Biomedical subjects

F S Lee

Publications and source records attributed to F S Lee.

At least 19 recordsLinked to original sources

PubMed2003

Limit on the electron neutrino magnetic moment from the kuo-sheng reactor neutrino experiment.

A search of neutrino magnetic moment was carried out at the Kuo-Sheng Nuclear Power Station at a distance of 28 m from the 2.9 GW reactor core. With a high purity germanium detector of mass 1.06 kg surrounded by scintillating NaI(Tl) and CsI(Tl) crystals as anti-Compton detectors, a detection threshold of 5 keV and a background level of 1 kg(-1) keV(-1) day(-1) at 12-60 keV were achieved. Based on 4712 and 1250 h of reactor ON and OFF data, respectively, the limit on the neutrino magnetic moment of mu(nu;(e))<1.3x10(-10)mu(B) at 90% confidence level was derived. An indirect bound of the nu;(e) radiative lifetime of m(3)(nu)tau(nu)>2.8x10(18) eV(3) s can be inferred.

Journal Article↗

PubMed2001

HIF-1alpha binding to VHL is regulated by stimulus-sensitive proline hydroxylation.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a global transcriptional regulator of the hypoxic response. Under normoxic conditions, HIF-1alpha is recognized by the von Hippel-Lindau tumor-suppressor protein (VHL), a component of an E3 ubiquitin ligase complex. This interaction thereby promotes the rapid degradation of HIF-1alpha. Under hypoxic conditions, HIF-1alpha is stabilized. We have previously shown that VHL binds in a hypoxia-sensitive manner to a 27-aa segment of HIF-1alpha, and that this regulation depends on a posttranslational modification of HIF-1alpha. Through a combination of in vivo coimmunoprecipitation assays using VHL and a panel of point mutants of HIF-1alpha in this region, as well as MS and in vitro binding assays, we now provide evidence that this modification, which occurs under normoxic conditions, is hydroxylation of Pro-564 of HIF-1alpha. The data furthermore show that this proline hydroxylation is the primary regulator of VHL binding.

Amino Acid Sequence↗

PubMed2001

I kappa B kinase is critical for TNF-alpha-induced VCAM1 gene expression in renal tubular epithelial cells.

The expression of VCAM1 is up-regulated in renal proximal tubular epithelial cells (TEC) in a variety of inflammatory renal diseases, a prominent example of which is acute renal allograft rejection. VCAM1 may play an important role in these diseases because it binds to the integrins very late Ag-4 and alpha(4)beta(7) on lymphocytes and monocytes, thereby providing a potential mechanism to recruit these leukocytes to sites of inflammation. The molecular mechanisms underlying VCAM1 regulation in renal TEC are essentially unknown. We now report that VCAM1 mRNA is dramatically up-regulated in C1, a cell line derived from renal TEC, on exposure to TNF-alpha. Two NF-kappaB binding sites in the VCAM1 promoter are critical for the TNF-alpha-induced VCAM1 transcriptional up-regulation, and both sites bind to p65-p50 NF-kappaB complexes. TNF-alpha induces activation of inhibitor of NF-kappaB (IkappaB) kinase-beta (IKK-beta), a protein kinase that phosphorylates the NF-kappaB inhibitor IkappaB, and thereby targets the latter for degradation via the ubiquitin-proteasome pathway. Moreover, dominant negative versions of IKK inhibit TNF-alpha activation of a VCAM1 promoter reporter. We conclude that the IKK/NF-kappaB pathway is critical in the TNF-alpha-induced up-regulation of VCAM1 mRNA in renal TEC.

Animals↗

PubMed2001

Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein.

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that plays a critical role in regulating genes involved in erythropoiesis and angiogenesis. Recent evidence indicates that the von Hippel-Lindau tumor suppressor protein (VHL) is part of a ubiquitin ligase complex that promotes the degradation of HIF-1alpha under normoxic conditions. Under hypoxic conditions, HIF-1alpha is markedly stabilized. A critical issue in understanding the hypoxic response is the identification of hypoxia-regulated steps. We show here that hypoxia and cobalt treatment modulate the capacity of a HIF-1alpha fragment comprising residues 531-652 to coimmunoprecipitate with VHL. Hypoxia and cobalt both significantly diminish the interaction, and furthermore, normoxia treatment after hypoxia rapidly normalizes it. This HIF-1alpha fragment confers hypoxia and cobalt inducibility on a heterologous protein. Significantly, contained within this fragment is a short 27-residue sequence that behaves identically in all respects noted above. Finally, evidence is provided to show that cobalt and hypoxia both induce a posttranslational modification (or loss of one) in HIF-1alpha that affects its binding to VHL. We propose that dynamic, site-specific interaction of HIF-1alpha with VHL provides one mechanism by which HIF-1alpha can be regulated.

Amino Acid Sequence↗

PubMed2001

Activation of Trk neurotrophin receptors in the absence of neurotrophins.

Neurotrophins regulate neuronal cell survival and synaptic plasticity through activation of Trk receptor tyrosine kinases. Binding of neurotrophins to Trk receptors results in receptor autophosphorylation and downstream phosphorylation cascades. Here, we describe an approach to use small molecule agonists to transactivate Trk neurotrophin receptors. Activation of TrkA receptors in PC12 cells and TrkB in hippocampal neurons was observed after treatment with adenosine, a neuromodulator that acts through G protein-coupled receptors. These effects were reproduced by using the adenosine agonist CGS 21680 and were counteracted with the antagonist ZM 241385, indicating that this transactivation event by adenosine involves adenosine 2A receptors. The increase in Trk activity could be inhibited by the use of the Src family-specific inhibitor, PP1, or K252a, an inhibitor of Trk receptors. In contrast to other G protein-coupled receptor transactivation events, adenosine used Trk receptor signaling with a longer time course. Moreover, adenosine activated phosphatidylinositol 3-kinase/Akt through a Trk-dependent mechanism that resulted in increased cell survival after nerve growth factor or brain-derived neurotrophic factor withdrawal. Therefore, adenosine acting through the A(2A) receptors exerts a trophic effect through the engagement of Trk receptors. These results provide an explanation for neuroprotective actions of adenosine through a unique signaling mechanism and raise the possibility that small molecules may be used to elicit neurotrophic effects for the treatment of neurodegenerative diseases.

Adenosine↗

PubMed2001

Association of Trk neurotrophin receptors with components of the cytoplasmic dynein motor.

Nerve growth factor (NGF) initiates its trophic effects by long-range signaling through binding, internalization, and transport of a ligand-receptor complex from the axon terminal to the cell body. However, the mechanism by which retrograde transport of NGF takes place has not been elucidated. Here we describe an interaction between the Trk receptor tyrosine kinase and a 14 kDa light chain of cytoplasmic dynein. After transfection in human embryonic kidney 293 cells, this 14 kDa dynein light chain was found to bind to TrkA, TrkB, and TrkC receptors. Mapping experiments indicated that the 14 kDa dynein light chain binds to the distal region of the TrkA juxtamembrane domain. Coimmunoprecipitation experiments in vivo indicate that Trk receptors are in a complex with the 14 kDa light chain and 74 kDa intermediate chain of dynein. Confirming the physiological relevance of this association, a marked accumulation of Trk with the 14 kDa and the 74 kDa dynein components was observed after ligation of the sciatic nerve. The association of Trk receptors with components of cytoplasmic dynein suggests that transport of neurotrophins during vesicular trafficking may occur through a direct interaction of the Trk receptor with the dynein motor machinery.

Animals↗

PubMed2001

Analysis of nitrated polynuclear aromatic hydrocarbons.

A derivatization-gas chromatography/electron capture detector (GC/ECD) method has been developed for the measurement of trace nitrated polynuclear aromatic hydrocarbons (NPAHs) in air. The method involves first the derivatization of parent nitro-PAHs to their corresponding fluorinated derivatives, followed by GC/ECD analysis. The sensitivity of the method is an order of magnitude higher than those of direct GC/ECD analysis of NPAHs themselves. The method is simple and robust and thus ideally suited for the routine monitoring of NPAHs in air samples. The sensitivity and reproducibility of GC/negative ion chemical ionization MS (NICIMS) for the measurement of NPAHs after derivatization has been evaluated. The method has sensitivity comparable to GC/ECD, but is less reproducible in quantification. The method is therefore suitable for method validation and NPAHs peak confirmation rather than routine operations.

Air Pollutants↗

PubMed2001

The uniqueness of being a neurotrophin receptor.

Neurotrophins rely on Trk tyrosine kinase and p75 receptors for signal transduction. Recently, other roles for these receptors have been identified. Many questions have been raised about the mechanism by which these receptors mediate diverse cellular functions. Studies indicate a great deal of neurotrophin signaling specificity may stem from ligand-receptor selectivity and intracellular protein recruitment.

Animals↗

PubMed2000

IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection.

The generation of an adaptive immune response against intracellular pathogens requires the recruitment of effector T cells to sites of infection. Here we show that the chemokine IP-10, a specific chemoattractant for activated T cells, controls this process in mice naturally infected with Toxoplasma gondii. Neutralization of IP-10 in infected mice inhibited the massive influx of T cells into tissues and impaired antigen-specific T cell effector functions. This resulted in >1000-fold increase in tissue parasite burden and a marked increase in mortality compared to control antibody-treated mice. These observations suggest that IP-10 may play a broader role in the localization and function of effector T cells at sites of Th1 inflammation.

Animals↗

PubMed2000

Human granulocytic ehrlichiosis presenting as facial diplegia in a 42-year-old woman.

Neurologic manifestations of human ehrlichiosis are unusual and have been described almost exclusively in human monocytic ehrlichiosis associated with Ehrlichia chaffeensis. We report here a case of a previously healthy 42-year-old woman who developed bilateral facial nerve palsies in association with infection by the agent of human granulocytic ehrlichiosis (aoHGE). The diagnosis was made by specific polymerase chain reaction amplification of aoHGE sequences from samples of the patient's blood and cerebrospinal fluid (CSF), as well as propagation of aoHGE in culture of HL60 cells inoculated with the patient's CSF. To our knowledge, this is the first report directly demonstrating the presence of aoHGE in CSF, and it underscores the importance of considering HGE in patients presenting with a nonspecific febrile illness and unexplained neurologic manifestations. HGE should also be considered in the differential diagnosis of bilateral facial palsy-a rare occurrence.

Adult↗

PubMed1999

Gender-specific effects of drugs on hearing levels of older persons.

As part of a study of human presbyacusis, a questionnaire on medicinal drug usage was given to 357 subjects (184 females, 173 males). Previous results from 211 subjects showed gender effects, that is, for males, none of the drugs had any measurable effects on hearing, whereas women taking calcium channel blockers (CCBs) had hearing levels 12 dB better than women not taking them; women taking beta adrenergic medication had hearing levels 20 dB poorer, and women taking antihistamine/cold preparations had hearing levels 9 dB poorer. Results from the original 211 subjects were confirmed when the sample size was increased from 211 to 357 subjects only for the beta adrenergic medications. Results for antihistamine/cold preparation medications showed small effects only for female subjects. Data from 13 additional female subjects who used CCBs showed hearing levels 10-14 dB poorer than predicted from the original data. Male data were consistent in both samples. The inconsistency for females could reflect sampling error. A more likely possibility is that since the original 10 subjects using CCBs had a mean age of 72 yr and the second sample of 13 had a mean age of 79.5 yr, poorer hearing levels might be anticipated because of the difference in chronological age and possibly duration of drug usage.

Adrenergic beta-Agonists↗

PubMed1999

Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta.

Recent evidence indicates that nuclear factor-kappaB (NF-kappaB), a transcription factor critically important for immune and inflammatory responses, is activated by a protein kinase cascade. The essential features of this cascade are that a mitogen-activated protein kinase kinase kinase (MAP3K) activates an IkappaB kinase (IKK) that site-specifically phosphorylates IkappaB. The IkappaB protein, which ordinarily sequesters NF-kappaB in the cytoplasm, is subsequently degraded by the ubiquitin-proteasome pathway, thereby allowing the nuclear translocation of NF-kappaB. Thus far, only two MAP3Ks, NIK and MEKK1, have been identified that can activate this pathway. We now show that MEKK2 and MEKK3 can in vivo activate IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and, relatively modestly, activate an NF-kappaB reporter gene. In addition, dominant negative versions of either IKK-alpha or IKK-beta abolish NF-kappaB activation induced by MEKK2 or MEKK3, thereby providing evidence that these IKKs mediate the NF-kappaB-inducing activities of these MEKKs. In contrast, other MAP3Ks, including MEKK4, ASK1, and MLK3, fail to show evidence of activation of the NF-kappaB pathway. We conclude that a distinct subset of MAP3Ks can activate NF-kappaB.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1999

[Estimation of the octanol-water partition coefficients of PAHs by solid-phase microextraction].

Eleven PAHs were analyzed by solid-phase microextraction-gas chromatography/ion trap detector and their partition coefficients were obtained at equilibrium. When the polymer coating of the fiber may be viewed as one kind of organic solvent, the linear free energy relationship between the polydimethylsiloxane-water partition coefficient (Ksw) and octanol-water partition coefficient (Kow) was established by solid-phase microextraction, which was log Ksw = 0.9318 log Kow-0.2056 with good correlation coefficient 0.9504. The linear equation may be used to estimate the octanol-water partition coefficient of other PAHs and similar H acceptors compounds. Being compared with Leo's method which was based on the additive-constitutive nature of the partition coefficient, the solid-phase microextraction method may distinguish efficiently Kow of the isomer.

Chromatography, Gas↗

PubMed1998

MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta.

A critical step in the signal-induced activation of the transcription factor NF-kappaB is the site-specific phosphorylation of its inhibitor, IkappaB, that targets the latter for degradation by the ubiquitin-proteasome pathway. We have previously shown that mitogen-activated protein kinase/ERK kinase kinase 1 (MEKK1) can induce both this site-specific phosphorylation of IkappaB alpha at Ser-32 and Ser-36 in vivo and the activity of a high molecular weight IkappaB kinase complex in vitro. Subsequently, others have identified two proteins, IkappaB kinase alpha (IKK-alpha) and IkappaB kinase beta (IKK-beta), that are present in a tumor necrosis factor alpha-inducible, high molecular weight IkappaB kinase complex. These kinases are believed to directly phosphorylate IkappaB based on the examination of the kinase activities of IKK immunoprecipitates, but more rigorous proof of this has yet to be demonstrated. We show herein that recombinant IKK-alpha and IKK-beta can, in fact, directly phosphorylate IkappaB alpha at Ser-32 and Ser-36, as well as homologous residues in IkappaB beta in vitro, and thus are bona fide IkappaB kinases. We also show that MEKK1 can induce the activation of both IKK-alpha and IKK-beta in vivo. Finally, we show that IKK-alpha is present in the MEKK1-inducible, high molecular weight IkappaB kinase complex and treatment of this complex with MEKK1 induces phosphorylation of IKK-alpha in vitro. We conclude that IKK-alpha and IKK-beta can mediate the NF-kappaB-inducing activity of MEKK1.

Amino Acid Sequence↗

PubMed1998

A comparison of root surface temperatures using different obturation heat sources.

This study compared root surface temperatures produced during warm vertical obturation using the System B Heat Source (SB), the Touch 'n Heat device (TH), and a flame-heated carrier (FH). The root canals of 30 maxillary incisor, premolar, and mandibular incisor teeth were prepared; divided into three groups; and obturated using each heat source. A thermocouple placed 2 mm below the cementoenamel junction transferred the temperature rise on the external root surface to a digital thermometer. SB surface temperature rise was < 10 degrees C for all experimental teeth. TH temperature rise in maxillary incisors and premolars was < 10 degrees C; however, > 10 degrees C was observed for mandibular incisors. FH produced a > 10 degrees C surface temperature rise in all experimental teeth. The critical level of root surface heat required to produce irreversible bone damage is believed to be > 10 degrees C. The findings of this study suggest that warm vertical condensation with the SB should not damage supporting periradicular tissues. However, caution should be used with TH and FH on mandibular incisors.

Body Temperature↗

PubMed1998

Gender-specific effects of medicinal drugs on hearing levels of older persons.

As part of a large-scale study of presbyacusis, responses to a medicinal drug questionnaire from 85 female and 126 male human subjects were analyzed. Medicinal drugs were divided into 35 categories based on their pharmacologic effects. Subjects' ages ranged from 60 to 82 years. At least 10% of subjects reported taking drugs in 14 of 35 categories. Results were significantly different between female and male subjects. In men, none of the 14 categories showed a statistically significant relation to the pure-tone average (PTA) of 500, 1000, 2000, and 4000 Hz. In women, 3 of the 14 categories showed a statistically significant relation to the PTA. First, the average PTA of female subjects taking beta-adrenergic medication was 20 dB higher (poorer) than those not taking beta-adrenergic medication. Second, women taking antihistamine/cold preparations had an average PTA 9 dB higher (poorer) than those not taking antihistamine/cold preparations. Third, the average PTA of women taking calcium-channel blockers (CCBs) was 12 dB lower (better) than those not taking CCBs. In men, however, these drugs produced effects on the PTA of less than 3 dB. Differences between women and men were not explainable by differences in age or hearing level.

Adrenergic beta-Agonists↗

PubMed1998

Analysis of blood chemistry and hearing levels in a sample of older persons.

OBJECTIVE: As part of an ongoing study of presbyacusis, the relationship between blood chemistry levels and hearing levels was investigated. Previous reports often used small sets of blood chemistry measures, and results were inconclusive. This experiment examined hearing levels and 27 measures of blood chemistry using various univariate and multivariate statistical procedures. DESIGN: Blood from 89 female and 128 male human subjects was collected. Subjects' ages ranged from 60 to 82 yr, and hearing levels ranged from normal to moderate/severe. Subjects with a history of middle ear disease were excluded. Electrolyte panel (Na, K, Cl, CO2, Ca, urea nitrogen, glucose, creatinine, and Mg), hematology panel (WBC, RBC, Hgb, hematocrit, platelet, etc.), serum lipids (total cholesterol, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]), immunoglobulins (IgG, IgA, IgM, and IgE), and thyroxine were analyzed using univariate and multivariate statistical procedures. RESULTS: Blood chemistry levels of most subjects were within normal ranges as defined by our laboratory. Correlation between blood chemistry measures and pure-tone averages (PTAs) ranged from minimal to low. Results of factor analysis, discriminant analysis, and canonical analysis showed that combining blood chemistry measures from the same panel still could not predict PTA effectively. One exception to this was a gender-specific effect of cholesterol. Hearing levels of women with high LDL/HDL ratios were 5 dB better than those of women with low LDL/HDL ratios. The comparable difference in men was only 1 dB. CONCLUSION: Results suggest that blood chemistry measures that are primarily within the normal range have very little value in predicting pure-tone thresholds in older subjects.

Age Factors↗

PubMed1998

[Measurements of Ar(I) excitation temperatures and electron number densities in an ICP with and without the presence of Freon 12--the development of ICP technology for hazardous waste management].

For the management of refractory hazardous wastes, an innovative technology emerging recently is the application of ultra high temperature plasma. The preliminary study on destruction of Freon 12 by ICP (1-2kW) under a joint program between Xiamen Univ. and Hong Kong Baptist Univ. showed that the ICP technology indeed holds a great potential for hazardous wastes management. The destruction efficiency is more than 99.9999%. With and without the presence of Freon 12, Ar(I) excitation temperatures were measured by Boltzmann plot method and electron number densities the by H (beta) line broadening method. It was found that above the load coil, the excitation temperatures and electron number densities decrease with increasing the amount of Freon 12 presented in the central channel of the ICP, but inside the load coil region, the excitation temperatures are affected little by Freon 12. The conclusion of thermal pinch could be expected from this phenomenon.

Argon↗