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Biomedical subjects

E K Lee

Publications and source records attributed to E K Lee.

At least 19 recordsLinked to original sources
PubMed1999

Actinomycin D as a novel SH2 domain ligand inhibits Shc/Grb2 interaction in B104-1-1 (neu*-transformed NIH3T3) and SAA (hEGFR-overexpressed NIH3T3) cells.

Actinomycins, a family of bicyclic chromopeptide lactones with strong antineoplastic activity, were screened as inhibitors of Shc/Grb2 interaction in in vitro assay systems. To investigate the effects of actinomycin D on Shc/Grb2 interaction in cell-based experiments, we used SAA (normal hEGFR-overexpressed NIH3T3) cells and B104-1-1 (neu*-transformed NIH3T3) cells, because a large number of the Shc/Grb2 complexes were detected. Associated protein complexes containing Shc were immunoprecipitated from actinomycin D-treated cell lysates with polyclonal anti-Shc antibody. Then the association with Grb2 was assessed by immunoblotting with monoclonal anti-Grb2 antibody. The result of the immunoblotting experiment revealed that actinomycin D inhibited Shc/Grb2 interaction in a dose-dependent manner in both B104-1-1 and EGF-stimulated SAA cells. The inhibition of Shc/Grb2 interaction by actinomycin D in B104-1-1 cells also reduced tyrosine phosphorylation of MAP kinase (Erk1/Erk2), one of the major components in the Ras-MAP kinase signaling pathway. These results suggest that actinomycin D could be a non-phosphorylated natural and cellular membrane-permeable SH2 domain antagonist.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Effects of stress on leukocyte trafficking and immune responses: implications for vaccination.

Increased susceptibility of animals to infectious disease during the periparturient period results in suffering and economic losses. Stress appears to delay inflammation by reducing efficiency of CD62L-mediated immune surveillance by phagocytes. It is important to note that the effects of stress are not limited to alteration of leukocyte trafficking patterns since various stressors (e.g., transport, parturition, and castration) also decrease IFN-gamma secretion by lymphocytes, and may decrease antigen presentation efficiency by down-regulating class II molecule expression on antigen presenting cells, and delay or impair immune responses to vaccination. Documented immunosuppression in periparturient animals, particularly the bias toward Th2 immune responses, and also changes in general leukocyte trafficking patterns suggest that vaccination intending to elicit cell-mediated immunity may not be efficacious at this point of the production cycle. Based on findings of numerous periparturient studies on immunosuppression in cattle, waiting at least 30 days after parturition before administering routine vaccinations is recommended.

Animals↗
PubMed1999

Conditional expression and signaling of a specifically designed Gi-coupled receptor in transgenic mice.

To control G protein signaling in vivo, we have modified G protein-coupled receptors to respond exclusively to synthetic small molecule agonists and not to their natural agonist(s). These engineered receptors are designated RASSLs (receptor activated solely by a synthetic ligand). A prototype RASSL (Ro1) based on the Gi-coupled K opioid receptor was expressed in transgenic mice under the control of the tetracycline transactivator (tet) system. Activation of Ro1 expressed in the heart decreased heart rate by up to 80%, an expected effect of increased Gi signaling. Maximal heart rate changes occurred in less than 1 min, demonstrating the speed of this inducible signaling system. This Ro1-mediated slowing of heart rate was also subject to desensitization, which lasted more than 24 h. Both the initial effect on heart rate and the desensitization occurred, even though Ro1 is derived from a human opioid receptor not normally involved in heart rate control. In addition, the tet system was used to induce Ro1 expression in hepatocytes and salivary gland, where Gi signaling is known to control physiologic events such as proliferation and secretion. These studies demonstrate that a RASSL can be inducibly expressed in several mouse tissues and used in vivo to activate G protein signaling in a controllable fashion.

Animals↗
PubMed1999

Treatment planning for brachytherapy: an integer programming model, two computational approaches and experiments with permanent prostate implant planning.

An integer linear programming model is proposed as a framework for optimizing seed placement and dose distribution in brachytherapy treatment planning. The basic model involves using 0/1 indicator variables to describe the placement or non-placement of seeds in a prespecified three-dimensional grid of potential locations. The dose delivered to each point in a discretized representation of the diseased organ and neighbouring healthy tissue can then be modelled as a linear combination of the indicator variables. A system of linear constraints is imposed to attempt to keep the dose level at each point to within specified target bounds. Since it is physically impossible to satisfy all constraints simultaneously, each constraint uses a variable to either record when the target dose level is achieved, or to record the deviation from the desired level. These additional variables are embedded into an objective function to be optimized. Variations on this model are discussed and two computational approaches--a branch-and-bound algorithm and a genetic algorithm--for finding 'optimal' seed placements are described. Results of computational experiments on a collection of prostate cancer cases are reported. The results indicate that both optimization algorithms are capable of producing good solutions within 5 to 15 min, and that small variations in model parameters can have a measurable effect on the dose distribution of the resulting plans.

Algorithms↗
PubMed1999

A case of edematous striae distensae in lupus nephritis.

A 17-year-old girl with systemic lupus erythematosus presented with painful edematous abdominal striae. She had been treated with systemic steroid for the systemic lupus erythematosus. At the time of presentation, she had abruptly gained 10 kg due to combined lupus nephritis. The histopathologic finding of the edematous striae distensae included dermal edema with separation of collagen fibers and small fragmented elastic fibers. Edematous striae distensae are uncommon but can develop from the combined effects of glucocorticoid and generalized edema.

Abdomen↗
PubMed1998

Cloning and sequencing of cDNA encoding bovine tumor necrosis factor (TNF)-receptor I.

Tumor necrosis factor (TNF) is a multipotent cytokine produced by activated macrophages and lymphocytes and its activity is mediated by specific cell surface receptors, TNF-RI and TNF-RII. We have isolated and analyzed a cDNA encoding bovine TNF-RI gene and compared it with known TNF-RI sequences from other species. The cDNA sequence for the coding region of bovine TNF-RI shows 80% homology with porcine TNF-RI and 77% with human TNF-RI. The cDNA sequence of bovine TNF-RI codes for 471 amino acids and shows 75% and 67% identity with the amino acid sequences of porcine TNF-RI and human TNF-RI, respectively. The predicted bovine TNF-RI amino acid sequence consists of a signal peptide, an extracellular domain, a transmembrane region and a cytoplasmic tail. The extracellular region contains four repeated cysteine rich domains, which are conserved in all species. Northern blot results show that bovine TNF-RI gene is expressed in neutrophils and mononuclear leukocytes.

Amino Acid Sequence↗
PubMed1998

Somatostatin inhibits (d-Arg6, Pro9-NEt) salmon gonadotropin-releasing hormone- and dopamine D1-stimulated growth hormone release from perifused pituitary cells of chinese grass carp, ctenopharyngodon idellus.

In this study, a heterologous radioimmunoassay (RIA) for grass carp GH has been validated and used to monitor the kinetics of GH release from perifused grass carp pituitary cells. To establish the anatomical specificity of GH antiserum used in this RIA, immunohistochemical staining was performed in grass carp pituitary sections. Somatotrophs recognized by this GH antiserum were located mainly in the proximal pars distalis without overlapping with gonadotrophs located in the same area or with lactotrophs located in the rostral pars distalis. The immunoreactivity of somatotrophs was abolished by preabsorbing GH antiserum with purified grass carp GH, suggesting that the possibility of a cross-reactivity of antiserum with other grass carp pituitary hormones is unlikely. Using 125I-labeled carp GH as the RIA tracer, parallelism was observed among the displacement curves of grass carp GH standard, grass carp serum, and culture medium conditioned by grass carp pituitary cells, suggesting that this RIA can be used to quantitate grass carp GH levels in biological samples. Using an in vitro column perifusion system, a superactive gonadotropin-releasing hormone (GnRH) analog (d-Arg6, Pro9-NEt)-sGnRH(sGnRHa, 0.3-30 nM), dopamine (DA, 0.1-10 muM), and the nonselective DA agonist apomorphine (0.1-10 muM) stimulated GH release from grass carp pituitary cells in a dose-dependent manner. The GH-releasing effect of DA was mimicked by the D1 agonists SKF38393 (0.1-10 muM) and SKF77434 (0.1-10 muM), but not by the D2 agonist LY171555 (3 muM). In addition, the GH response to DA (1 muM) was blocked by the D1 antagonist SCH23390 (5 muM) but not by the D2 antagonist (+/-) sulpiride (5 muM), suggesting that the GH-releasing action of DA is mediated through receptors resembling mammalian D1 receptors. Somatostatin-14 (SRIF14, 0.01-100 nM), unlike sGnRHa and DA, induced a dose-dependent suppression on basal GH release. At a high dose (100 nM), SRIF14 also abolished the GH responses to sGnRHa (100 nM), DA (10 muM), and the D1 agonist SKF38393 (3 muM). These results, as a whole, provide evidence that GH release in the grass carp is under the direct regulation of GnRH, DA, and SRIF at the pituitary cell level. The present study also suggests that DA D1 receptors are present in grass carp pituitary cells mediating the GH-releasing action of DA.

Animals↗
PubMed1998

Generators of short latency human somatosensory-evoked potentials recorded over the spine and scalp.

Somatosensory evoked potentials (SEPs) are most commonly obtained after stimulation of the median nerve and the posterior tibial nerve. SEPs reflect conduction of the afferent volley along the peripheral nerve, dorsal columns, and medial lemniscal pathways to the primary somatosensory cortex. Short-latency SEPs are recorded over the spine and scalp. After posterior tibial nerve stimulation, the following waveforms are recorded: N22, W3, the dorsal column volley, N29, P31, N34, and P37. After median nerve stimulation, the brachial plexus volley, dorsal column volley (N11), N13, P14, N18, N20, and P22 potentials are recorded. We discuss the current state of knowledge about the generators of these SEPs. Such information is crucial for proper interpretation of SEP abnormalities.

Afferent Pathways↗
PubMed1998

Morvan's fibrillary chorea: a paraneoplastic manifestation of thymoma.

Morvan's fibrillary chorea is a rare disease characterised by symptoms which include neuromyotonia, cramping, weakness, pruritus, hyperhidrosis, insomnia, and delirium. The first case of Morvan's fibrillary chorea to be associated with clinical manifestations of myasthenia gravis with thymoma, psoriasis, and atopic dermatitis is reported. Muscle histopathology disclosed chronic denervation and myopathic changes and in vitro electrophysiology demonstrated both presynaptic and postsynaptic defects in neuromuscular transmission. Serum antibodies to acetylcholine receptors, titin, N-type calcium channels, and voltage gated potassium channels were detected. Plasmapheresis, thymectomy, and long term immunosuppression induced a dramatic resolution of symptoms. The association of thymoma with other autoimmune disorders and autoantibodies, and prolonged and sustained remission with chronic immunosuppression, place Morvan's fibrillary chorea on the range of neurological diseases arising as a paraneoplastic complication of cortical thymomas.

Biopsy↗
PubMed1998

Expression of adhesion molecules on neutrophils of periparturient cows and neonatal calves.

OBJECTIVE: To determine expression of the beta 2-integrin (CD18) family of adhesion molecules and L-selectin (CD62L) on neutrophils from periparturient cows and calves. ANIMALS: 8 periparturient Holstein cows and 9 Holstein calves. PROCEDURE: Constitutive CD18 and CD62L expression on neutrophils was determined by flow cytometry, using specific monoclonal antibodies. Platelet-activating factor was used to activate neutrophils in vitro to measure down-regulation of CD62L and up-regulation of CD18 on activated neutrophils. RESULTS: Mean values for constitutive and platelet-activating factor-stimulated CD18 expression on neutrophils from cows and calves were highest at parturition, then decreased during the first 24 hours after parturition on calf neutrophils, whereas CD62L expression decreased markedly by 9 to 24 hours after parturition on cow and calf neutrophils. Constitutive amounts of CD18 and CD62L on cow neutrophils returned to prepartum values by day 3 after parturition. Amounts of CD18 expression on calves' neutrophils recovered by 1 week of age, but did not reach original birth values, whereas CD62L expression exceeded birth values by day 3 after parturition. Cows had leukocytosis (neutrophilia), with a doubling of circulating neutrophils 9 hours after calving that was inversely correlated with CD62L expression on neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: Low amounts of CD62L and CD18 on calf neutrophils and of CD62L on neutrophils from cows for several days after parturition may result in impaired inflammatory response. Low CD62L expression may contribute to increased susceptibility to disease.

Animals↗
PubMed1998

The seventh nationwide tuberculosis prevalence survey in Korea, 1995.

SETTING: Nationwide random sample survey for tuberculosis prevalence in Korea in 1995. OBJECTIVE: To investigate the prevalence of tuberculosis infection, morbidity and drug resistance, and BCG coverage, and to compare the findings with those of the previous six surveys. DESIGN: The following investigations were performed: tuberculin test, BCG scar screening, chest miniature radiography (70 x 70 mm) for those aged over five years, sputum direct smear, culture and drug susceptibility test, and a questionnaire to obtain history of antituberculosis chemotherapy and symptoms. RESULTS: The coverages of the 1995 survey were as follows: tuberculin 87.0%, radiology 88.4%, bacteriology 98.3%. The observed tuberculin positivity (> or =10 mm in diameter) of subjects aged under 30 was 15.5%. The prevalence of pulmonary tuberculosis per 100000 has decreased in the last 30 years: direct smear positive from 686 to 93, smear and/or culture positive from 940 to 219, active tuberculosis from 5065 to 1032. Rates of drug resistance have also fallen: of those with no previous chemotherapy from 26.2% to 5.8%, of those with history of chemotherapy from 55.2% to 25.0%, and in total from 38.0% to 9.9%. BCG scar prevalence of infants (aged under one year) was 87.7%, and of those under 30 it was 91.8% in 1995. CONCLUSION: Tuberculosis prevalences and the drug resistance rates have decreased significantly.

Adolescent↗
PubMed1998

Cohort analyses of the treatment of smear-positive pulmonary tuberculosis patients under programme conditions in Korea, 1983-1994.

SETTING: Cohort analyses of the results of sputum smear-positive pulmonary tuberculosis patients registered in health centres in Korea under programme conditions from 1983 to 1994. OBJECTIVE: To assess the overall treatment results and their annual changing trend. DESIGN: Retrospective sample surveys of the nationwide treatment results of registered new smear-positive and retreatment patients. RESULTS: The numbers of registered smear-positive pulmonary tuberculosis patients have decreased steadily, from over 35000 in 1983 to about 14000 in 1994. Over 90% of health centres, and 60-80% of registered patients, were covered in the cohort analyses. The overall cure rate for all patients was 56% in 1983; this improved to around 80% in the last three years of the period studied, owing to increased use of short-course chemotherapy. Over 5000 patients per year required retreatment during the first four years; this number decreased steadily to less than 700 in 1994, due to the reduction in initial treatment failures. CONCLUSION: The overall treatment results have improved significantly in Korea, due to the application of short-course chemotherapy.

Antitubercular Agents↗
PubMed1998

Tuberculin PPD RT23: has it lost some of its potency?

PPD RT23 is a tuberculin that is used worldwide. Korea has been using 1TU RT23 for its nationwide tuberculosis prevalence surveys at five-yearly intervals since 1965, and found a drop in its potency after the 1975 survey. This finding draws attention to the interpretation of tuberculin survey data observed with RT23 at different time periods.

Adolescent↗
PubMed1997

Molecular cloning of leukotactin-1: a novel human beta-chemokine, a chemoattractant for neutrophils, monocytes, and lymphocytes, and a potent agonist at CC chemokine receptors 1 and 3.

A new member of human beta-chemokine cDNA was isolated and named leukotactin-1 (Lkn-1). Lkn-1, along with murine macrophage inflammatory protein-related protein-1 and -2, defines a subgroup of beta-chemokines based on two conserved cysteines in addition to the four others conserved in all beta-chemokines. The putative mature Lkn-1 is composed of 92 amino acids with a calculated m.w. of 10,162. The Lkn-1 gene was mapped to human chromosome 17, region q12. Recombinant Lkn-1 was a potent chemoattractant for neutrophils, monocytes, and lymphocytes and induced calcium flux in these cells. Lkn-1 specifically induced calcium flux in CCR1- and CCR3-expressing HOS cell lines. Lkn-1 suppressed colony formation by human granulocyte-macrophage, erythroid, and multipotential progenitor cells stimulated by combinations of growth factors. Hence, we have isolated and characterized a human C6 beta-chemokine that is a potent agonist at CCR1 and CCR3 and shows broad biologic activities, including leukocyte chemoattraction.

Amino Acid Sequence↗