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Biomedical subjects

Y Hirayama

Publications and source records attributed to Y Hirayama.

At least 37 records · Page 2Linked to original sources
PubMed2002

Phase diagram of interacting composite fermions in the bilayer nu=2/3 quantum hall effect.

We study the phase diagram of composite fermions (CFs) in the presence of spin and pseudospin degrees of freedom in the bilayer nu=2/3 quantum Hall (QH) state. Activation studies elucidate the existence of three different QH states with two different types of hysteresis in the magnetotransport. While a noninteracting CF model provides a qualitative account of the phase diagram, the observed renormalization of tunneling gap and a non-QH state at high densities are not explained in the noninteracting CF model, and are suggested to be manifestations of interactions between CFs.

Journal Article↗
PubMed2002

Nonequilibrium transport through a vertical quantum dot in the absence of spin-flip energy relaxation.

We investigate nonequilibrium transport in the absence of spin-flip energy relaxation in a few-electron quantum dot artificial atom. Novel nonequilibrium tunneling processes involving high-spin states, which cannot be excited from the ground state because of spin blockade, and other processes involving more than two charge states are observed. These processes cannot be explained by orthodox Coulomb blockade theory. The absence of effective spin relaxation induces considerable fluctuation of the spin, charge, and total energy of the quantum dot. Although these features are revealed clearly by pulse excitation measurements, they are also observed in conventional dc current characteristics of quantum dots.

Journal Article↗
PubMed2002

Electrically controlled nuclear spin polarization and relaxation by quantum-Hall states.

We study interactions between electrons and nuclear spins by using the resistance ( Rxx) peak which develops near the Landau-level filling factor nu = 2/3 as a probe. Temporarily tuning nu to a different value, nu(temp), with a gate demonstrates that the Rxx peak regenerates even after complete depletion ( nu(temp) = 0), while it rapidly relaxes on either side of nu(temp) = 1. This indicates that the nu = 2/3 domain morphology is memorized by the nuclear spins which can be rapidly depolarized by Skyrmions. An additional enhancement in the nuclear spin relaxation around nu = 1/2 and 3/2 suggests a Fermi sea of partially polarized composite fermions.

Journal Article↗
PubMed2002

Hypothalamic growth hormone deficiency and supplementary GH therapy in two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes.

Two pediatric patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes were diagnosed with growth hormone deficiency with the primary lesion identified as the growth hormone-releasing factor producing cells of the hypothalamus. Stimulation tests with insulin, levodopa and sleep did not overcome the deficient pattern of growth hormone secretion. By comparison, the growth hormone-releasing factor stimulation test generated a normal growth hormone response in these two patients. Growth hormone supplementary therapy was effective in terms of growth gain without adverse effects.

Child↗
PubMed2001

Local density of states in zero-dimensional semiconductor structures.

The local density of states (LDOS) within tetrahedral InAs structures, formed at the surface of InAs/GaAs(111)A, has been characterized using low-temperature scanning tunneling microscopy. The LDOS of the lowest four zero-dimensional (0D) discrete levels have been imaged in structures with a comparable size to the electron wavelength. The LDOS inside the structures is observed to be higher than that of the surrounding area at intervals of the level separation. This feature indicates the singularity of the LDOS close to the 0D resonant levels.

Journal Article↗
PubMed2001

Charge excitations in easy-axis and easy-plane quantum Hall ferromagnets.

We study charge excitations in quantum Hall ferromagnets realized in a symmetric quantum well. Landau levels (LLs) with different subband and orbital indices crossing at the Fermi level act as up and down pseudospin levels. The activation energy measured as a function of the pseudospin Zeeman energy, Delta(Z), reveals easy-plane and easy-axis ferromagnetism for LL filling of nu = 3 and 4, respectively, for which the crossing levels have parallel and antiparallel spin. For nu = 4, we observe a sharp reduction in the gap for Delta(Z)-->0, which we discuss in terms of a topological excitation in domain walls akin to Skyrmions.

Journal Article↗
PubMed2001

Anthraquinon-2-ylmethoxycarbonyl (Aqmoc): a new photochemically removable protecting group for alcohols.

[see structure]. Synthesis and photochemistry of a new photochemically removable protecting group for alcohols is described. Four carbonates of galactose derivatives (1-4) were synthesized from the corresponding arylmethanols via 4-nitrophenyl carbonate intermediates. Among them, photolysis of anthraquinon-2-ylmethoxycarbonyl (Aqmoc) galactose (1) proceeded with overall photolysis efficiency of 150 (quantum yield 0.10, and molar absorptivity 1500 M(-1) x cm(-1)) and rate constant of approximately 10(6) s(-1). To demonstrate its application to a biologically related molecule, 5'-Aqmoc-adenosine (5) was synthesized and photolyzed to yield adenosine in 91% yield.

Journal Article↗
PubMed2001

Imaging of Friedel oscillation patterns of two-dimensionally accumulated electrons at epitaxially grown InAs(111) A surfaces.

The local density of states (LDOS) at the epitaxially grown InAs surface on a GaAs(111) A substrate were characterized using low-temperature scanning tunneling microscopy. Using dI/dV signal mapping, LDOS standing waves were clearly imaged at point defects and within nanostructures. Measurement of the wavelength as a function of bias voltage showed a nonparabolic dispersion relation for the conduction band. The observed wave features originate from the Friedel oscillations of the two-dimensional electron gas in the semiconductor surface accumulation layer.

Journal Article↗
PubMed2001

Single nucleotide instability without microsatellite instability in rat mammary carcinomas.

Mutation frequencies (MnFs) of the lacI transgene and mutation rates (MRs) of the endogenous hprt gene were analyzed in two mammary carcinoma cell lines that we established from mammary carcinomas that had been induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in female lacI-transgenic rats. Using the lacI transgene, corrected MnF, which is the number of independent lacI mutations that occurred while 102 cells expanded into 10(7) cells and which reflect the dynamic increase of point mutations, was measured. The corrected MnFs in the two mammary carcinoma cell lines (59 x 10(-6) and 72 x 10(-6) mutations) were significantly higher than that in the primary culture of normal mammary epithelium (4.7 x 10(-6)). MRs of the hprt gene in the two mammary carcinoma cell lines (8.2 x 10(-7) and 11 x 10(-7) mutations/hprt/cell division) were also higher than the same control (1.4 x 10(-7)). A:T to C:G transversion was observed at significantly higher frequencies in the two cell lines (6 of 24 and 6 of 25 for lacI; 10 of 67 and 19 of 92 for hprt) than in the control (0 of 6 for lacI; 0 of 4 for hprt). Taking advantage of the lacI transgene, high frequencies of A:T to C:G transversion (6 of 38 and 8 of 33, respectively) was also confirmed in the primary carcinomas of the two cell lines, which indicated the presence of a common abnormality in the cell lines and in the primary carcinomas. Both the established cell lines and their primary carcinomas were negative for microsatellite instability, which is known to be caused mainly by mismatch repair insufficiency and to increase point mutations, and for p53 mutations. These findings showed that the two cell lines, and possibly their primary carcinomas, had increases in the MRs of point mutations attributable to a mechanism(s) different from mismatch repair insufficiency, and we would suggest that such a state be designated as single nucleotide instability (SNI).

Animals↗
PubMed2001

Prevention of lethal acute graft-versus-host disease in mice by oral administration of T helper 1 inhibitor, TAK-603.

Acute graft-versus-host diseases (GVHD) is a major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). T helper 1 (Th1)-type cytokines such as interferon-gamma or tumor necrosis factor-alpha have been implicated in the pathogenesis of acute GVHD. TAK-603 is a new quinoline derivative, which is now in clinical trials for use as a disease-modifying antirheumatic drug. In preclinical studies, it inhibited delayed-type hypersensitivity, but not Arthus-type reaction, in mice, and selectively suppressed Th1 cytokine production. Thus, the present study was designed to investigate whether the Th1 inhibitor (TAK-603) ameliorates lethal acute GVHD in a mouse model. Administration of TAK-603 into BALB/c mice given 10 Gy total body irradiation followed by transplantation of bone marrow and spleen cells from C57BL/6 mice markedly reduced the mortality in association with minimal signs of GVHD pathology in the liver, intestine, and skin. TAK-603 reduced not only the production of Th1-type cytokines, but also the proportion of Th1 cells in CD4(+) helper T cells in this GVHD mouse model. These results suggest that TAK-603 could be a potent therapeutic agent for acute lethal GVHD.

Acute Disease↗
PubMed2001

Long-term survival and late-onset complications of cancer patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation.

The antitumor effect of high-dose chemotherapy (HDC) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered superior to that of conventional chemotherapy. However, the long-term benefits of this strategy in Japan remain unclear. Therefore, in this study, 109 cancer patients enrolled between 1989 and 1999 were treated with HDC and auto-PBSCT. Patients were evaluated for long-term survival and late-onset complications, including secondary malignancy. The mean number of CD34+ cells harvested per apheresis was larger in the group receiving high-dose cytosine arabinoside or high-dose etoposide plus granulocyte colony-stimulating factor (G-CSF) than in the group receiving conventional chemotherapy plus G-CSF. The 5-year overall survival rates for non-Hodgkin's lymphoma patients in first complete remission (CR) (83.2%), second or subsequent CR (74.1%), or first partial remission (PR) (66.7%) at the time of transplantation were significantly higher than those with no remission (35.7%) at the time of transplantation (first CR, P < .05; second or subsequent CR, P < .05; first PR, P < .05). The 5-year overall survival (OS) rates for breast cancer was 40.8%, and the disease-free survival rate was extremely low (8.8%). The 5-year OS rates for chemotherapy-sensitive and chemotherapy-resistant diseases at the time of transplantation were 32.7% and 35.7%, respectively, a difference that was not considered significant. The 5-year OS for germ cell tumor was 80.0%, and the disease-free survival rate was 77.9%. The rate of therapy-related death was 8.2%. The occurrence rate of secondary malignancy was 0.9%. Late-onset complications were observed in 4 cases (glomerulonephritis, interstitial pneumonitis, ulcerative colitis, and acute myelogenous leukemia). At 3.7%, the occurrence rate was not very high, but most complications of auto-PBSCT were life threatening and interfered with patients' quality of life. A careful follow-up is required for at least 2 years after transplantation, because the mean occurrence time of late-onset complications is 16.7 months posttransplantation.

Adult↗
PubMed2001

Meningeal carcinomatosis from an ovarian primary with complete response to adjuvant chemotherapy after cranial irradiation.

Meningeal metastasis is rare in the clinical course of ovarian carcinoma, and its prognosis is poor. Meningeal dissemination of carcinoma is usually treated by intrathecal administration of methotrexate and total brain irradiation, although these treatments are usually ineffective. We experienced a case of meningeal relapse from ovarian carcinoma resistant to multiple antineoplastic agents in a 64-year-old woman who was treated with eight different chemotherapy regimens after her initial operation 7 years previously. Intrathecal administrations of methotrexate or cisplatin with dexamethasone were not effective. Fifty-Gy whole cranial irradiation inhibited increases in serum carbohydrate antigen (CA) 125 levels and further tumor growth. Adjuvant chemotherapy was required to alleviate frequent headaches and to decrease serum CA125 level and tumor size. Intravenous administration of 45 mg paclitaxel and 35 mg cisplatin, and oral administration of 50 mg etoposide were carried out for 5 days. This treatment was repeated every 3 weeks. After four courses of treatment, meningeal carcinomatosis was not detectable on computed tomography (CT) and magnetic resonance imaging (MRI) scans. The patient's serum levels of CA125 rapidly fell to beneath normal limits and remained normal. She is still alive and clinically free of recurrence 4 months after the last cycle of chemotherapy. As well as reporting our experience with this case, we also present a review of the literature on meningeal carcinomatosis from ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis.

Tuberous sclerosis complex (TSC) is a multisystemic disorder characterized by systemic hamartomas. Although the disease-determining genes TSC1 and TSC2 have been isolated, the molecular pathogenesis of the disease is not understood. We examined cell cycle abnormalities in skin specimens and cultured cells derived from specific lesions of TSC patients with confirmed TSC1 or TSC2 mutations. None of the specimens used in this study showed loss of heterozygosity (LOH). We detected more cells positive for PCNA and fewer cells positive for MPP2 in the epidermis of TSC patients than in the epidermis of control patients without TSC. Incorporation of 5-bromo-2-deoxyuridine (BrdU) was similar in fibroblasts derived from TSC lesions and in normal human fibroblasts. These results suggest that the cell cycle of TSC cells shows a prolonged S phase. Flow cytometric analysis confirmed S phase prolongation in TSC cells. Many apoptotic cells were detected by a nick end labeling assay in both skin tissue and cultured fibroblasts derived from specific TSC lesions. Examination of cyclin levels showed increased nuclear cyclin A and cytoplasmic cyclin B and decreased nuclear cdc2 levels. We conclude that suppression of either TSC1 or TSC2 may change cyclin levels, prolong S phase and induce apoptotic cell death.

Adult↗
PubMed2001

Atopic dermatitis-like skin lesions induced by topical application of mite antigens in NC/Nga mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammation usually observed in patients with an individual or a familial history of atopic diseases, precipitated by environmental factors including mite antigens (Ag). However, the exact etiology of AD is unclear. To further explore the pathogenesis and treatment of AD, a suitable animal model is necessary. In this study, we developed a new animal model of AD induced by mite Ag in NC/Nga mice. METHODS: We injected the extracts of mite Ag intradermally at the ventral side of the ear of SPF NC/Nga mice on days 0, 2, 4, 7, 9, 11, 14 and 16, and measured the clinical symptoms and the ear thickness. On day 18, we collected blood and submandibular lymph nodes (LN) of the immunized ear to perform a histochemical analysis, and to measure the plasma immunoglobulins and cytokines. RESULTS: The NC/Nga mice immunized with mite Ag suffered from AD-like skin lesions including erythema followed by edema, excoriation and scaling. The histological and immunohistochemical examinations of the affected skin showed epidermal hyperplasia with hyperkeratosis, severe infiltration of CD4+ T lymphocytes, eosinophils and macrophages, and degranulation of mast cells. The total plasma IgE level was markedly elevated in mite Ag-treated mice. LN cells of mice immunized with mite Ag synthesized IgE in an Ag-dependent manner and secreted interleukin-4 (IL-4) and IL-5 but not interferon-gamma. CONCLUSIONS: NC/Nga mice treated with mite Ag manifest clinical and immunological aspects similar to patients with AD, suggesting that this model is suitable for exploring the pathogenesis of human AD.

Allergens↗
PubMed2001

Beat dependent alteration of Ca2+-activated Cl- current during rapid stimulation in rabbit ventricular myocytes.

The transient outward currents (Ito) play an important role in action potential repolarization in cardiac myocytes. Two components of Ito have been identified as 4-AP-sensitive but Ca2+-insensitive Ito carried by K, and Ca2+-sensitive but 4-AP insensitive Ito carried by Cl- (I(Cl(Ca))). It is known that the amplitudes of Ito change depending on the stimulation frequency. In this study we investigated the beat dependent alteration of I(Cl(Ca)) during rapid stimulation using the whole cell patch clamp technique in rabbit ventricular myocytes. The cells were internally perfused with a solution containing 0.1 microM free Ca2+ to develop I(Cl(Ca)) and all internal K+ was replaced with Cs+ to block 4-AP-sensitive Ito and other K+ currents. By applying depolarizing pulses at a high frequency of 2.5 Hz, the amplitudes of I(Cl(Ca)) gradually increased as the number of pulses increased following a transient decrease in the 2nd pulse and reached a plateau level at the 20th pulse. The shape of the current-voltage curve of I(Cl(Ca)) was not overly different for different numbers of preceding pulses. The recovery from inactivation of I(Cl(Ca)) could be fitted to a single exponential curve and full recovery was achieved after > 1 sec with a time constant of 368 ms. The ramp clamp experiments showed that the conductance of the background I(Cl(Ca)) increased with the preceding pulse numbers, indicating that the resting level of [Ca2]i increased with the pulses applied. From these results, we conclude that beat dependent alteration of I(Cl(Ca)) is determined by not only its apparent kinetic property, but also the resting level of [Ca2+]i during rapid stimulation.

Action Potentials↗
PubMed2001

Successful treatment of a case of relapsed acute promyelocytic leukemia with arsenic trioxide.

We report a patient with an initial relapse of acute promyelocytic leukemia (APL) who achieved a second complete remission (CR) after treatment with arsenic trioxide. The patient, a 66-year-old woman diagnosed as having relapsed APL, received arsenic trioxide intravenously at a dose of 10 mg/day. At day 36, the patient achieved a second CR. The side effects were slight neuralgia and mild skin erythematous changes, which improved following cessation of the drug. Although arsenic trioxide may be effective for relapsed APL, it should be used with caution because of various complications.

Aged↗