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Biomedical subjects

S A Lee

Publications and source records attributed to S A Lee.

At least 19 recordsLinked to original sources
PubMed2002

Experimental studies on the nature of bonding of DNA*bipyridyl-(ethylenediamine)platinum(II) and DNA*netropsin complexes in solution and oriented wet-spun films.

The stability of complexes of NaDNA with bipyridyl- (ethylenediamine)platinum(II) (abbreviated [(bipy)Pt(en)](2+)) and with netropsin has been studied using two techniques: (i) ultraviolet (UV) melting experiments were done on NaDNA* [(bipy)Pt(en)](2+), showing that the [(bipy)Pt(en)](2+) ligand stabilizes the DNA double helix structure; and (ii) swelling measurements (via optical microscopy) as a function of relative humidity were done on wet-spun oriented films of NaDNA*[(bipy)Pt(en)](2+) and of NaDNA*netropsin. The swelling data shows that an irreversible transition of the films occurs at high relative humidity, first for the NaDNA*netropsin, then for pure NaDNA, and lastly for the NaDNA*[(bipy)Pt(en)](2+). These results are indicative that the [(bipy)Pt(en)](2+) complex stabilizes the intermolecular bonds which mediate the film swelling characteristics. A model is suggested for the binding of [(bipy)Pt(en)](2+) to DNA to explain why the swelling experiments show this ligand as increasing the intermolecular bond strength between the DNA double helices, while netropsin decreases this degree of stabilization.

2,2'-Dipyridyl↗
PubMed2002

Differential scanning calorimetric study of the binding of the primary water of hydration to nucleosides.

Differential scanning calorimetry was used to study the water of hydration of all of the nucleosides at 59% relative humidity. Hydration was observed in pristine samples of guanosine, (rG), deoxyguanosine, (dG), and deoxyadenosine, (dA). Two inequivalent water sites were observed in dG and one site in rG. Re-hydration was observed in rG and dG, but not in dA. The activation energies for rG were 0.697 +/- 0.051 eV and 0.683 plus minus 0.090 eV for pristine and cycled samples respectively. dG had activation energies of 0.726 +/- 0.026 eV and 0.997 +/- 0.034 eV for the first and second peaks in the pristine samples while the activation energy for cycled dG was 0.671 +/- 0.133 eV.

Binding Sites↗
PubMed2002

Raman and infrared studies of nucleosides at high pressures: II. Cytidine.

Raman and mid-infrared (MIR) spectra have been recorded for crystalline cytidine at pressures up to 10 GPa at room temperature. Broadening and positive wavenumber shifts are observed for most of the Raman and MIR peaks with increasing pressure. However, some of the MIR peaks associated with hydrogen-stretching modes display a negative wavenumber shift as a result of charge transfer effects. Evidence of a phase transition near 4 GPa is presented and attributed to a change in the conformation of the five membered sugar ring.

Cold Temperature↗
PubMed2001

Vaccine-induced antibodies to the native, oligomeric envelope glycoproteins of primary HIV-1 isolates.

A simple and sensitive method for measuring antibodies to primary human immunodeficiency virus type 1 (HIV-1) isolates has been developed. The flow cytometric immuno-fluorescence assay detects antibodies that bind to the native, oligomeric form of the envelope glycoprotein (gp120) expressed on the surface of PM-1 cells infected with primary isolates of HIV-1. Sera from people infected with HIV-1 or those immunized with recombinant gp120 vaccines were tested. Significant correlation was observed between neutralizing activity and oligomeric gp120 binding activity. Thirteen to 100% of individuals immunized with the subtype B bivalent vaccine AIDSVAX B/B developed oligomeric gp120 binding antibodies against a variety of subtype B primary isolates. For several isolates, AIDSVAX B/B sera reacted better than monovalent AIDSVAX B sera, suggesting that addition of the second immunogen improved the breadth of the antibody response. Cross-subtype binding activities, induced by AIDSVAX B/B, were lower than activities to subtype B isolates, suggesting that additional immunogen(s) may be desirable in vaccine(s) formulated for geographic regions where non-B subtypes are dominant.

AIDS Vaccines↗
PubMed2001

Role of ATM in oxidative stress-mediated c-Jun phosphorylation in response to ionizing radiation and CdCl2.

Ionizing radiation-induced phosphorylation of the transcription factor c-Jun is impaired in cells derived from individuals with ataxia telangiectasia (AT), in which the ATM gene is mutated. We demonstrate here that ATM modulates c-Jun phosphorylation following exposure to ionizing radiation as well as treatment with CdCl(2), a potent pro-oxidant. Exposure of AT and control fibroblasts to CdCl(2) induced a biphasic increase in c-Jun phosphorylation on serine residues 63 and 73, with the extent of the second phase being markedly greater in AT cells than in control cells. Heme oxygenase-1, a marker of oxidative stress, was also significantly induced in AT fibroblasts. Expression of recombinant ATM in AT fibroblasts, however, reduced the extent of the effects of CdCl(2) on both c-Jun phosphorylation and heme oxygenase-1 induction. Our data suggest that ATM contributes to oxidative stress-mediated signaling that leads to c-Jun phosphorylation by acting as a sensor of ionizing radiation-induced oxidative stress and by modulating intracellular redox homeostasis.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2001

Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140.

The biologically active form of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein is oligomeric. We previously described a soluble HIV-1 IIIB Env protein, gp140, with a stable oligomeric structure composed of uncleaved gp120 linked to the ectodomain of gp41 (P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss, J. Virol. 68:3015-3026, 1994). Here we compared the antibody responses of rabbits to gp120 and gp140 that had been produced and purified in an identical manner. The gp140 antisera exhibited enhanced cross-reactivity with heterologous Env proteins as well as greater neutralization of HIV-1 compared to the gp120 antisera. To examine both immunogenicity and protective efficacy, we immunized rhesus macaques with oligomeric gp140. Strong neutralizing antibodies against a homologous virus and modest neutralization of heterologous laboratory-adapted isolates were elicited. No neutralization of primary isolates was observed. However, a substantial fraction of the neutralizing activity could not be blocked by a V3 loop peptide. After intravenous challenge with simian-HIV virus SHIV-HXB2, three of the four vaccinated macaques exhibited no evidence of virus replication.

AIDS Vaccines↗
PubMed2000

Calmodulin-dependent activation of p38 and p42/44 mitogen-activated protein kinases contributes to c-fos expression by calcium in PC12 cells: modulation by nitric oxide.

Calcium and nitric oxide (NO) are important messengers for the activity-dependent immediate-early gene (IEG) expressions in neuronal cells. In the present study, we have investigated the roles of two mitogen-activated protein (MAP) kinases, extracellular signal-regulated protein kinase (ERK) and p38 MAP kinase (p38 kinase) in calcium- and NO-induced c-fos expression in PC12 cells. Membrane depolarization-induced calcium increases activated both ERK and p38 kinase within 5 min. The activation of both ERK and p38 kinase by calcium was a calmodulin-dependent process since the pretreatment of W13 or calmidazolium, specific calmodulin antagonists, blocked calcium-induced activation of both MAP kinases. Calcium-induced c-fos expression was significantly reduced by the pretreatment of either MEK inhibitor (PD98059) or p38 kinase inhibitor (SB203580). This finding indicates that the calmodulin-dependent activation of ERK and p38 kinase is involved in calcium-induced c-fos expression. However, sodium nitroprusside and SIN-1, known to release NO, dose-dependently activated only ERK. NO-induced c-fos expression was partially inhibited by the PD98059. We also observed that NO dose-dependently potentiates not only calcium-induced c-fos expression but also calcium-induced ERK activation. In the presence of PD98059, the amplification of calcium-induced c-fos expression by NO was not observed. This result suggests that calcium- and NO-signals converge into the MEK/ERK pathway, thereby enhance IEG expressions in neuronal cells.

Animals↗
PubMed2000

Complications and results of subdural grid electrode implantation in epilepsy surgery.

BACKGROUND: We assessed the risk of delayed subdural hematoma and other complications associated with subdural grid implantation. METHODS: Forty-nine patients underwent subdural grid implantation with/without subdural strips or depth electrodes from January 1994 to August 1998. To identify the risk associated with subdural grid implantation, a retrospective review of all patients' medical records and radiological studies was performed. RESULTS: The major complications of 50 subdural grid electrode implantations were as follows: four cases (7.8%) of delayed subdural hematoma at the site of the subdural grid, requiring emergency operation; two cases (3.9%) of infection; one case (2.0%) of epidural hematoma; and one case (2.0%) of brain swelling. After subdural hematoma removal, the electrodes were left in place. CCTV monitoring and cortical stimulation studies were continued thereafter. No delayed subdural hematoma has occurred since routine placement of subdural drains was begun. CONCLUSIONS: In our experience the worst complication of subdural grid implantation has been delayed subdural hematoma. Placement of subdural drains and close observation may be helpful to prevent this serious complication.

Adolescent↗
PubMed2000

CD8(+) cell noncytotoxic anti-human immunodeficiency virus response inhibits expression of viral RNA but not reverse transcription or provirus integration.

CD8(+) T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in CD4(+) cells by a noncytotoxic mechanism that inhibits the expression of viral RNA. The present study examined whether other step(s) in the virus replicative cycle could be affected by the CD8(+) cells. Culturing HIV-infected CD4(+) T cells with antiviral CD8(+) T cells did not significantly reduce the amounts of (i) early HIV DNA reverse transcripts (detected by LTR-U3/R), (ii) total nuclear HIV gag DNA, or (iii) integrated proviral DNA. However, exposure to the CD8(+) T cells did cause a reduction in the amount of multiply spliced tat and full-length gag mRNA expressed by the infected CD4(+) T cells, confirming previous observations. The levels of glyceraldehyde-3-phosphate dehydrogenase and interleukin-2 receptor-alpha mRNA were not affected. The results support the conclusion that the noncytotoxic anti-HIV response of CD8(+) T cells, demonstrable in vitro, does not affect any of the virus replication steps leading to the integration of proviral HIV, but specifically interrupts the expression of viral RNA.

CD4-Positive T-Lymphocytes↗
PubMed2000

NaDNA-bipyridyl-(ethylenediamine)platinum (II) complex: structure in oriented wet-spun films and fibers.

Complexes of NaDNA with bipyridyl-(ethylenediamine)platinum(II) (abbreviated [(bipy)Pt(en)](2+)) in solid, oriented films, prepared with a wet-spinning method, have been studied using x-ray diffraction, elastic neutron scattering, two-dimensional magic-angle-spinning nuclear magnetic resonance (NMR), infrared (IR) linear dichroism, and IR absorption. All of these experiments indicate that the DNA in this complex is in the B conformation. The neutron diffraction experiments reveal that the rise per residue is 3.31 A, indicating that the [(bipy)Pt(en)](2+) molecular ion causes a small distortion of the B conformation. The neutron data in the direction perpendicular to the helical axis are consistent with a centered orthorhombic unit cell with a=22.65 A and b=32.2 A. The NMR and IR experiments show that the orientation of phosphate groups in the DNA small middle dot[(bipy)Pt(en)](2+) complex is the same as that observed for pure DNA in the B conformation. The IR experiments also show that the [(bipy)Pt(en)](2+) molecular ion stabilizes the B conformation of DNA down to 59% relative humidity, a low water activity. Mechanochemical experiments on wet-spun NaDNA fibers in 68% ethanol with and without [(bipy)Pt(en)](2+) reveal a 9% elongation of the DNA fibers as the complex is formed.

2,2'-Dipyridyl↗
PubMed2000

Intracranial EEG seizure-onset patterns in neocortical epilepsy.

PURPOSE: We investigated neocortical seizure-onset patterns recorded by intracranial EEG with regard to anatomic location, pathologic substrate, and prognostic value for surgical outcome. METHODS: Seizure onset was analyzed in 53 neocortical resective epilepsy surgery patients. Anatomic location was divided into temporal and extratemporal. Pathologic substrate was classified as developmental, mature, and negative or non-specific gliosis. Onset frequency was categorized by visual analysis into tradition EEG frequency bands. Spatial extent was divided into focal (fewer than four contacts) and regional (more than five contacts). Waveform at seizure onset was divided into several types based on their morphology. Onset features were examined with respect to anatomic location, pathologic substrate, and surgical outcome. RESULTS: Seizure-onset frequency was significantly related to spatial distribution and to anatomic location. Extratemporal and regional onset were more commonly in the gamma range, and temporal and focal onset in the beta frequency range or slower. Waveform could be categorized into five different patterns, of which low voltage fast activity (LVFA) was the most common form (57%). LVFA and rhythmic alpha-theta spike activity were more common in developmental than in mature pathology, whereas rhythmic sinusoidal waves at onset were found in only mature substrates. Waveform pattern showed a possible correlation with surgical outcome (p = 0.097): LVFA and rhythmic sinusoidal waves onset patterns were associated with favorable outcome more often (40.4%) than the other three patterns (6.3%). Slow onset suggested poor outcome in the subgroup of developmental pathology (p = 0.062). CONCLUSIONS: Certain electrographic seizure-onset features are associated with specific substrates and outcomes, whereas others reflect the anatomic location and its connections independent of the pathology.

Adolescent↗
PubMed1999

Raman and infrared studies of nucleosides at high pressures: I. Adenosine.

Room temperature Raman and infrared (IR) spectra of crystalline adenosine at pressures between 1 atm and 10 GPa are reported. Vibrational modes were identified through assignments in the literature. Many modes were found to increase in frequency with pressure; however, some irregularities were observed. Discontinuities were observed in numerous Raman and IR modes near 2.5 GPa, indicating a phase transition. The modes associated with the glycosidic bond shift significantly down in frequency near this pressure, suggesting a weakening of the associated bond. The IR modes associated with hydrogen-stretching motions were found to decrease in frequency with pressure.

Adenosine↗
PubMed1999

Mediation of a phase transition in hyaluronate films by the counterions Li, Cs, Mg and Ca as observed by infrared spectroscopy, optical microscopy and optical birefringence.

Infrared (IR) spectroscopy and optical microscopy have been performed as a function of relative humidity (rh) on wet-spun oriented films of hyaluronate (HA) prepared with various counterions. Complete swelling measurements have been obtained through optical microscopy for films of Cs-, Mg-, and CaHA. IR spectroscopy of Cs-, Mg-, Ca-, and LiHA films was performed for skeletal vibrations (800-1000 cm(-1)) and for vibrational modes (1150-1300 cm(-1)) attributed to C-C and C-O stretching modes and C-C-H and C-O-H bending modes. These techniques reveal evidence of a counterion-dependent phase transition occuring at high relative humidities. Optical birefringence measurements on the polycrystalline samples showed order before and disorder after the transition from lower to higher humidity.

Birefringence↗
PubMed1999

Clinical analysis of 12 Korean Lambert-Eaton myasthenic syndrome (LEMS) patients.

The Lambert-Eaton myasthenic syndrome (LEMS) heralds the occurrence of malignancy, especially small-cell lung cancer (SCLC), but it can also occur in the absence of cancer. Twelve patients were diagnosed as LEMS by clinical features and the classical electrophysiological triad, which includes a low amplitude of compound muscle action potentials (CMAP), decremental responses on low-rate stimulation, and incremental responses on high-rate stimulation on the repetitive nerve stimulation (RNS) test. There were 6 male and 6 female patients, ranging in age from 49 to 66 years. Malignancy(all were SCLC) was found in 7 patients. Males predominantly expressed the paraneoplastic form; whereas the primary autoimmune form was found only in women, who showed a good response to corticosteroid treatment. The neurological features were similar in both groups: proximal lower limb weakness, depressed muscle stretch reflexes, and dryness of mouth in nearly all patients. Bulbar dysfunction and limb paresthesia were a little more frequent in the paraneoplastic form. In RNS tests, the characteristic electrophysiological abnormalities were found in all patients and were more profound in the paraneoplastic form. We concluded that LEMS is commonly associated with malignancy, especially SCLC, but it should also be stressed that there are many female LEMS patients who do not harbor any malignancy at all, and that other treatment strategies such as immunotherapy should be considered for these patients.

Aged↗
PubMed1998

Impaired ionizing radiation-induced activation of a nuclear signal essential for phosphorylation of c-Jun by dually phosphorylated c-Jun amino-terminal kinases in ataxia telangiectasia fibroblasts.

The c-Jun amino-terminal kinases (JNKs) participate in intracellular signaling in response to cytokines and cellular stresses. JNKs are activated by phosphorylation on two critical residues, the threonine 183 and tyrosine 185, within the TPY motif. The activated JNKs, in turn, phosphorylate the nuclear protein c-Jun, a major component of the transcription factor AP1. In vitro studies have revealed a defect in ionizing radiation-induced activation of the JNK signaling pathway in lymphoblastoid cells from individuals with ataxia telangiectasia (AT). However, the biochemical basis for this signaling defect is not clear. Here, we show that ionizing radiation induces the phosphorylation of endogenous c-Jun in normal fibroblasts but not in AT fibroblasts. The p46 isoforms of dually phosphorylated JNKs were detected in the nuclei of both normal and AT fibroblasts following exposure to ionizing radiation or sham radiation. However, c-Jun kinase activity was detected in normal cells but not in AT cells. Furthermore, an exogenous purified active JNK protein was able to phosphorylate endogenous c-Jun in nuclear extracts only of normal cells and only after the cells were irradiated. Electrophoretic mobility shift assays also showed that the ionizing radiation-induced increase in the DNA binding activity of AP1 observed in normal cells was absent or markedly reduced in AT cell lines. These data suggest that the defect in ionizing radiation-induced signaling through c-Jun in AT cells is the result of impaired function of an unknown nuclear protein or proteins that negatively regulate both JNK and c-Jun.

Ataxia Telangiectasia↗