to express constitutively lower levels of GM-CSFRalpha and beta common (betac) chains indicating that constitutive GM-CSF expression resulted in a decrease in GM-CSFR expression. Treatment of parental cells with supernatant from MEK1-responsive FL5.12 cells was sufficient to promote [3H]-thymidine incorporation. GM-CSF was found to enhance the viability of FL5.12 cells. The cell lines described here will be useful for elaborating the ability of the MAP kinase pathway to regulate cell proliferation in hematopoietic cells.
Cell Cycle↗
Enhanced ability of daniplestim and myelopoietin-1 to suppress apoptosis in human hematopoietic cells.
Modified and chimeric cytokines have been developed to aid in the recovery of hematopoietic precursor cells after myeloablative chemotherapy. The interleukin-3 (IL-3) receptor agonist, daniplestim, binds to the IL-3 receptor-alpha subunit with 60-fold greater affinity and induces cell proliferation and colony-forming unit formation 10- to 22-fold better than native IL-3. A chimeric cytokine, myelopoietin-1, composed of daniplestim and a G-CSF receptor agonist binds both the IL-3 and G-CSF receptors. While the in vivo effects of daniplestim and myelopoietin-1 are well described, the mechanisms by which they stimulate growth are not well understood. We have investigated the effects of daniplestim and myelopoietin-1 on the prevention of apoptosis in two human hematopoietic cell lines, OCI-AML.5 and AML 193. Daniplestim and myelopoietin-1 prevented apoptosis to a greater degree than native recombinant IL-3 or G-CSF as determined by annexin V/propidium iodide binding and TUNEL assays. Daniplestim and myelopoietin-1 promoted the maintenance of the mitochondrial membrane potential better than native IL-3 or G-CSF. These cytokines promoted a lower redox potential as higher levels of free radicals were detected after cytokine treatment than in cytokine-deprived cells implying increased respiration. These results indicate that daniplestim and myelopoietin-1 are able to prevent apoptosis in hematopoietic cells more effectively than native IL-3 and G-CSF. These effects of daniplestim and myelopoietin-1 may contribute to their effective ability to repopulate hematopoietic precursor cells after chemotherapy.
Apoptosis↗
Inhibition of cytokine production and interference in IL-2 receptor-mediated Jak-Stat signaling by the hydroxylamine metabolite of sulfamethoxazole.
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Cytokines↗
Focal pulmonary uptake during Tc-99m myocardial perfusion SPECT imaging.
PURPOSE: To evaluate the incidence and origin of abnormal focal pulmonary uptake during myocardial perfusion SPECT imaging (MSPECT). METHODS: For evaluation of chest pain, 790 men and 581 women (mean age, 56 +/- 13 years) underwent MSPECT. All of them received adenosine for pharmacologic stress and Tc-99m tetrofosmin (TF, n = 817) or Tc-99m sestamibi (MIBI, n = 554) for myocardial perfusion imaging. RESULTS: Review of chest radiography with or without computed tomography revealed 111 (8.1%) focal pulmonary diseases. Among them, 38 (34.2%) showed focal pulmonary uptake (TF, 22; MIBI, 16); 27 (30.7%) of 88 showed previous pulmonary tuberculosis; 2 of 10 (20%) benign pulmonary nodules; 4 of 5 (80%) metastatic lung cancers; 2 of 4 (50%) primary lung cancers; and 3 of 4 (75%) pneumonias. No difference in uptake was noted for the two imaging agents. Intensity of uptake did not vary with origin of the uptake. Focal abnormal pulmonary uptake was found in 2.8% of patients undergoing MSPECT and in 34.2% of patients in whom radiological examinations showed regional pulmonary disease. In patients with abnormal pulmonary uptake on MSPECT, 16% had a malignant lesion, whereas 75% of patients with a pulmonary nodule shown on radiography and focal pulmonary uptake on MSPECT had a malignant lesion. CONCLUSIONS: Although the incidence of abnormal pulmonary uptake during MSPECT was very low, the incidence of malignant lesions in the patients with nodular pulmonary uptake was relatively high.
Adenosine↗
Recurrent pyogenic cholangitis: comparison between MR cholangiography and direct cholangiography.
PURPOSE: To compare the accuracy of magnetic resonance (MR) cholangiography with that of direct cholangiography for the evaluation of recurrent pyogenic cholangitis. MATERIALS AND METHODS: Twenty-four patients with recurrent pyogenic cholangitis underwent MR cholangiography before surgery, and 18 of these 24 also underwent direct cholangiography. Two reviewers evaluated MR cholangiograms and direct cholangiograms and focused on identifying intrahepatic ductal dilatation, stricture, and calculi, as well as coexistent parenchymal abnormalities, on the basis of the classification of the internal lobes and segments of the liver. These observations were compared with surgical findings. RESULTS: According to examination results in the surgical specimens, 24 patients had 46 segmental abnormalities. MR cholangiography depicted all 46 (100%) segments with ductal dilatation, 22 (96%) of 23 segments with focal ductal stricture, and 43 (98%) of 44 segments with ductal calculi. Eighteen patients who underwent direct cholangiography had 32 segmental abnormalities according to examination results in the surgical specimens. Direct cholangiography depicted 15 (47%) of 32 segments with ductal dilatation, eight (44%) of 18 segments with focal ductal stricture, and 14 (45%) of 31 segments with ductal calculi. CONCLUSION: MR cholangiography is superior to direct cholangiography for accurate topographic evaluation of recurrent pyogenic cholangitis because it is able to depict all of the biliary tree, despite obstruction or stenosis.
Aged↗
An ischemic skin lesion after chemoembolization of the right internal mammary artery in a patient with hepatocellular carcinoma.
A huge nodular hepatocellular carcinoma located at the anterior superior portion of the left lobe in a patient with hepatocellular carcinoma was treated with transcatheter arterial chemoembolization through the left hepatic artery. Three months later, however, there was a re-elevation of the serum alpha-fetoprotein level and evidence of a marginal recurrence at the left side of the previously embolized tumor was noted on the postembolization computed tomographic scan. Although the hepatic artery was intact in the second hepatic arteriography, we found that the right internal mammary artery was feeding the recurred hepatocellular carcinoma. This internal mammary artery was successfully treated with Lipiodol-transcatheter arterial chemoembolization. However, an ischemic lesion occurred in the skin of the anterior chest and abdominal wall several days after internal mammary artery embolization. We report here a very rare case of ischemic skin lesion on the anterior chest and abdominal wall following transcatheter arterial chemoembolization of the right internal mammary artery. This internal mammary artery was embolized because it had developed a collateral tumor feeding vessel following the initial chemoembolization of a hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Interactions between the PI3K and Raf signaling pathways can result in the transformation of hematopoietic cells.
The PI3K/Akt and Raf/MEK/ERK signal transduction cascades are pivotal in transmitting signals from membrane receptors to downstream targets that regulate apoptosis, gene expression, and cell growth. The abilities of activated PI3K, Akt, Raf, and MEK proteins to abrogate the cytokine dependence of three different hematopoietic cell lines were determined. Activated PI3K or Akt expression by themselves did not efficiently annul cytokine dependence. Raf and MEK could abrogate the cytokine dependence of murine FDC-PI and human TF-1 cells; however, the frequency of transformation was dependent on the particular oncogene examined, as more factor-independent cells were isolated after infection with activated retroviruses encoding A-Raf or Raf-1 than were with MEK1 or B-Raf. Cytokine-independent deltaRaf-1-infected cells formed tumors on injection into immunocompromised mice, whereas cytokine-dependent cell lines did not, demonstrating the oncogenic effects of activation of the Raf/MEK/ERK pathway. Overexpression of the antiapoptotic Bcl-2 protein synergized with activation of the Raf/MEK/ERK cascade and increased the efficiency of transformation of FDC-PI and TF-1 cells. In contrast to the results observed with FDC-P1 and TF-I cells, the activated Raf genes did not relieve the cytokine dependence of murine FL5.12 cells. The abilities of the Raf and PI3K pathways to interact and annul the cytokine dependence of FL5.12 cells were determined. The combination of Raf and either PI3K or Akt expression relieved cytokine dependence of some FL5.12 cells, and the efficiency of transformation could be enhanced further by Bcl-2 or Bcl-XL overexpression. Thus, the antiapoptotic PI3K/Akt and Bcl-2/Bcl-XL proteins can interact with the growth-promoting Raf/MEK/ERK pathway and annul the cytokine dependence of certain hematopoietic cells.
Animals↗
Disruption of imprinted X inactivation by parent-of-origin effects at Tsix.
In marsupials and in extraembryonic tissues of placental mammals, X inactivation is imprinted to occur on the paternal chromosome. Here, we find that imprinting is controlled by the antisense Xist gene, Tsix. Tsix is maternally expressed and mice carrying a Tsix deletion show normal paternal but impaired maternal transmission. Maternal inheritance occurs infrequently, with surviving progeny showing intrauterine growth retardation and reduced fertility. Transmission ratio distortion results from disrupted imprinting and postimplantation loss of mutant embryos. In contrast to effects in embryonic stem cells, deleting Tsix causes ectopic X inactivation in early male embryos and inactivation of both X chromosomes in female embryos, indicating that X chromosome counting cannot override Tsix imprinting. These results highlight differences between imprinted and random X inactivation but show that Tsix regulates both. We propose that an imprinting center lies within Tsix.
Animals↗
Local radiotherapy for unresectable hepatocellular carcinoma patients who failed with transcatheter arterial chemoembolization.
PURPOSE: The purpose of this study was to investigate the efficacy of local radiotherapy (RT) as a salvage treatment for unresectable hepatocellular carcinoma (HCC) patients who failed with transcatheter arterial chemoembolization (TACE). METHODS AND MATERIALS: Patients with unresectable HCC who had been treated with and eventually failed with TACE were eligible. The judgment of TACE failure was based on incomplete tumor filling of lipiodol-adriamycin mixture on either angiography or computed tomography (CT) scan. From January 1993 to December 1997, 27 patients were entered into this study. They had UICC Stage III (17) or IVA (10) disease, with a mean tumor size of 7.2 +/- 2.9 cm. Local RT was done, with a mean tumor dose of 51.8 +/- 7.9 Gy, in daily 1.8-Gy fractions using a 10- or 6-MV linear accelerator. Survival was calculated from both the diagnosis and the start of RT using the Kaplan-Meier method. RESULTS: An objective response was observed in 16 of 24 patients (66.7%) including 1 CR. Intrahepatic metastasis was noted outside the RT field in 10 patients (37.0%). Extrahepatic distant metastasis occurred in 4 patients. Survival rates at 1, 2, and 3 years were 85. 2%, 58.1%, and 33.2%, respectively, from the diagnosis and 55.9%, 35. 7%, and 21.4%, respectively, from the start of RT. The median survivals were 26 months from the diagnosis and 14 months from the start of RT. Acute toxicity involved alteration in liver function test (13 patients) and thrombocytopenia (2 patients). Subacute and chronic toxicity involved gastroduodenal ulcer (3 patients) and duodenitis (2 patients). There was no treatment-related death. CONCLUSION: In unresectable HCC patients who failed with TACE, local RT induced a substantial tumor response of 66.7%, with a 3-year survival rate of 21.4% and a median survival time of 14 months. Toxicity was significant but manageable. Although we do not know if there is survival benefit through this treatment, local RT in these patients seems to be valuable as a salvage for TACE-failed HCC.
Adult↗
Object and spatial alternation tasks with minimal delays activate the right anterior hippocampus proper in humans.
Substantial evidence indicates that the hippocampus plays a critical role in long-term declarative memory. In contrast, the role of the human hippocampus in working memory, particularly when information needs to be maintained only for a few seconds, remains controversial. Using PET, we show robust activation of the right anterior hippocampus proper during the performance of both object and spatial alternation tasks. Hippocampal activation emerged even though subjects only had to remember a single, simple stimulus over a minimum delay of 1 s. No hippocampal activation occurred when the delay was increased to 5 s. This suggests that the role of the hippocampus in working memory is not to maintain information across a delay interval. Instead, its activity reflects a more transient function during encoding and/or retrieval. These data are among the first observations to demonstrate human hippocampal involvement in working memory.
Adult↗
Genetic engineering of drought resistant potato plants by introduction of the trehalose-6-phosphate synthase (TPS1) gene from Saccharomyces cerevisiae.
In yeast, trehalose-6-phosphate synthase is a key enzyme for trehalose biosynthesis, encoded by the structural gene TPS1. Trehalose affects sugar metabolism as well as osmoprotection against several environmental stresses, such as heat and desiccation. The TPS1 gene of Saccharomyces cerevisiae was engineered under the control of the CaMV 35S promoter for constitutive expression in transgenic potato plants by Ti-plasmid of Agrobacterium-mediated transformation. The resulting TPS1 transgenic potato plants exhibited various morphological phenotypes in culture tubes, ranging from normal to severely retarded growth, including dwarfish growth, yellowish lancet-shaped leaves, and aberrant root development. However, the plants recovered from these negative growth effects when grown in a soil mixture. The TPS1 transgenic potato plants showed significantly increased drought resistance. These results suggest that the production of trehalose not only affects plant development but also improves drought tolerance.
Agrobacterium tumefaciens↗