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Biomedical subjects

Y Chung

Publications and source records attributed to Y Chung.

At least 19 recordsLinked to original sources
PubMed2002

Effective mass anisotropy of gamma electrons in GaAs/AlGaAs quantum wells.

Resonant magnetotunneling in GaAs/Al(0.28)Ga0.72As double barrier structures is used to demonstrate that the effective mass of confined Gamma conduction electrons becomes anisotropic when an electric field is applied perpendicular to the interfaces. Although several authors have previously reported Gamma-related optical anisotropy, this is the first example of a corresponding electrical anisotropy. The results are explained using a quantum mechanical model involving interface band mixing that contains additional features not found in the optical case.

Journal Article↗
PubMed2001

Synthesis of highly crystalline and monodisperse maghemite nanocrystallites without a size-selection process.

The synthesis of highly crystalline and monodisperse gamma-Fe(2)O(3) nanocrystallites is reported. High-temperature (300 degrees C) aging of iron-oleic acid metal complex, which was prepared by the thermal decomposition of iron pentacarbonyl in the presence of oleic acid at 100 degrees C, was found to generate monodisperse iron nanoparticles. The resulting iron nanoparticles were transformed to monodisperse gamma-Fe(2)O(3) nanocrystallites by controlled oxidation by using trimethylamine oxide as a mild oxidant. Particle size can be varied from 4 to 16 nm by controlling the experimental parameters. Transmission electron microscopic images of the particles showed 2-dimensional and 3-dimensional assembly of particles, demonstrating the uniformity of these nanoparticles. Electron diffraction, X-ray diffraction, and high-resolution transmission electron microscopic (TEM) images of the nanoparticles showed the highly crystalline nature of the gamma-Fe(2)O(3) structures. Monodisperse gamma-Fe(2)O(3) nanocrystallites with a particle size of 13 nm also can be generated from the direct oxidation of iron pentacarbonyl in the presence of oleic acid with trimethylamine oxide as an oxidant.

Journal Article↗
PubMed2001

Haloperidol and clozapine increase neural activity in the rat prefrontal cortex.

Haloperidol and clozapine have been widely used to alleviate schizophrenic symptoms, but their physiological effects in the prefrontal cortex (PFC) are not known. Effects of haloperidol and clozapine on single unit activity were investigated in the medial PFC of anesthetized rats. Injection (intraperitoneal) of haloperidol (1 mg/kg) or clozapine (20 mg/kg) significantly elevated discharge rates of PFC neurons. Considering that hypofrontality is one characteristic of schizophrenic symptoms, these results raise the possibility that enhancement of PFC neural activity contributes to therapeutic effects of haloperidol and clozapine.

Action Potentials↗
PubMed2001

Mechanism of refractory ceramic fiber- and rock wool-induced cytotoxicity in alveolar macrophages.

OBJECTIVES: Man-made vitreous fibers (MMVFs) can induce cytotoxicity in a way similar to that of other particles, including silica and asbestos fibers. However, as yet the mechanism of MMVF-induced cytotoxicity is still not clear. This report aims to clarify the mechanism of MMVF-induced cytotoxicity in the alveolar macrophage (AM). In this mechanism, an attempt to prove the involvement of the adenosine triphosphate (ATP) generation system and the polyinosinic acid-inhibitable scavenger receptors was made. METHODS: Several parameters were observed for cytotoxicity, such as cell viability, the release of lactic dehydrogenase (LDH) and ATP levels in rat AM's that were treated with refractory ceramic fibers (RF2) and rock wool (RW1). A specially designed ATP generation system was used to determine the effect of MMVF on ATP generation. A scavenger receptor ligand was applied to evaluate the relationship between scavenger receptors and MMVF-induced ATP depletion. RESULTS: A 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that both RF2 and RW1 caused a decrease in cell viability and this decrease was concentration-dependent. RF2 and RW1 increased the release of LDH with increasing fiber concentration. From these parameters, RF2 was shown to exhibit greater cytotoxicity than did RW1. Both fibers decreased the intracellular ATP content and this decrease was concentration-dependent. The decrease was more pronounced in RW1 than in RF2 at all fiber concentrations. These fibers suppressed succinate-triggered oxygen consumption. Polyinosinic acid, a ligand of the scavenger receptor, inhibited the MMVF-induced decrease in ATP concentration. CONCLUSION: These results suggest that RF2 and RW1 can induce cytotoxicity and ATP depletion in the AM through the polyinosinic acid-inhibitable scavenger receptor. ATP depletion was the important factor in MMVF cytotoxicity, especially by RW1.

Adenosine Triphosphate↗
PubMed2001

Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ.

The 1H-NMR signal of the proximal histidyl-N(delta)H of deoxymyoglobin is detectable in the in situ rat myocardium and can reflect the intracellular PO2. Under basal normoxic conditions, the cellular PO2 is sufficient to saturate myoglobin (Mb). No proximal histidyl signal of Mb is detectable. On ligation of the left anterior descending coronary artery, the Mb signal at 78 parts/million (ppm) appears, along with a peak shoulder assigned to the corresponding signal of Hb. During dopamine infusion up to 80 microg. kg(-1) x min(-1), both the heart rate-pressure product (RPP) and myocardial oxygen consumption (MVO2) increase by about a factor of 2. Coronary flow increases by 84%, and O2 extraction (arteriovenous O2 difference) rises by 31%. Despite the increased respiration and work, no deoxymyoglobin signal is detected, implying that the intracellular O2 level still saturates MbO2, well above the PO2 at 50% saturation of Mb. The phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and the ratio of the change in P(i) over PCr (DeltaP(i)/PCr) increases by 0.19. Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a pyruvate dehydrogenase activator, abolishes the change in DeltaP(i)/PCr. Intracellular O2 supply does not limit MVO2, and the role of ADP in regulating respiration in rat myocardium in vivo remains an open question.

Adenosine Diphosphate↗
PubMed2000

Intactness of zona pellucida does not affect the secretion of a trypsin-like protease from mouse blastocyst.

Assisted hatching (AH), which is known to improve the hatching potential of mammalian embryos, has been used to increase the pregnancy rate in in vitro fertilization cycles. However, the effect of AH on a trypsin-like protease, which is known to be associated with the hatching process, has not been studied. In this study, we evaluate whether the intactness of zona pellucida affects the secretion of a trypsin-like protease from mouse blastocyst. Four- to 8-cell stage mouse embryos were collected at 66- to 68 hr after hCG injection and divided into 3 groups according to the manipulation of zona pellucida. The groups are no treatment (control), drilling of zona pellucida (ZD) and thinning of zona pellucida (ZT). The activity of a trypsin-like protease, blastocyst development and hatching rate were compared among the three groups at 110 and 135 hr after hCG injection, respectively. The protease activity and blastocyst development were not significantly different among control, ZD and ZT groups at 110 and 135 hr after hCG injection, respectively. However, the hatching rate of ZD and ZT groups was significantly higher than that of control group at each time, respectively (p<0.001). Even in the zona pellucida removed embryos, the protease activity did not differ from the control group. In conclusion, the secretion of a trypsin-like protease from mouse blastocyst does not seem to be affected by the intactness of zona pellucida.

Animals↗
PubMed1999

Mechanism of silica- and titanium dioxide-induced cytotoxicity in alveolar macrophages.

Particles can cause cytotoxicity in pulmonary alveolar macrophages (AM). Several mechanisms to explain this cytotoxicity have been suggested. However, the exact mechanism of particle-induced cytotoxicity in AM remains to be established. Silica and TiO2 produced a concentration-dependent cytotoxicity as evidenced by loss of cell viability and fall in ATP levels. While silica induced a greater cytotoxicity, TiO2 produced a higher reduction in ATP levels. Silica increased the release of LDH, but TiO2 did not affect enzymatic release. TiO2 suppressed succinate-triggered oxygen consumption, whereas silica did not markedly change the effect of succinate on oxygen consumption. Polyinosinic acid (PI), a ligand of the scavenger receptor, inhibited the TiO2-induced fall in ATP content, but could not prevent the effect of silica on cellular ATP content. Data suggest that silica and TiO2 can induce cytotoxicity in AM, probably through different mechanisms.

Adenosine Triphosphate↗
PubMed1999

Kinetic analysis of oral tolerance: memory lymphocytes are refractory to oral tolerance.

Oral administration of soluble Ag before immunization induces peripheral tolerance and is effective in suppressing animal models of autoimmune diseases. Although tolerance induction in primed animals is more clinically relevant, it is not well studied. Therefore, this study was designed to examine the feeding effects on different phases of the immune response. We observed that feeding a single high dose (250 mg) of OVA to OVA-primed BALB/c mice could induce OVA-specific suppression in the Ab production and T cell proliferation only at the naive and the activation phases of the immune response, whereas multiple high doses (100 mg/feed for 10 days) were effective at the effector phase. OVA-specific IL-4 production in culture supernatant was also suppressed in the tolerized groups. However, when the mice had resting memory lymphocytes, even multiple feeding regimens were not effective in tolerance induction, although multiple low doses (1 mg/feed for 10 days) partially suppressed Ab production. This phenomenon was confirmed by adoptive transfer study. Nevertheless, the reactivated memory response was suppressed partially by multiple high doses. Our findings have an important implication for understanding the mechanism of oral tolerance and for the therapeutic applications of oral tolerance to autoimmune diseases.

Administration, Oral↗
PubMed1999

Physicochemical characterization of YJA20379-8, a new proton pump inhibitor.

The physicochemical properties of the potent reversible proton pump inhibitor YJA20379-8, 3-butyryl-4-[(R)-1-methylbenzylamino]-8-ethoxy-1,7-naphthyridine, were studied. YJA20379-8 is essentially nonhygroscopic pale yellowish crystalline powder. It is practically insoluble in water, and its lipid solubility is high. The pH solubility profile exhibits an L-shaped curve, indicating YJA20379-8 is a basic substance having a soluble ionized form in acidic conditions. This is consistent with the result of an experiment to determine pKa. The solid-state stability study shows that YJA20379-8 is stable at various temperatures and humidities, but is decomposed by light.

Anti-Ulcer Agents↗
PubMed1999

A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors.

Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x3 subcutaneously with the specific Ras peptide along with Detox adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 micrograms). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy.

Adult↗
PubMed1999

Reconstruction of soft-tissue defects using serratus anterior adipofascial free flap.

The serratus anterior muscle has been suggested as a versatile and reliable flap for reconstruction of head and neck and extremity injuries. The adipofascial layer overlying the serratus anterior muscle is the anatomic layer, which is supplied by the same branch of thoracodorsal artery. Even though great progress has occurred in the prevention of postoperative adhesion of extremity injuries, the problem has not been completely solved and is still of special importance in complex injuries. Between March of 1995 and February of 1996, seven patients underwent reconstructive operation as a result of soft-tissue defects of the upper or lower extremities or the scalp. We transferred free adipofascial tissue overlying the serratus anterior muscle in three patients and both serratus anterior muscle and adipofascial tissue in four patients. A free adipofascial flap overlying serratus anterior muscle was transferred when a gliding surface was required, owing to the exposure of tendons and neurovascular structures. The average duration from operation to follow-up examination was 8 months (from 4 to 16 months). The results of the operations were satisfactory in functional and cosmetic aspects. This kind of flap was very effective in reconstruction of soft-tissue defects and gliding surfaces for these reasons: easy dissection, the capability of obtaining a long vascular pedicle, large-sized flap, composite flap including muscle or rib, and the fact that there was no serious functional or cosmetic deficit at the donor site.

Adult↗
PubMed1999

Regulation of respiration in myocardium in the transient and steady state.

1H/(31)P NMR has followed the metabolic response to increased work in the glucose- and pyruvate-perfused rat myocardium during a heart cycle and at the steady state. With electrical pacing and dobutamine, the heart O(2) consumption increases by 56%. The phosphocreatine (PCr) level initially declines, but recovers within 15 min to its control level; the oxymyoglobin (MbO(2)) saturation decreases by 15%. Because the MbO(2) signal reflects the intracellular PO(2), the capillary-to-cell O(2) gradient has increased to match the increased O(2) need. However, no transient metabolic fluctuation is observed in either PCr or MbO(2) throughout the entire cardiac cycle in both glucose and pyruvate-/glucose-perfused hearts. No systolic-diastolic variation is detectable under either high workload or hypoxic conditions. The results reveal that neither O(2) nor ADP is regulating respiration under increased energy demand in the steady or transient state.

Animals↗
PubMed1999

Comparative analysis of NMR and NIRS measurements of intracellular PO2 in human skeletal muscle.

1H NMR has detected both the deoxygenated proximal histidyl NdeltaH signals of myoglobin (deoxyMb) and deoxygenated Hb (deoxyHb) from human gastrocnemius muscle. Exercising the muscle or pressure cuffing the leg to reduce blood flow elicits the appearance of the deoxyMb signal, which increases in intensity as cellular PO2 decreases. The deoxyMb signal is detected with a 45-s time resolution and reaches a steady-state level within 5 min of pressure cuffing. Its desaturation kinetics match those observed in the near-infrared spectroscopy (NIRS) experiments, implying that the NIRS signals are actually monitoring Mb desaturation. That interpretation is consistent with the signal intensity and desaturation of the deoxyHb proximal histidyl NdeltaH signal from the beta-subunit at 73 parts per million. The experimental results establish the feasibility and methodology to observe the deoxyMb and Hb signals in skeletal muscle, help clarify the origin of the NIRS signal, and set a stage for continuing study of O2 regulation in skeletal muscle.

Adult↗
PubMed1999

Myoglobin desaturation with exercise intensity in human gastrocnemius muscle.

The present study evaluated whether intracellular partial pressure of O(2) (PO(2)) modulates the muscle O(2) uptake (VO(2)) as exercise intensity increased. Indirect calorimetry followed VO(2), whereas nuclear magnetic resonance (NMR) monitored the high-energy phosphate levels, intracellular pH, and intracellular PO(2) in the gastrocnemius muscle of four untrained subjects at rest, during plantar flexion exercise with a constant load at a repetition rate of 0.75, 0.92, and 1.17 Hz, and during postexercise recovery. VO(2) increased linearly with exercise intensity and peaked at 1.17 Hz (15. 1 +/- 0.37 watts), when the subjects could maintain the exercise for only 3 min. VO(2) reached a peak value of 13.0 +/- 1.59 ml O(2). min(-1). 100 ml leg volume(-1). The (31)P spectra indicated that phosphocreatine decreased to 32% of its resting value, whereas intracellular pH decreased linearly with power output, reaching 6.86. Muscle ATP concentration, however, remained constant throughout the exercise protocol. The (1)H NMR deoxymyoglobin signal, reflecting the cellular PO(2), decreased in proportion to increments in power output and VO(2). At the highest exercise intensity and peak VO(2), myoglobin was approximately 50% desaturated. These findings, taken together, suggest that the O(2) gradient from hemoglobin to the mitochondria can modulate the O(2) flux to meet the increased VO(2) in exercising muscle, but declining cellular PO(2) during enhanced mitochondrial respiration suggests that O(2) availability is not limiting VO(2) during exercise.

Adolescent↗