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Biomedical subjects

Y Hayakawa

Publications and source records attributed to Y Hayakawa.

At least 55 records · Page 3Linked to original sources

Ammocidin, a new apoptosis inducer in Ras-dependent cells from Saccharothrix sp. I. Production, isolation and biological activity.

A new apoptosis inducer, ammocidin, was isolated from the culture broth of Saccharothrix sp. AJ9571. Ammocidin induced apoptotic cell death in Ras-dependent Ba/F3-V12 cells with an IC50 of 66 ng/ml. No cell death was observed in IL-3-dependent Ba/F3-V12 cells at less than 100 microg/ml of ammocidin. Ammocidin significantly reduced the phosphorylation level of MAPK and S6K that mediate the anti-apoptotic function of Ras.

Actinomycetales↗

Multifocal electroretinograms in patients with branch retinal artery occlusion.

PURPOSE: To investigate the usefulness of second-order multifocal electroretinograms (MERGs) for detecting inner retinal disorders. METHODS: The MERG from 5 patients with branch retinal artery occlusion (BRAO) was recorded. Twelve eyes of 12 normal subjects were also tested. MERGs were recorded using 61 hexagons. Bright flash ERGs were also recorded to measure the oscillatory potentials (OP). Root mean square (RMS) measures of the local first- and second-order MERGs (fMERG and sMERG) were compared in the affected and unaffected areas. The first negative trough (N1) and first positive peak (P1) were also used for measuring the amplitudes and latencies of the fMERG. RESULTS: The fMERG RMS-amplitudes decreased significantly (r = 0.56, P: < 0.05) in the affected area compared with normal values. The fMERG latencies of N1 and P1 increased significantly (P: < 0.05) in the affected area. Furthermore, the sMERG RMS-amplitudes decreased almost to the noise level (r = 0.28, P: < 0.001) in the affected areas. The interocular ratio of the sMERG RMS-amplitudes (affected/normal) significantly correlated with that of the fMERG (r = 0.69, P: < 0.001). The fMERG latencies significantly correlated with the sMERG RMS-amplitude (r = 0.37 approximately 0.69, P: < 0.05 approximately 0.001), but only began to increase after a 30% to 50% loss of the sMERG amplitude. The summed OP amplitude decreased to the same extent as the sMERG in the affected eye (0.5 of the normal eye). CONCLUSIONS: Although the fMERG amplitude and latency were significantly changed, the sMERG was much more affected by BRAO. The marked reduction of the sMERG in the affected area strongly suggested its main source was from the more inner layers of the retina compared to the fMERG. The sMERG appeared to be a sensitive indicator of inner retinal dysfunction.

Adolescent↗

Cross-axis adaptation of pursuit initiation in humans.

PURPOSE: The initial acceleration of pursuit in the open-loop period is under adaptive control and undergoes motor learning. The current study was undertaken to examine the hypothesis that the direction of pursuit initiation can also be adaptively modified. METHODS: Four neurologically and ophthalmologically normal subjects participated in the experiment. A modified step-ramp paradigm was used to induce cross-axis adaptation, in which a ramp target changed its direction orthogonally just after the target crossed the center. Four direction changes were tested in separate experiments: left to up, left to down, down to left, and up to left. During a 30-minute adaptation session, the target moved in one of two randomly chosen directions (right to left or up to down) at one of two randomly chosen speeds (15.6 or 22.3 deg/sec), but the target changed orthogonally in only one direction. A linear regression fit to the initial 100-msec segment of the pursuit trace was used to determine the direction of pursuit initiation. RESULTS: In all cases, an adaptive change in pursuit initiation was gradually induced in the direction called for by the training paradigm. Adaptation was usually completed (90 degrees shift) within the 30-minute training session but declined quickly to an approximate 30 degrees -shift after training. The latency and vectorial amplitude of the initial acceleration remained unchanged. The adaptation was specific for the direction but not the velocity of the target. CONCLUSIONS: This study showed that the direction of pursuit initiation is under adaptive control, as has been shown for saccadic eye movements and the vestibulo-ocular reflex.

Adaptation, Ocular↗

[Finding appropriate endotracheal tube position by Trachlight in children].

Finding appropriate endotracheal tube position in children is important, because the trachea length of a child is shorter than that of an adult, and the position of the endotracheal tube is easy to be altered by head position, rotary movements, and flexion as well as extension. We confirmed the correct depth of the endotracheal tube by transillumination method using the Trachlight device in children. Twenty children were intubated orally with a rigid laryngoscope according to the distance of the formula height/10 + 5 cm at the lips. We measured the distance from the tip of the tube to the sternal notch where the bright light of the Trachlight disappeared. The tip of the endotracheal tube (4.5, 5.0 or 5.5 mm tube size) was placed approximately 1.5 cm beyond the sternal notch. The distance between the carina and the tube tip measured by chest radiography was more than 1 cm. Trachlight device was simple and reliable to ensure the appropriate endotracheal tube position in children. We consider that the appropriate depth of the endotracheal tube using any of 4.5, 5.0 or 5.5 mm tube size is 1.5 cm beyond the point the bright light of the Trachlight disappears.

Anesthesia, General↗

Discovery of a novel antitumor benzolactone enamide class that selectively inhibits mammalian vacuolar-type (H+)-atpases.

A series of naturally occurring compounds reported recently by multiple laboratories defines a new small-molecule class sharing a unique benzolactone enamide core structure and diverse biological actions, including inhibition of growth of tumor cells and oncogene-transformed cell lines. Here we show that representative members of this class, including salicylihalamide A, lobatamides A-F, and oximidines I and II inhibit mammalian vacuolar-type (H+)-ATPases (V-ATPases) with unprecedented selectivity. Data derived from the NCI 60-cell antitumor screen critically predicted the V-ATPase molecular target, while specific biochemical assays provided confirmation and further illumination. The compounds potently blocked representative V-ATPases from human kidney, liver, and osteoclastic giant-cell tumor of bone but were essentially inactive against V-ATPases of Neurospora crassa and Saccharomyces cerevisiae and other membrane ATPases. Essential regulation of pH in cytoplasmic, intraorganellar, and local extracellular spaces is provided by V-ATPases, which are ubiquitously distributed among eukaryotic cells and tissues. The most potent and selective V-ATPase inhibitors heretofore known were the bafilomycins and concanamycins, which do not discriminate between mammalian and nonmammalian V-ATPases. Numerous physiological processes are mediated by V-ATPases, and aberrant V-ATPase functions are implicated in many different human diseases. Previous efforts to develop therapeutic pharmacological modulators of V-ATPases have been frustrated by a lack of synthetically tractable and biologically selective leads. Therefore, availability of the unique benzolactone enamide inhibitor class may enable further elucidation of functional and architectural features of mammalian versus nonmammalian V-ATPase isoforms and provide new opportunities for targeting V-ATPase-mediated processes implicated in diverse pathophysiological phenomena, including cancer.

Animals↗

Critical contribution of IFN-gamma and NK cells, but not perforin-mediated cytotoxicity, to anti-metastatic effect of alpha-galactosylceramide.

The glycolipid alpha -galactosylceramide (alpha -GalCer), which is presented by CD1d and specifically activates Valpha 14 NKT cells, exerts a potent anti-metastatic effect when administered in vivo. In this study, we demonstrated that alpha -GalCer administration led to rapid elimination of NKT cells by apoptosis in the liver and spleen, after they produced IFN-gamma and IL-4. In contrast, a more prolonged secretion of IFN-gamma was observed by liver and splenic NK cells after alpha -GalCer administration. Cytotoxic activity of liver mononuclear cells was not augmented 3h after alpha -GalCer administration, but was increased at 24 h when NKT cells were mostly depleted. The alpha -GalCer-induced cytotoxic activity was abolished in IFN-gamma -deficient and NK cell-depleted mice as well as CD1-deficient mice, suggesting that the alpha -Galcer-induced cytotoxicity was mainly mediated by IFN-gamma -activated NK cells. While the alpha -GalCer-induced cytotoxicity in vitro was mostly perforin dependent, anti-metastatic effect of alpha -GalCer was impaired in NK cell-depleted or IFN-gamma -deficient mice but not in perforin-deficient mice. Collectively, these results indicated that the anti-metastatic effect of alpha -GalCer is mainly mediated by NK cells, which are activated secondarily by IFN-gamma produced by alpha -GalCer-activated NKT cells, in a perforin-independent manner.

Animals↗

[Pulmonary surgery for pulmonary lesion with pulmonary tuberculosis or of tuberculosis].

Nine patients with pulmonary tuberculosis underwent open chest surgery for pulmonary lesions of tuberculosis or other than tubercolosis. They were 1 case of lung cancer, 4 cases of pneumothorax, 1 case of multi drug resistant pulmonary tuberculosis and 3 cases of tuberculoma. Postoperative complications developed in 3 cases including 2 of pneumothorax and 1 of lung collapse.

Adolescent↗

Inhibition of thrombin by sulfated polysaccharides isolated from green algae.

Eight different sulfated polysaccharides were isolated from Chlorophyta. All exhibited thrombin inhibition through a heparin cofactor II (HCII)-dependent pathway, and their effects on the inhibition of thrombin were more potent than those of heparin or dermatan sulfate. In particular, remarkably potent thrombin inhibition was found for the sulfated polysaccharides isolated from the Codiales. In the presence of these sulfated polysaccharides, both the recombinant HCII (rHCII) variants Lys(173)-->Leu and Arg(189)-->His, which are defective in interactions with heparin and dermatan sulfate, respectively, inhibited thrombin in a manner similar to native rHCII. This result indicates that the binding site of HCII for each of these eight sulfated polysaccharides is different from the heparin- or dermatan sulfate-binding site. All the sulfated polysaccharides but RS-2 significantly stimulated the inhibition of thrombin by an N-terminal deletion mutant of HCII (rHCII-Delta74). Furthermore, hirudin(54-65) decreased only 2-5-fold the rate of thrombin inhibition by HCII stimulated by the sulfated polysaccharides, while HD22, a single-stranded DNA aptamer that binds exosite II of thrombin, produced an approximately 10-fold reduction in this rate. These results suggest that, unlike heparin and dermatan sulfate, the sulfated polysaccharides isolated from Chlorophyta activate HCII primarily by an allosteric mechanism different from displacement and template mechanisms.

Antithrombins↗

Quantitative Evaluation of Nystagmus by an Image-analysis System.

Purpose: We attempted to apply a newly developed image-analysis system for measurement and analysis of nystagmus.Method: Eye movements were recorded by digital video through a head-mounted charge coupled device (CCD) camera. The recorded movie was converted into black and white in order to detect the area of the pupil. Horizontal and vertical eye positions were determined by calculating the centroid of the pupil. Torsional angle was calculated using the iris striate pattern around the pupillary margin.Results: The parameters (amplitude, cycle, etc.) of nystagmus were calculated easily by the new image-analysis system from the recorded images. As examples, the foveation period was measured accurately in a case of jerky-type congenital nystagmus. Very regular cycles of intorsional attack period were revealed in a case of superior oblique myokymia. A case of cork-screw-like nystagmus showed a characteristic combination of large and small cycles unassociated with torsion.Conclusion: This image-analysis system was useful for quantitative analysis of nystagmus, and especially for measurement of torsion. Detailed waveforms and specific rhythms of nystagmus, which could not be recognized by observation, were demonstrated by this system.

Journal Article↗

Circadian component influences the photoperiodic induction of diapause in a drosophilid fly, Chymomyza costata.

The last-instar larvae of a drosophilid fly, Chymomyza costata enter diapause in response to the dark-phases longer than 9 h (Yoshida, T., Kimura, M.T., 1995. The photoperiodic clock in Chymomyza costata. Journal of Insect Physiology 41, 217-222). In order to switch the developmental programming of the sensitive larvae from continuous development to diapause, after they were transferred from the short (8 h) to the long (14 h) dark-phase, significantly less time (1-2 days) was required when the dark-phase was abruptly and asymmetrically extended into the evening, than when it was extended symmetrically into both morning and evening (2-3 days), or asymmetrically into the morning hours (4-6 days). Diapause was also induced in 40-70% of sensitive larvae that were reared under the gradually shortening light-phase (from 16 h to 2 h, by 1 h in each cycle), despite that the dark-phase remained constant and short (8 h). Larvae developed continuously, however, when reared under the gradually extending light-phase (from 16 h to 24 h) and a constantly short dark-phase. We interpret such results, with the help of the two-oscillator model of circadian rhythmicity (Pittendrigh, C.S., Daan, S., 1976. A functional analysis of circadian pacemakers in nocturnal rodents. V. Pacemaker structure: A clock for all seasons. Journal of Comparative Physiology A 106, 333-355), as indicating that two mutually coupled oscillators (evening and morning) differing in their entrainability may participate in measuring of the dark-phase duration. The levels of dopamine (DA) and serotonin (5-HT) in the larval CNS transiently increased (by up to 20%) after the dusk, while no apparent change was observed during the dawn. The dusk-related increase was observed also after the asymmetric extension of the dark-phase into evening, while the asymmetric extension into morning had no effect on the levels of the DA and 5-HT.

Journal Article↗

Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde.

3,4-Dihydroxyphenylacetaldehyde (DOPAL) has been reported to be a toxic metabolite formed by the oxidative-deamination of dopamine (DA) catalyzed by monoamine oxidase. This aldehyde is either oxidized to 3,4-dihydroxyphenylacetic acid (DOPAC) by aldehyde dehydrogenase, an NAD-dependent enzyme or reduced to 3, 4-dihydroxyphenylethanol (DOPET) by aldehyde or aldose reductase. In the present study we examined whether levels of DOPAL are elevated by inhibition of the mitochondrial respiratory chain. Using inhibitors of mitochondrial complexes I, II, III and IV we found that inhibition of complex I and III increased levels of DOPAL and DOPET. Nerve growth factor-induced differentiation of PC12 cells markedly potentiated DOPAL and DOPET accumulation in response to metabolic stress. DOPAL was toxic to differentiated PC12 as well as to SK-N-SH cell lines. Because complex I dysfunction has been implicated in the pathogenesis of Parkinson's disease, the accumulation of DOPAL may explain the vulnerability of the dopaminergic system to complex I inhibition. The rapid appearance of DOPAL and DOPET after inhibition of complex I may be a useful early index of oxidative stress in DA-forming neurons.

3,4-Dihydroxyphenylacetic Acid↗

Critical contribution of liver natural killer T cells to a murine model of hepatitis.

Natural killer T (NKT) cells constitute a distinct subpopulation of T cells with a unique antigen specificity, prompt effector functions, and an unusual tissue distribution. NKT cells are especially abundant in the liver, but their physiological function in this organ remains unclear. In the present study, we examined the possible contribution of NKT cells to a murine model of hepatitis induced by i.v. injection of Con A. CD1-deficient mice lacking NKT cells were highly resistant to Con A-induced hepatitis. Adoptive transfer of hepatic NKT cells isolated from wild-type mice, but not from FasL-deficient gld mice, sensitized CD1-deficient mice to Con A-induced hepatitis. Furthermore, adoptive transfer of hepatic mononuclear cells from wild-type mice, but not from CD1-deficient mice, sensitized gld mice to Con A-induced hepatitis. Upon Con A administration, hepatic NKT cells rapidly up-regulated cell surface FasL expression and FasL-mediated cytotoxicity. At the same time, NKT cells underwent apoptosis leading to their rapid disappearance in the liver. These results implicated FasL expression on liver NKT cells in the pathogenesis of Con A-induced hepatitis, suggesting a similar pathogenic role in human liver diseases such as autoimmune hepatitis.

Adoptive Transfer↗

Plasmatocyte spreading peptide (PSP1) and growth blocking peptide (GBP) are multifunctional homologs.

Recently, we identified Plasmatocyte spreading peptide (PSP1) from the moth Pseudoplusia includens and reported that it mediates adhesion of hemocytes to foreign surfaces. PSP1 is structurally very similar to three classes of peptides identified earlier from other species of Lepidoptera: growth blocking peptide (GBP) originally identified in Pseudaletia separata, and a series of related peptides from other species designated as paralytic (PP) or cardioactive (CAP) peptides. In this study, we conducted parallel experiments in P. includens and P. separata to determine whether PSP1 and GBP have distinct or multiple biological activities. Both peptides affected the adhesive state of hemocytes from each moth very similarly. PSP1 and GBP exhibited significant growth blocking and paralytic activity in P. separata. Both peptides also had growth blocking activity in P. includens although larvae had to be injected with higher doses of each peptide to reduce weight gain than was observed for P. separata. However, GBP and PSP1 had little paralytic activity in P. includens. Collectively, our results indicate that GBP and PSP1 are multifunctional, but that some interspecific variation also exists in their growth blocking and paralytic activities. We suggest that all PSP1, GBP, PP and CAP family members are homologs that likely have multiple biological activities. Based upon the unique consensus sequence of their N termini, we propose that these molecules be henceforth referred to as members of the "ENF" peptide family.

Journal Article↗

Activation of heparin cofactor II by calcium spirulan.

Heparin cofactor II (HCII) is a plasma serine protease inhibitor whose ability to inhibit alpha-thrombin is accelerated by a variety of sulfated polysaccharides in addition to heparin and dermatan sulfate. Previous investigations have indicated that calcium spirulan (Ca-SP), a novel sulfated polysaccharide, enhanced the rate of inhibition of alpha-thrombin by HCII. In this study, we investigated the mechanism of the activation of HCII by Ca-SP. Interestingly, in the presence of Ca-SP, an N-terminal deletion mutant of HCII (rHCII-Delta74) inhibited alpha-thrombin, as native recombinant HCII (native rHCII) did. The second-order rate constant for the inhibition of alpha-thrombin by rHCII-Delta74 was 2.0 x 10(8) M(-1) min(-1) in the presence of 50 microgram/ml Ca-SP and 10, 000-fold higher than in the absence of Ca-SP. The rates of native rHCII and rHCII-Delta74 for the inhibition of gamma-thrombin were increased only 80- and 120-fold, respectively. Our results suggested that the anion-binding exosite I of alpha-thrombin was essential for the rapid inhibition reaction by HCII in the presence of Ca-SP and that the N-terminal acidic domain of HCII was not required. Therefore, we proposed a mechanism by which HCII was activated allosterically by Ca-SP and could interact with the anion-binding exosite I of thrombin not through the N-terminal acidic domain of HCII. The Arg(103) --> Leu mutant bound to Ca-SP-Toyopearl with normal affinity and inhibited alpha-thrombin in a manner similar to native rHCII. These results indicate that Arg(103) in HCII molecule is not critical for the interaction with Ca-SP.

Binding Sites↗

Antibody response to toxic shock syndrome toxin-1 of Staphylococcus aureus in dairy cows.

Antibody response to toxic shock syndrome toxin-1 (TSST-1) of Staphylococcus aureus in dairy cows was examined by enzyme linked immunosorbent assay (ELISA). Serum antibody to TSST-1 was not detected in 39 (76.5%) of 51 calves, which were 1-6 months of age. In contrast, TSST-1 antibody was demonstrated in 1728 (72.6%) of 2380 lactating cows housed on 36 dairy farms. The ELISA values of antibody ranged from 0.2 to 3.0 OD and presented a distribution with the peak at 1.6 OD. The mean ELISA value differed between farms, and it increased slightly along with parturient history. Somatic cell counts of milk from 174 lactating cows was compared with TSST-1 antibody and tst1,000,000 cells per ml. The mean ELISA values in milk were lower than those of sera, but they rose as somatic cells increased. The tst gene of S. aureus detected in 76.0-86.2% of the milk samples containing somatic cells > 500,000 cells per ml, a level which indicates mastitis. The data suggests that many lactating cows may be infected by TSST-1- producing S. aureus.

Animals↗

CD27-mediated activation of murine NK cells.

CD27, a member of the TNF receptor superfamily, has been implicated in T cell activation, T cell development, and T cell-dependent Ab production by B cells. In the present study we examined the expression and function of CD27 on murine NK cells. Murine NK cells constitutively expressed CD27 on their surface. Stimulation with immobilized anti-CD27 mAb or murine CD27 ligand (CD70) transfectans solely could induce proliferation and IFN-gamma production of freshly isolated NK cells and enhanced the proliferation and IFN-gamma production of anti-NK1.1-sutimulated NK cells. Although NK cell cytotoxicity was not triggered by anti-CD27 mAb or against CD70 transfectants, prestimulation via CD27 enhanced the cytotoxic activity of NK cells in an IFN-gamma-dependent manner. These results suggest that CD27-mediated activation may be involved in the NK cell-mediated innate immunity against virus-infected or transformed cells expressing CD70.

Adjuvants, Immunologic↗