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Biomedical subjects

M Aoyagi

Publications and source records attributed to M Aoyagi.

At least 109 records · Page 6Linked to original sources

[Complete remission achieved by low-dose Ara-C, aclarubicin and rhG-CSF (CAG) therapy in acute non-lymphocytic leukemia with monosomy 7 occurring after severe aplastic anemia].

We report a case of acute myelogenous leukemia (AML), which developed from severe aplastic anemia (SAA) and was successfully treated by low-dose Ara-C and aclarubicin with concomitant use of G-CSF (CAG therapy). A 37-year-old male was admitted for scrutiny of pancytopenia and diagnosed as SAA because of hypocellular bone marrow without abnormal or dysplastic cells. Although hematopoiesis recovered with steroid pulse therapy followed by administration of anabolic steroids, 29 months after initial onset of SAA, he presented as AML (FAB-M6), as his bone marrow Contained 21.6% leukemic myeloblasts and 56% of erythroblasts. Chromosome study revealed 45, XY, -7 in 14 of 20 cells analyzed. Complete remission was achieved by administration of low-dose Ara-C (20 mg/m2 for 7 days) and aclarubicin (14 mg/m2 for 4 days) along with G-CSF (200 micrograms/m2 for 7 days), without any severe complications. In the previous reports in Japan since 1982, 7 out of 8 cases with AML developing from SAA died within a year. Our results indicate that CAG therapy is useful for treatment for this subset of AML with poor prognosis.

Aclarubicin↗

Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to secrete interleukin 2.

Adoptive immunogene therapy of cancer is not widely studied, although it has been proposed as a promising strategy for cancer gene therapy. One of the major obstacles to this approach is the difficulty in introducing cytokine genes efficiently into T lymphocytes. In this report, we developed an adoptive immunotherapy model with murine tumor-specific cytotoxic T lymphocytes. By using an adenoviral vector, we achieved up to 100% gene transduction of murine T lymphocytes. Treatment of mice with the cytotoxic T lymphocytes genetically modified to produce interleukin 2 resulted in reduction of tumor metastasis and longer survival from intracerebral tumor death, providing a hopeful strategy for treatments of human cancers.

Adenoviridae↗

IL-5 mRNA expression in blood lymphocytes from patients with Kimura's disease and parasite infection.

Blood lymphocytes from patients with eosinophilia are known to produce interleukin-5 (IL-5) with appropriate stimulation in vitro. To determine whether blood lymphocytes from these patients produce IL-5 in vivo, we tested the IL-5 mRNA expression in blood lymphocytes immediately after separation by reverse-transcriptase polymerase chain reaction (RT-PCR) method. We found that lymphocytes from eosinophilic patients expressed IL-5 mRNA, but lymphocytes from normal volunteers did not express the lymphokine. These findings suggest that in patients with eosinophilia, peripheral blood lymphocytes produce IL-5 in vivo.

Adult↗

Effect of endothelin-1 as growth factor on a human glioma cell line; its characteristic promotion of DNA synthesis.

In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) has been recognized to stimulate DNA synthesis in some cell lines. In this study, we confirmed the existence of ET-1 receptor in YKG-1 human glioma cells, and investigated its effect on DNA synthesis in YKG-1 for 6 consecutive days, comparing it with that of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Scatchard analysis of the binding data revealed the presence of a single class of high-affinity binding molecule. The apparent dissociation constant (Kd) was 5.2 x 10(-9) M and the maximal binding capacity (B max) was 4.7 x 10(4) sites/cell. The percentage of non-cycling cells was initially more than 85%, and decreased to 55.40%, 24.22%, 11.50%, and 7.51% on days 1, 2, 4, and 6, respectively, after ET-1 stimulation. Although ET-1 reduces the fraction of non-cycling cells more slowly than other growth factors such as EGF, PDGF and IGF-I, it reaches the same level as the others by day 6. These results indicate that YKG-1 human glioma cells have ET-1 receptors and that ET-1 initiates a peculiar slow induction of DNA synthesis in these cells, suggesting that secondary factors might exist to accelerate the DNA synthesis in response to ET-1.

Cell Cycle↗

Effects of acoustic overstimulation on cochlear evoked potentials.

Guinea pigs were exposed to 2 kHz pure-tone or octave-band pass noise at an intensity of 100 dBSPL for 30 min. The effects of sound exposure on cochlear microphonics (CM) and compound action potential (AP) were studied using a test condition devised to complete the measurement of the sensitivity of both potentials for the frequency from 1 to 7 kHz within several minutes. The loss of CM sensitivity was limited to around 5 dB for all test frequencies in animals exposed either to pure-tone or band noise. In contrast, the loss of AP in both exposure conditions was significantly greater than that of the CM, and the magnitude of the AP losses reflected the frequency characteristics of the exposure sounds. From these observations, the AP is considered to be a more sufficient index than the CM in studying the effects of acoustic overstimulation.

Animals↗

Human arterial smooth muscle cell strains derived from patients with moyamoya disease: changes in biological characteristics and proliferative response during cellular aging in vitro.

Moyamoya disease is a progressive cerebrovascular occlusive disease that occurs frequently in children. The etiology is unknown. We examined changes in biological characteristics and responsiveness to serum mitogens during the in vitro cellular aging of arterial smooth muscle cell strains derived from patients with moyamoya disease (HMSMC) and compared them with those of cells from age-matched control patients (HCSMC). HMSMC had a normal human diploid chromosome constitution. HMSMC and HCSMC had almost the same in vitro life span and the age-related patterns of biological parameters were essentially the same. However, the doubling time at the early passages was significantly longer in moyamoya SMC than control SMC, although there was no significant difference at the late passages. Furthermore, the poor responsiveness of moyamoya SMC to platelet-derived growth factor was retained throughout the life span in vitro. These results support the hypothesis that functional alterations in vascular cells are involved in the mechanism of development of intimal thickening in moyamoya disease.

Adolescent↗

Suppression of normal hematopoiesis in acute leukemia: effect of leukemic cells on bone marrow stromal cells and hematopoietic progenitor cells.

Effects of leukemic cells (LC) on bone marrow stromal cells and myeloid progenitor cells (CFU-C) were studied in vitro, using LC lines with different lineage characteristics. LC and/or LC-conditioned medium (LC-CM) inhibited the growth of a stromal cell line, KM-101, and adherent cells of a long-term bone marrow culture (LTBMC) established from normal bone marrow. The inhibition was more prominent when LC were cocultured directly with KM-101 cells than when LC were cultured separate from the KM-101 cell layer via membrane filtration, or when LC-CM was added to KM-101 cells or LTBMC. LC-CM also exerted an inhibitory effect on the ability of LTBMC adherent cells to bind CFU-C. Furthermore, LC-CM inhibited the growth and survival of early and late CFU-C, but not the growth of LC. All these inhibitory effects were seen irrespective of the lineage characteristics of LC, but not seen with CM prepared from normal bone marrow immature granulocytes or peripheral blood lymphocytes. Neither tumor necrosis factor-alpha nor interferon-alpha was detected in these LC-CM. These findings suggest that LC suppress normal hematopoiesis through the release of undefined substance(s) inhibiting the growth and/or survival of stromal cells and hemopoietic progenitor cells as well as the function of stromal cells.

Bone Marrow↗

Pure-tone threshold prediction by 80-Hz amplitude-modulation following response.

The usefulness of 80-Hz amplitude-modulation following response (AMFR) detected by phase spectral analysis to predict the hearing threshold during sleep was evaluated in 20 normal adults, 8 normal children and 37 children with hearing impairment. The onset effect of tonal stimulus on 80-Hz steady state response was studied in normal adults during sleep and a threshold of 80-Hz AMFR detected by phase spectral analysis was compared with that of ABR elicited by tone pips in children during sleep. Although 80-Hz AMFR is not appropriate for the assessment of hearing in adults, it appears useful for evaluating hearing in young children during sleep. Hearing prediction by 80-Hz AMFR appears to be more accurate than that by ABR elicited with tone pips. The onset effect of stimulus on 80-Hz AMFR with modulation depth of 95% was less than 80-Hz SSR evoked by clicks.

Acoustic Stimulation↗

Effects of aging on amplitude-modulation following response.

Phase spectral analysis as developed by Fridman (1982) was used to detect amplitude-modulation following response (AMFR). The threshold of AMFR was determined with greater sensitivity and accuracy by phase spectral analysis than by visual analysis. Using this method, a modulation frequency (MF) of 80 Hz was found optimal for detecting AMFR in young children (ranging in age from 2 to 4 years) during sleep, for whom there is no advantage in recording 40-Hz steady-state responses. To determine the optimal MF for detecting AMFR during sleep in children less than 2 years of age and age limitation for using 80-Hz MAFR in objective audiometry, AMFR as a function of MF was investigated during sleep in 25 children with normal hearing ranging from 4 months to 15 years of age, and 10 normal hearing adults. The stimulus was a 1000 Hz, 50 dBnHL sinusoidally amplitude modulated tone with a modulation depth of 95%. MF was varied from 20 to 200 Hz in 20 Hz steps. Response was determined by phase spectral analysis and the S/N ratio calculated by spectral amplitude at the modulation frequency and noise level around the modulation frequency using fast Fourier transform. Phase spectral analysis showed AMFR at MF of 80 Hz to be the most stable and reliable in all children during sleep among MFs from 20 to 200 Hz. Spectral amplitude analysis demonstrated 80-Hz AMFR to have a high S/N ratio in all children.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Detectability of amplitude-modulation following response at different carrier frequencies.

To assess the detectability of amplitude-modulation following response (AMFR) elicited at different carrier (CFs) and modulation frequencies (MFs) during sleep, as well as the usefulness of AMFR in evoked response audiometry, AMFR was examined in 10 adults with normal hearing while sleeping. The stimulus was a 50 dBnHL sinusoidally amplitude-modulated (SAM) tone with a modulation depth of 95%. The MF of the stimulus tone was varied from 20 to 120 Hz in 20 Hz steps and CFs were 500, 1000, 2000 and 4000 Hz. An SAM tone with a CF of 20,000 Hz was used for stimulation in 5 subjects to confirm that the response did not contain any artifact. Response was determined by phase spectral analysis. The component synchrony measure of AMFRs at MF of 40 Hz (40-Hz AMFR) was high at lower CFs, but 40-Hz AMFRs at higher CFs were unreliable. The detectability of 80-Hz AMFR was high for all CFs. It was confirmed that the response waveform was not contaminated by any electromagnetic artifact. Eighty-Hz AMFR detected by phase spectral analysis should thus be useful for predicting frequency-specific hearing thresholds during sleep.

Acoustic Stimulation↗

A study on the phase spectral analysis of middle latency response and 40-Hz event-related potential in central nervous system disorders.

The synchrony measure method, or SM method, a phase spectral analysis described by Fridman in 1984 for ABR, was applied to 40-Hz event-related potential (40-Hz ERP), and was found to be a useful method for automatic detection in predicting hearing thresholds across the audiometric frequencies. Although 40-Hz ERP was claimed by Galambos to be the summation of middle latency responses (MLR), its origin is still controversial. Moreover, only a few articles have reported on the clinical use of 40-Hz ERP in patients with neurological disorders. We recorded ABRs, MLRs, and 40-Hz ERPs in 59 patients with central nervous system (CNS) disorders, and analyzed the relationship between central lesions and MLR or 40-Hz ERP using phase spectral analysis. Abnormal findings in 40-Hz ERP were observed in 43 (72.9%) out of 59 cases with CNS disorders, and most of the abnormal cases had disorders involving the midbrain or thalamic lesions, especially on the side contralateral to stimuli. The results suggest that phase spectral analysis of 40-Hz ERP is useful in the detection of CNS disorders.

Acoustic Stimulation↗

Hearing preservation and improvement of auditory brainstem response findings after acoustic neuroma surgery.

Among 9 patients with acoustic neuroma who underwent tumor removal by the middle cranial fossa approach during the past 5 years, 6 were selected for hearing preservation surgery which was successful in 5 cases (83.3%). For the prediction of success in hearing-preservation, factors related to hearing preservation, including preoperative findings of neurotological examination, were analyzed. Postoperative hearing threshold correlated significantly with wave V latency and I-V interpeak latency of preoperative auditory brainstem response (ABR) and the SP/AP ratio of preoperative electrocochleogram and postoperative facial palsy. The size of tumors and preoperative results of speech audiometry did not correlate with hearing results. Postoperative ABR findings were normalized within the observation period from 5 days to 10 months in 3 hearing-preserved patients. Possible mechanisms for improvement of ABR findings after the removal of acoustic neuroma are discussed.

Adult↗