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T B Lee

Publications and source records attributed to T B Lee.

At least 19 recordsLinked to original sources
PubMed2001

Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100.

A major obstacle to successful cancer chemotherapy is the development of multidrug resistance (MDR). The previous study revealed that a doxorubicin-resistant AML subline (AML-2/DX100) overexpressed an MDR-associated protein (MRP) but not P-glycoprotein. The AML-2/DX100 also showed various levels of resistance to daunorubicin and vincristine but was paradoxically sensitive to hydrogen peroxide (5-fold), t-butyl hydroperoxide (3-fold), and paraquat (2-fold) when compared to the drug-sensitive parental AML-2 cells (AML-2/WT). We compared the activities of antioxidant enzymes to detoxify reactive oxygen species (ROS), including superoxide dismutases, glutathione S-transferase, catalase, glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase in both AML-2/WT and AML-2/DX100. Interestingly, of these antioxidant enzymes, catalase activity of AML-2/DX100 decreased significantly to about one-third that of AML-2/WT (P < 0.000005). The decreased activity of catalase was due to reduced expression of the catalase gene; confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The decreased activity of catalase was maintained even in the absence of doxorubicin for 3 months as well as by the treatment of probenecid, an MRP inhibitor. In addition, there was no difference in catalase activity between HL-60 and another MRP-overexpressing subline HL-60/Adr. Taken together, the paradoxical increase in the sensitivity of an MRP-overexpressing AML-2/DX100 in response to peroxides and paraquat is due to the down-regulation of catalase gene expression, which totally independent of overexpression of MRP. It is therefore possible that decreased catalase activity could be exploited as an Achilles' heel in resistant cells such as this.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Reactive oxygen species-specific mechanisms of drug resistance in paraquat-resistant acute myelogenous leukemia sublines.

Reactive oxygen species (ROS)-specific mechanisms of drug resistance were explored in paraquat (PQ)-resistant acute myelogenous leukemia cell (OCI/AML-2) sublines. For this, PQ-resistant AML sublines, AML-2/PQ100 and AML-2/PQ400, were selected in the presence of PQ concentrations of 100 microg/ml and 400 microg/ml, respectively. They showed a moderate level of cross resistance to cisplatin and doxorubicin. They were also slightly more resistant than the parental cell (AML-2/WT) to etoposide, camptothecin and daunorubicin. The resistance of PQ-resistant AML-2 sublines to cisplatin seemed to be due to increased amounts of metallothionein, which was not only supported by reversal of resistance to cisplatin by propargylglycin (an inhibitor of metallothionein synthesis) but also confirmed by Western blot analysis and reverse transcription-PCR assay. In addition, both AML-PQ100 and /PQ400 sublines showed increased activities of Cu-, Zn-containing superoxide dismutase (Cu,Zn-SOD) and Mn-containing superoxide dismutase (Mn-SOD), whereas AML-2/PQ400, but not AML-2/PQ100, showed increased glutathione S-transferase activity as compared to that of AML-2/WT. However, there was no difference in other ROS-related cellular antioxidants between AML-2/WT and its PQ-resistant sublines. Taken together, these results strongly suggest that increases in levels of metallothionein, glutathione S-transferase, Cu,Zn-SOD and Mn-SOD play important roles in protective mechanisms against toxicity of PQ or ROS in AML cells.

Alkynes↗
PubMed1998

Recommended practices for surveillance. Association for Professionals in Infection Control and Epidemiology, Inc. Surveillance Initiative working Group.

Demonstration of quality health care includes documentation of outcomes of care. Surveillance is a comprehensive method of measuring outcomes and related processes of care, analyzing the data, and providing information to members of the health care team to assist in improving those outcomes. Surveillance is an essential component of effective clinical programs designed to reduce the frequency of adverse events such as infection or injury. Although there is no single or "right" method of surveillance design or implementation, sound epidemiologic principles must form the foundation of effective systems and must be understood by key participants in the surveillance program and supported by senior management. Teamwork and collaboration across the health care spectrum are important for the development of surveillance plans. Each health care organization must tailor its surveillance systems to maximize resources by focusing on population characteristics, outcome priorities, and organizational objectives. To ensure quality of surveillance, the following elements must be incorporated: A written plan should serve as the foundation of any surveillance program. The plan should outline important objectives and elements of the surveillance process so that resources can be targeted appropriately. Thoroughness or intensity of surveillance for an area of interest must be maintained at the same level over time. Fluctuations of a surveillance rate have no meaning unless the same level of data collection is maintained. External rate comparisons are meaningless unless the systems used have comparable intensity. All the elements of surveillance should be used with consistency over time. This includes application of surveillance definitions and rate calculation methods. Personnel resources need to be appropriate for the type of surveillance being performed. This includes trained professionals who understand epidemiology and who have access to continuing professional education opportunities. Other resources essential to surveillance include computer support, information and technology services, clerical services, and administrative understanding and support to maintain a quality program. As a means of quality control and to ensure accuracy, the data and process of surveillance should undergo periodic evaluation and validation. This document is intended to assist professionals who plan and conduct surveillance programs as well as those who assure that there is appropriate organizational support to accomplish appropriate surveillance. While design of surveillance systems must be unique for each organization, incorporation of these seven core Recommended Practices for Surveillance provides a scientific framework to approach surveillance programs.

Cross Infection↗
PubMed1997

Surveillance in acute care and nonacute care settings: current issues and concepts.

Infection surveillance programs should be designed to meet the needs of a given health care organization. Opportunities to learn how to design epidemiologically sound surveillance programs are not readily available. This report describes the results of small-group discussions held with infection control professionals from various health care settings. Facilitators coached participants through a series of discussions to generate ideas about scientific surveillance for specific patient populations. Key strategies were identified, and suggestions for surveillance studies were given. Before these strategies can be widely recommended, reports of actual application are needed.

Health Facilities↗
PubMed1994

Synthesis, resolution, and SAR of (+/-)-2-amino-N-methyl-alpha-(3-methyl-2-thienyl)benzeneethanamine++ + and related analogs as noncompetitive NMDA antagonists with neuroprotective properties.

The preparation and structure-activity relationships of a series of 2-amino-alpha-thienylbenzeneethanamines are described. From this work, (+/-)-2-amino-N-methyl-alpha-(3-methyl-2-thienyl)-benzeneethanamine++ + (3a) and the homologous N-ethyl analog 3b emerged as novel noncompetitive NMDA antagonists with neuroprotective properties. Optical resolution of 3a and X-ray crystallography of (+)3a were performed. The racemate and enantiomers were evaluated for neuroprotective properties in models of ischemia-induced hippocampal damage (gerbil) and cerebral focal ischemia (rat). Pretreatment with 3a, (+)3a, or (-)3a significantly reduced ischemia-induced CA1 hippocampal damage. Posttreatment with 3a afforded a lower degree of neuroprotection. A highly significant reduction in infarct volume was observed with 3a in the cerebral focal ischemia model, with only weak positive effects being displayed by (+)3a. Dose-limiting side effects were associated with all three compounds in this model. In summary, the results demonstrate the utility of noncompetitive NMDA antagonists as neuroprotective agents for ischemia-induced neurodegeneration.

Aniline Compounds↗
PubMed1986

Effect of nedocromil sodium on the immediate response to antigen challenge in asthmatic patients.

In this double-blind placebo controlled crossover study the protective effect of nedocromil sodium against bronchial allergen challenge was evaluated in ten asthmatic patients. Single doses of 0.5, 1.0 and 2.0 mg nedocromil sodium, administered as a pressurized aerosol 3 hr prior to challenge, were each significantly more effective than placebo in inhibiting allergen-induced bronchoconstriction. The 1.0 and 2.0 mg doses of the active drug were significantly more effective than the 0.5 mg dose. No significant difference was demonstrated between the 1.0 and 2.0 mg doses. Duration of protection beyond 3 hr was not tested. The results suggest that nedocromil sodium may be a potentially useful therapeutic agent and is worthy of further evaluation for the treatment of reversible obstructive airways disease.

Adolescent↗
PubMed1977

New orally effective chromosome derivatives for the treatment of asthma.

Two new chromone derivatives have been identified which possess oral anti-allergic activity in the rat PCA model of immediate hypersensitivity. They may have a wider spectrum of anti-allergic activity than disodium cromoglycate (SCG) since they are effective in in vitro tests involving sensitized basophils, in which SCG is inactive. Both compounds, when given orally, provide relief from experimental and clinical asthma in man.

Animals↗
PubMed1977

Antagonists of slow reacting substance of anaphylaxis. Synthesis of a series of chromone-2-carboxylic acids.

A series of substituted chromone-2-carboxylic acids was synthesized and tested as antagonists of SRS-A induced contractions of isolated guinea pig ileum. This work led to the discovery of sodium 7-[3-(4-acetyl-3hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (FPL 55712) which is the first reported specific antagonist of SRS-A. Some structural requirements for biological activity within this series are discussed.

Animals↗
PubMed1977

Further studies on the SRS-A antagonist FPL 55712.

FPL 55712, previously reported to be a selective antagonist of SRS-A on the guinea-pig ileum, has now been shown to be similarly selective, though less potent, in its antagonism of contractions induced by SRS-A on in vitro preparations of respiratory smooth muscle (human bronchial strips and guinea-pig tracheal tubes). In vivo, bronchoconstriction induced in guinea-pigs by the endogenous release of SRS-A was partially inhibited by relatively large intravenous doses of FPL 55712 and by inhalation of aerosol compound. FPL 55712 was very rapidly cleared following intravenous administration.

Animals↗
PubMed1976

Neonatal meningitis and mastoiditis caused by Hemophilus influenzae.

A newborn infant developed Hemophilus influenzae meningitis associated with acute coalescent mastoiditis and a cutaneous abscess in the mastoid region. Mastoidectomy was followed by prompt recovery from the meningitis, which had failed to clear previously despite antibiotic therapy. Mastoiditis may exist as an infective focus in neonatal meningitis more frequently than has been appreciated. Mastoid roentgenograms are usually the only clue to diagnosis of this infection and should be obtained in patients with neonatal meningitis responding poorly to antibiotic therapy.

Acute Disease↗
PubMed1976

Benzodipyran derivatives with antiallergic activity.

The synthesis and antiallergic activity of a number of benzodipyrandicarboxylic acids are described. Antiallergic activity of the compounds was determined using the homologous passive cutaneous anaphylaxis (PCA) reaction in the rat. The structural requirements for activity in the PCA screen are discussed. In this test system the linear benzodipyrans are more active than their angular analogues.

Animals↗