Biomedical subjects

S Ahn

Publications and source records attributed to S Ahn.

At least 19 recordsLinked to original sources

PubMed2004

Aperture maneuver with compelled breath (AMC) for moving tumors: a feasibility study with a moving phantom.

Respiration causes target motion, which is known to be one of the technical bottlenecks in radiotherapy, especially for stereotactic radio-surgery and intensity modulated radiotherapy (IMRT). To overcome this problem, aperture maneuver with compelled breath (AMC) has been developed. In order to simulate compelled respiratory motion, a moving phantom using a ventilator was designed. As the air flow was forced to the bellows, which simulates the lungs, by a ventilator, a film connected to the ventilator moved like the respiratory target motion. A software was developed to transfer multileaf collimator motion from breathless to actual periodic breathing conditions. Static fields as well as step-and-shoot IMRT fields were modified in accordance with moving shapes to follow the target position, using the software with the controlled breathing information. Film dosimetry for a small field and for IMRT fields with a moving phantom was performed. To evaluate clinical implementation, five healthy volunteers were tested to breathe through a ventilator, and all of them could adapt the compelled breath without any difficulties. Additive margins for a moving target with AMC were not larger than 3 mm for respiratory organ motions up to 18 mm, while those with the static beam were 9 mm. For IMRT fields, large discrepancies were present between a static target and a moving target with the static beam, while they coincided well with AMC. Clinical acceptable differences between the dose distributions from a static target with the static beam and from a moving target with AMC revealed that this technique could be applied clinically.

Algorithms↗

PubMed2004

A feasibility study on the prediction of tumour location in the lung from skin motion.

The system for predicting tumour location from skin motion induced by respiration was designed to reduce the effects of target movement. Fluoroscopic studies on 34 sites in the lungs and 14 sites in the diaphragm were performed so that the motions of skin markers and organs could be observed simultaneously. While patients were lying down in the simulator with radio-opaque markers on their skin, fluoroscopic images both in the anterior-posterior (AP) view and in the lateral view were sent to an analysing computer and recorded. The results that showed a strong correlation (0.77+/-0.12) between the patients' skin and tumour movement, especially for the sites located in the lower lung fields or in the diaphragm. With the prediction from skin motion, the uncertainties of the position of tumours due to respiratory movement could be reduced by up to 1.47 cm in the lower lung fields in the superior-inferior (SI) direction. This study revealed that it is possible to trace the exact location of tumours in the lungs by observing skin motion in most cases (up to 88%).

Feasibility Studies↗

PubMed2003

Independent modulation of basal and feeding-evoked dopamine efflux in the nucleus accumbens and medial prefrontal cortex by the central and basolateral amygdalar nuclei in the rat.

Interactions of the central and basolateral nuclei of the amygdala with the mesocorticolimbic dopamine system are implicated in the acquisition and performance of conditioned responses for food reward. This study investigated whether dopamine transmission in the nucleus accumbens and the medial prefrontal cortex of the rat is influenced by the amygdala and if so, to assess the significance of the interaction in free feeding of a palatable food. To this end, we examined the effects of reverse-dialysis of the sodium channel blocker lidocaine into either the central or basolateral on dopamine efflux in the nucleus accumbens and the medial prefrontal cortex as determined by microdialysis and high-pressure liquid chromatography with electrochemical detection. The present results revealed for the first time that inactivation of the central decreased basal levels of dopamine efflux in the nucleus accumbens, but not in the medial prefrontal cortex. Furthermore, administration of lidocaine into the central significantly attenuated feeding-evoked increases in dopamine efflux in both terminal regions. These neurochemical effects were accompanied by feeding-related behaviours akin to the Klüver-Bucy syndrome. In contrast, inactivation of the basolateral affected neither food intake nor dopamine efflux in the nucleus accumbens, but triggered dramatic long-lasting oscillations in dopamine efflux in the medial prefrontal cortex, irrespective of whether food was presented or not. Overall, these findings indicate that the central and basolateral independently modulate dopamine transmission in both terminal regions of the mesocorticolimbic dopamine system. The central, in particular, and its influence on the dopamine system, may be involved in the regulation of food intake.

Amygdala↗

PubMed2003

Factors influencing the fracture of nickel-titanium rotary instruments.

AIM: To evaluate the effect of rotational speed and the angle and radius of curvature of root canals on the fracture of two types of nickel-titanium rotary instruments: K3 and ProTaper. METHODOLOGY: A total of 240 root canals of extracted human maxillary and mandibular molars were divided into two groups of 120, according to the angle of the canal curvature (group A: <30 degrees, group B: >30 degrees). Each group was then divided into two subgroups of 60 canals in order to perform instrumentation using K3 and ProTaper rotary instruments at three different rotational speeds: 150, 250 and 350 r.p.m. (20 canals at each rotational speed). Each instrument was used a maximum of 20 times and at one rotational speed only. The angle and radius of canal curvature were measured in the only group in which fractures actually took place (group B). RESULTS: There were a total of 22 instrument fractures; all of these occurred in canals with curves >30 degree. In a multivariate analysis, it was demonstrated that the files used at a rotational speed of 350 r.p.m. were more likely to fracture than those used at 250 r.p.m. (OR: 1113.88; 95% CI: 2.36-526420.05) and than those used at 150 r.p.m. (OR: 13531.33; 95% CI: 5.37-34120254.00). A decrease in the angle of curvature of the canal also significantly reduced the likelihood of fracture (OR: 0.2083; 95% CI: 0.068-0.6502). These relationships remained significant after being adjusted for the potential interactions between the remaining variables. No significant differences were found between the files or the radii of the canals. CONCLUSIONS: Instrument fracture was associated with rotational speed and the angle of curvature of the canal.

Dental Alloys↗

PubMed2002

Identification of Escherichia coli O157:H7 and other enterohemorrhagic serotypes by EHEC- hlyA targeting, strand displacement amplification, and fluorescence polarization.

Human disease caused by enterohemorrhagic E. coli O157:H7 and other serotypes (EHEC) has been associated with bovine fecal contamination of food and the environment. The range of serotypes, low infectious dose, and numerous transmission vehicles for EHEC render development of detection methods for this pathogen complex. In this study, the hemolysin gene (EHEC- hly A) was targeted with oligonucleotides, and probe-target hybrids were amplified using strand displacement amplification (SDA). Amplicons were resolved in the complete reaction mix through changes in the fluorescence polarization (FP) of a fluorescein-labeled detector probe hybridized to the amplicons during amplification. Results combining EHEC- hly A, SDA, and FP were obtained within 35 min of reaction initiation. The test specificity was determined on EHEC strains representing 13 serotypes (49 isolates); and control uropathogenic, commensal, and other organisms (10 isolates). Statistical analysis of results indicated a sensitivity in the reaction vessel to 4.3 bacteria (95% confidence interval), and a specificity for EHEC (n=59) at 100% (P=5.11E-17; i.e. P<<0.05). Detection based on combining EHEC- hly A, SDA, and FP was compatible with water sources directly associated with human infection (drinking and recreational supplies), and bovine drinking trough water representing an environmental matrix linked to the maintenance of an EHEC animal reservoir.

Animals↗

PubMed2001

The "open" and "closed" structures of the type-C inorganic pyrophosphatases from Bacillus subtilis and Streptococcus gordonii.

Recently, a new class of soluble inorganic pyrophosphatase (type-C PPase) has been described that is not homologous in amino acid sequence or kinetic properties to the well-studied PPases (types A and B) found in many organisms from bacteria to humans and thought to be essential to the cell. Structural studies of the type-C PPases from Streptococcus gordonii and Bacillus subtilis reveal a homodimeric structure, with each polypeptide folding into two domains joined by a flexible hinge. The active site, formed at the interface between the N and C-terminal domains, binds two manganese ions approximately 3.6 A apart in a conformation resembling binuclear metal centres found in other hydrolytic enzymes. An activated water molecule bridging the two metal ions is likely poised for nucleophilic attack of the substrate. Importantly, the S. gordonii and B. subtilis enzymes have crystallised in strikingly different conformations. In both subunits of the S. gordonii crystal structure (1.5 A resolution) the C-terminal domain is positioned such that the active site is occluded, with a sulphate ion bound in the active site. In contrast, in the B. subtilis structure (3.0 A resolution) the C-terminal domain is rotated by about 90 degrees, leaving the active site wide open and accessible for substrate binding.

Amino Acid Sequence↗

PubMed2001

Cardiac and hemodynamic effects of intravenous dofetilide in patients with heart failure.

This study assesses the effects of dofetilide, a new selective Ikr blocker with class III properties, on left ventricular function and hemodynamics of heart failure and compares these effects with those of placebo and amiodarone. Because available antiarrhythmic drugs may depress myocardial performance, an invasive hemodynamic study was performed to assess the safety of this agent. Hemodynamic and angiographic data were obtained at baseline and after 30 minutes of double-blind infusion of dofetilide (8 microg/kg; n = 12), placebo (n = 12), or amiodarone (5 mg/kg; n = 6) in heart failure patients (New York Heart Association class II or III, ejection fraction <35%). Intravenous dofetilide preserved the inotropic indexes and the end-systolic volume index despite a slight but significant decrease in heart rate, whereas intravenous amiodarone increased end-diastolic and end-systolic volume indexes. Amiodarone induced a negative inotropic effect illustrated by a rightward shift of the pressure-volume loop and a reduction in pressure-derived indexes of contractility. Intravenous dofetilide acutely prolonged QT interval more than intravenous amiodarone; however, dofetilide did not slow the overall relaxation rate and reduced QT dispersion. In an acute setting, compared with intravenous amiodarone, intravenous dofetilide preserves cardiac function offering a hemodynamic advantage to treat arrhythmias in patients with impaired left ventricular function.

Adult↗

PubMed2001

Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein-coupled receptors: a co-culture system for identifying intermediates upstream and downstream of heparin-binding EGF shedding.

"Transactivation" of epidermal growth factor receptors (EGFRs) in response to activation of many G protein-coupled receptors (GPCRs) involves autocrine/paracrine shedding of heparin-binding EGF (HB-EGF). HB-EGF shedding involves proteolytic cleavage of a membrane-anchored precursor by incompletely characterized matrix metalloproteases. In COS-7 cells, alpha(2A)-adrenergic receptors (ARs) stimulate ERK phosphorylation via two distinct pathways, a transactivation pathway that involves the release of HB-EGF and the EGFR and an alternate pathway that is independent of both HB-EGF and the EGFR. We have developed a mixed culture system to study the mechanism of GPCR-mediated HB-EGF shedding in COS-7 cells. In this system, alpha(2A)AR expressing "donor" cells are co-cultured with "acceptor" cells lacking the alpha(2A)AR. Each population expresses a uniquely epitope-tagged ERK2 protein, allowing the selective measurement of ERK activation in the donor and acceptor cells. Stimulation with the alpha(2)AR selective agonist UK14304 rapidly increases ERK2 phosphorylation in both the donor and the acceptor cells. The acceptor cell response is sensitive to inhibitors of both the EGFR and HB-EGF, indicating that it results from the release of HB-EGF from the alpha(2A)AR-expressing donor cells. Experiments with various chemical inhibitors and dominant inhibitory mutants demonstrate that EGFR-dependent activation of the ERK cascade after alpha(2A)AR stimulation requires Gbetagamma subunits upstream and dynamin-dependent endocytosis downstream of HB-EGF shedding and EGFR activation, whereas Src kinase activity is required both for the release of HB-EGF and for HB-EGF-mediated ERK2 phosphorylation.

Animals↗

PubMed2001

Chiral recognition in gas-phase cyclodextrin: amino acid complexes--is the three point interaction still valid in the gas phase?

The validity of the "three-point interaction" model is examined in the guest exchange reaction involving complexes of cyclodextrins and amino acids. The amino acid guest is exchanged in the gas phase in the presence of a gaseous alkyl amine. The net reaction is proton transfer between the protonated amino acid and the alkyl amine. The amino acid is lost as a neutral species. This reaction is sensitive to the chirality of the amino acid. Several amino acids are examined as well as the respective methyl esters to determine the role of the three interacting groups (ammonium, carboxylic acid, and side chain) in enantioselectivity. We find that the three-point interaction model is indeed valid in the gas phase. Enantioselectivity is optimal when two points of attraction and one repulsion is present in the gas-phase complex. The results are supported by molecular modeling calculations. A mechanism for the exchange is proposed.

Amines↗

PubMed2000

High-resolution, >1 GHz NMR in unstable magnetic fields.

Resistive or hybrid magnets can achieve substantially higher fields than those available in superconducting magnets, but their spatial homogeneity and temporal stability are unacceptable for high-resolution NMR. We show that modern stabilization and shimming technology, combined with detection of intermolecular zero-quantum coherences (iZQCs), can remove almost all of the effects of inhomogeneity and drifts, while retaining chemical shift differences and J couplings. In a 25-T electromagnet (1 kHz/s drift, 3 kHz linewidth over 1 cm(3)), iZQC detection removes >99% of the remaining inhomogeneity, to generate the first high-resolution liquid-state NMR spectra acquired at >1 GHz.

Chemical Phenomena↗

PubMed2000

Resurrection of crushed magnetization and chaotic dynamics in solution NMR spectroscopy.

We show experimentally and theoretically that two readily observed effects in solution nuclear magnetic resonance (NMR)-radiation damping and the dipolar field-combine to generate bizarre spin dynamics (including chaotic evolution) even with extraordinarily simple sequences. For example, seemingly insignificant residual magnetization after a crusher gradient triggers exponential regrowth of the magnetization, followed by aperiodic turbulent spin motion. The estimated Lyapunov exponent suggests the onset of spatial-temporal chaos and the existence of chaotic attractors. This effect leads to highly irreproducible experimental decays that amplify minor nonuniformities such as temperature gradients. Imaging applications and consequences for other NMR studies are discussed.

Journal Article↗

PubMed2000

Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism.

Neuronal nitric oxide (NO) synthase (nNOS) is dynamically regulated in response to a variety of physiologic and pathologic stimuli. Although the dynamic regulation of nNOS is well established, the molecular mechanisms by which such diverse stimuli regulate nNOS expression have not yet been identified. We describe experiments demonstrating that Ca(2+) entry through voltage-sensitive Ca(2+) channels regulates nNOS expression through alternate promoter usage in cortical neurons and that nNOS exon 2 contains the regulatory sequences that respond to Ca(2+). Deletion and mutational analysis of the nNOS exon 2 promoter reveals two critical cAMP/Ca(2+) response elements (CREs) that are immediately upstream of the transcription start site. CREB binds to the CREs within the nNOS gene. Mutation of the nNOS CREs as well as blockade of CREB function results in a dramatic loss of nNOS transcription. These findings suggest that nNOS is a Ca(2+)-regulated gene through the interactions of CREB on the CREs within the nNOS exon 2 promoter and that these interactions are likely to be centrally involved in the regulation of nNOS in response to neuronal injury and activity-dependent plasticity.

Animals↗

PubMed2000

Measurement of the W-->taunu production cross section in pp collisions at square root s=1.8 TeV.

We report on a measurement of sigma(pp-->W+X)B(W-->taunu) in pp collisions at sqrt[s]=1.8 TeV at the Fermilab Tevatron. The measurement is based on an integrated luminosity (lum) of 18 pb-1 of data collected with the D0 detector during 1994-1995. We find that sigma(pp-->W+X)B(W-->taunu)=2.22+/-0.09 (stat)+/-0. 10 (syst)+/-0.10 (lum) nb. Lepton universality predicts that the ratio of the tau and electron electroweak charged current couplings to the W boson, gWtau/gWe, be unity. We find gWtau/gWe=0.980+/-0.031, in agreement with lepton universality.

Journal Article↗

PubMed2000

beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis.

beta-Arrestins can act as adapter molecules, coupling G-protein-coupled receptors to proteins involved in mitogenic as well as endocytic pathways. We have previously identified c-SRC as a molecule that is rapidly recruited to the beta2-adrenergic receptor in a beta-arrestin1-dependent manner. Recruitment of c-SRC to the receptor appears to be involved in pathways leading to receptor internalization and mitogen-activated protein kinase activation. This recruitment of c-SRC to the receptor involves an interaction between the amino-terminal proline-rich region of beta-arrestin1 and the Src homology 3 (SH3) domain of c-SRC, but deletion of the proline-rich domain does not totally ablate the interaction. We have found that a major interaction also exists between beta-arrestin1 and the catalytic or kinase domain (SH1) of c-SRC. We therefore hypothesized that a catalytically inactive mutant of the isolated catalytic subunit, SH1(kinase dead) (SH1(KD)), would specifically block those cellular actions of c-SRC that are mediated by beta-arrestin1 recruitment to the G-protein-coupled receptor. In contrast, the majority of cellular phosphorylations catalyzed by c-SRC, which do not involve interaction with the SH1 domain, would be predicted to be unaffected. The SH1(KD) mutant did indeed block beta2-adrenergic receptor internalization and receptor-stimulated tyrosine phosphorylation of dynamin, actions previously shown to be c-SRC-dependent. In contrast, SAM-68 and whole cell tyrosine phosphorylation by c-SRC was unaffected, indicating that the SH1(KD) mutant did not inhibit c-SRC tyrosine kinase activity in general. These results not only clarify the nature of the beta-arrestin1/c-SRC interaction but also implicate beta-arrestin1 as an important mediator of receptor internalization by recruiting tyrosine kinase activity to the cell surface to phosphorylate key endocytic intermediates, such as dynamin.

Arrestins↗

PubMed2000

The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor.

Many G protein-coupled receptors (GPCRs) activate MAP kinases by stimulating tyrosine kinase signaling cascades. In some systems, GPCRs stimulate tyrosine phosphorylation by inducing the "transactivation" of a receptor tyrosine kinase (RTK). The mechanisms underlying GPCR-induced RTK transactivation have not been clearly defined. Here we report that GPCR activation mimics growth factor-mediated stimulation of the epidermal growth factor receptor (EGFR) with respect to many facets of RTK function. beta(2)-Adrenergic receptor (beta(2)AR) stimulation of COS-7 cells induces EGFR dimerization, tyrosine autophosphorylation, and EGFR internalization. Coincident with EGFR transactivation, isoproterenol exposure induces the formation of a multireceptor complex containing both the beta(2)AR and the "transactivated" EGFR. beta(2)AR-mediated EGFR phosphorylation and subsequent beta(2)AR stimulation of extracellular signal-regulated kinase (ERK) 1/2 are sensitive to selective inhibitors of both EGFR and Src kinases, indicating that both kinases are required for EGFR transactivation. beta(2)AR-dependent signaling to ERK1/2, like direct EGF stimulation of ERK1/2 activity, is sensitive to inhibitors of clathrin-mediated endocytosis, suggesting that signaling downstream of both the EGF-activated and the GPCR-transactivated EGFRs requires a productive engagement of the complex with the cellular endocytic machinery. Thus, RTK transactivation is revealed to be a process involving both association of receptors of distinct classes and the interaction of the transactivated RTK with the cells endocytic machinery.

Animals↗

PubMed2000

Intermolecular zero-quantum coherence imaging of the human brain.

The first intermolecular zero-quantum coherence (iZQC) MR images of the human brain at 4T are presented. To generate iZQC images, a modified echo-planar imaging pulse sequence was used which included an additional 45 degrees RF pulse and a correlation gradient. The observability and nonconventional contrast of human brain iZQC images at 4T is demonstrated. Axial images are presented for various pulse sequence parameters, and a zero-quantum relaxation map is obtained.

Brain↗

PubMed2000

"Malgun" (clear) cell change of gastric epithelium in chronic Helicobacter pylori gastritis.

To characterize the Helicobacter pylori gastritis-associated epithelial change, we analyzed 251 randomly selected gastric biopsies. The "malgun" (clear) cell change of the gastric epithelium was noted in 229 biopsies (91.2%). Malgun cells were characterized by large, pale nuclei with a euchromatin pattern, enlarged nucleoli, and clear cytoplasm. In the proliferative zone, individual malgun cells and small clusters were often in close contact with infiltrating neutrophils, suggesting that they had developed individually in the background of acute foveolitis. Mitotic figures of malgun cells were not infrequent, including atypical ones. In the surface epithelium, most malgun cells were in clusters that were often large enough to occupy wide epithelial segments. With Warthin-Starry triple staining, they were distinguished by the absence of silver impregnation, while other cells showed staining of the heterochromatin. They displayed prominent immunostaining for low molecular weight cytokeratin (No. 8). Most malgun cells were PCNA-positive in both surface and proliferative zones, whereas Ki67-positive cells were found only in the proliferative zone. It was suggested that a population of malgun cells, which were positive for PCNA only, were in the process of active DNA repair. The malgun cell change may represent a "cellular pattern of activation" in a population which had significant DNA damage, but somehow escaped the detection by the apoptosis system. The notion of "damage at the genetic level" was supported by the observation that these cells remained at least for 8 weeks after eradication of the H. pylori infection.

Adult↗

PubMed2000

A pilot survey of aberrant drug-taking attitudes and behaviors in samples of cancer and AIDS patients.

The clinical assessment of drug-taking behaviors in medically ill patients with pain is complex and may be hindered by the lack of empirically derived information about such behaviors in particularly medically ill populations. To investigate issues surrounding the assessment of these behaviors, we piloted a questionnaire based on the observations of specialists in pain management and substance abuse. This preliminary questionnaire evaluated medication use, present and past drug abuse, patients' beliefs about the risk of addiction in the context of pain treatment, and aberrant drug-taking attitudes and behaviors. This instrument was piloted in a mixed group of cancer patients (N = 52) and a group of women with HIV/AIDS (N = 111). Reports of past drug use and abuse were more frequent than present reports in both groups. Current aberrant drug-related behaviors were seldom reported, but attitude items revealed that patients would consider engaging in aberrant behaviors, or would possibly excuse them in others, if pain or symptom management were inadequate. Aberrant behaviors and attitudes were endorsed more frequently by the women with HIV/AIDS than by the cancer patients. Patients greatly overestimated the risk of addiction in pain treatment. We discuss the significance of these findings and the need for cautious interpretation given the limitations of the methodology. This early experience suggests that both cancer and HIV/AIDS patients appear to respond in a forthcoming fashion to drug-taking behavior questions and describe attitudes and behaviors that may be highly relevant to the diagnosis and understanding management of substance use among patients with medical illness.

Acquired Immunodeficiency Syndrome↗