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Biomedical subjects

Y Yamamoto

Publications and source records attributed to Y Yamamoto.

At least 109 records · Page 6Linked to original sources

All-silicon quantum computer.

A solid-state implementation of a quantum computer composed entirely of silicon is proposed. Qubits are 29Si nuclear spins arranged as chains in a 28Si (spin-0) matrix with Larmor frequencies separated by a large magnetic field gradient. No impurity dopants or electrical contacts are needed. Initialization is accomplished by optical pumping, algorithmic cooling, and pseudo-pure state techniques. Magnetic resonance force microscopy is used for ensemble measurement.

Journal Article↗

Cimetidine modulates the antigen presenting capacity of dendritic cells from colorectal cancer patients.

Cimetidine, a H(2) receptor antagonist, has been reported to improve survival in gastrointestinal cancer patients. These effects have largely been attributed to the enhancing effects of cimetidine on the host's antitumour cell-mediated immune response, such as inhibition of suppressor T lymphocyte activity, stimulation of natural killer cell activity and increase of interleukin-2 production from helper T lymphocytes. We conducted an in vitro study on the effects of cimetidine on differentiation and antigen presenting capacity of monocyte-derived dendritic cells from advanced colorectal cancer patients and normal controls. As a result, an investigation of expression of surface molecules associated with dendritic cells by flow cytometric analyses showed that cimetidine had no enhancing effect on differentiation of dendritic cells from cancer patients and normal controls. An investigation of [(3)H]thymidine incorporation by allogeneic mixed lymphocyte reactions revealed that cimetidine increased the antigen presenting capacity of dendritic cells from both materials. Moreover, a higher antigen presenting capacity was observed in advanced cancer patients compared to normal controls. These effects might be mediated via specific action of cimetidine and not via H(2) receptors because famotidine did not show similar effects. Our results suggest that cimetidine may enhance the host's antitumour cell-mediated immunity by improving the suppressed dendritic cells function of advanced cancer patients.

Adult↗

Measurements of cosmic-ray low-energy antiproton and proton spectra in a transient period of solar field reversal.

The energy spectra of cosmic-ray low-energy antiprotons ( *p's) and protons ( p's) have been measured by BESS in 1999 and 2000, during a period covering reversal at the solar magnetic field. Based on these measurements, a sudden increase of the *p/p flux ratio following the solar magnetic field reversal was observed, and it generally agrees with a drift model of the solar modulation.

Journal Article↗

Electron entanglement via a quantum dot.

This Letter presents a method of electron entanglement generation. The system under consideration is a single-level quantum dot with one input and two output leads. The leads are arranged such that the dot is empty, single-electron tunneling is suppressed by energy conservation, and two-electron virtual cotunneling is allowed. Such a configuration effectively filters the singlet-state portion of a two-electron input, yielding a nonlocal spin-singlet state at the output leads. Coulomb interaction mediates the entanglement generation, and, in its absence, the singlet state vanishes. This approach is a four-wave mixing process analogous to the photon entanglement generated by a chi((3)) parametric amplifier.

Journal Article↗

Atracurium and vecuronium block nicotine-induced carotid body chemoreceptor responses.

BACKGROUND: Vecuronium depresses carotid body chemosensitivity during hypoxia. We hypothesized that this is caused by inhibition of cholinergic transmission of the carotid body. METHODS: The carotid body with its sinus nerve was removed en bloc from thiopentone-anaesthetized adult male New Zealand rabbits and perfused in vitro with modified Tyrodes buffer solution at constant perfusion pressure, temperature, a buffer pH of 7.4 and normocapnia. Chemoreceptor discharge and spike frequencies (fx) were recorded from the whole sinus nerve after administration of 500 microg nicotine, given as duplicated controls and thereafter following 30 min perfusion of equipotent concentrations of atracurium (28.1 microM) or vecuronium(10 microM), after 30 min of neostigmine perfusion (9.2 microM) and finally after 30 min wash-out with buffer solution only. A short-lasting hypoxic test was performed before and at the end of the experimental period to confirm the responsiveness and validity of the preparation. RESULTS: Atracurium (n = 7) and vecuronium (n = 6) reduced chemoreceptor responses to nicotine by 70 +/- 30% and 66 +/- 19% (SEM) (P<0.05). Chemoreceptor discharges showed full recovery after neostigmine in the atracurium group and partial recovery in the vecuronium group (P<0.05). Finally, after wash-out the chemoreceptor responses to nicotine had fully recovered in both groups. CONCLUSION: Atracurium and vecuronium in equipotent concentrations block nicotine-induced chemoreceptor responses of the carotid body.

Animals↗

Impaired activity of plasma von Willebrand factor-cleaving protease may predict the occurrence of hepatic veno-occlusive disease after stem cell transplantation.

Hepatic veno-occlusive disease (VOD) is a life-threatening complication after stem cell transplantation (SCT), characterized by thrombus formation in hepatic venules leading to a symptom triad of hyperbilirubinemia, hepatomegaly, and ascites. Multifactorial defects in the hemostatic system may contribute to its pathogenesis, but its remains to be investigated. Unusually large VWF multimers (UL-VWFMs), produced in and released from vascular endothelial cells, are most biologically active in the interaction with platelets under a high shear stress. UL-VWFMs are cleaved and degraded into smaller VWFMs by a specific liver producing plasma protease, termed VWF-cleaving protease (VWF-CPase), which has recently been identified as a metalloprotease solely produced in liver, termed ADAMTS13. Herein, we studied the correlation between plasma VWF-CPase activity and UL-VWFMs in 21 patients who received SCT, seven patients with VOD and 14 patients without VOD. In non-VOD patients, activities (mean +/- 1s.d.) of VWF-CPase were 78 +/- 17% of the control before the conditioning regimen, 76 +/- 18% on day 0, 64 +/- 19% on day 7, 57 +/- 23% on day 14, 68 +/- 13% on day 21 and 79 +/- 19% on day 28 after SCT. The respective values in VOD patients were 32 +/- 19%, 27 +/- 15%, 18 +/- 11%, 22 +/- 18%, 26 +/- 22% and 12 +/- 4%. Thus, VWF-CPase activity was significantly reduced in VOD patients, even before the conditioning regimen, and such a difference was not found in other laboratory tests. However, despite such a clear difference, UL-VWFMs were present in plasmas of both patient groups, together with the increase of VWF antigen and ristocetin cofactor activity. These results indicate that the measurement of this enzyme activity is extremely useful in predicting the occurrence of VOD prior to a demonstration of its direct involvement in its pathogenesis.

ADAM Proteins↗

Selective apoptosis of tandemly duplicated FLT3-transformed leukemia cells by Hsp90 inhibitors.

An internal tandem duplication of the juxtamembrane (JM) domain of FLT3, a family of ligand-activated receptor tyrosine kinases, has been found in 20% of cases of acute myeloid leukemia (AML), and this mutation is correlated with leukocytosis and a poor prognosis. As a therapeutic approach, we previously reported that herbimycin A (HA) inhibited the growth of tandemly duplicated FLT3 (TDFLT3)-transformed cells (Leukemia 2000; 14: 374). Here, we have investigated the mechanism behind the cytotoxicity of HA, an ansamycin derivative which is now known to target Hsp90. The treatment with HA or another Hsp90 inhibitor, radicicol, induced selective apoptosis in TDFLT3-transformed 32D cells (TDFLT3/32D). The tyrosine-phosphorylation of TDFLT3 was inhibited by HA, whereas FLT3 ligand-induced phosphorylation of wild-type FLT3 (WtFLT3) was not. The downstream signal molecules MAPK, Akt and STAT5a were also dephosphorylated by HA in TDFLT3/32D. Immunoprecipitation analysis showed that TDFLT3 but not WtFLT3 formed a complex with Hsp90, and that the HA treatment dissociated TDFLT3 from the Hsp90 chaperone complex. These findings imply that targeting of Hsp90 will facilitate the development of anti-TDFLT3 therapy, and that Hsp90 is closely involved in the oncogenic activation of FLT3.

Animals↗

Biphasic effects of substance P on respiratory activity and respiration-related neurones in ventrolateral medulla in the neonatal rat brainstem in vitro.

The effects of substance P (SP) on respiratory activity in the brainstem-spinal cord preparation from neonatal rats (0-4 days old) were investigated. The respiratory activity was recorded from C4 ventral roots and intracellularly from three types of respiration-related neurones, i.e. pre-inspiratory (or biphasic E), three subtypes of inspiratory; expiratory and tonic neurones in the ventrolateral medulla (VLM). After the onset of SP bath application (10 nM-1 microM) a dose-dependent decline of burst rate (by 48%) occurred, followed by a weaker dose-dependent increase (by 17.5%) in burst rate. The biphasic effect of SP on inspiratory burst rate was associated with sustained membrane depolarization (in a range of 0.5-13 mV) of respiration-related and tonic neurones. There were no significant changes in membrane resistance in any type of neurones when SP was applied alone or when synaptic transmission was blocked with tetrodotoxin (TTX). The initial depolarization was associated with an increase in inspiratory drive potential (by 25%) as well as in bursting time (by 65%) and membrane excitability in inspiratory and pre-inspiratory neurones, which corresponded to the decrease in burst rate (C4 activity). The spiking frequency of expiratory and tonic neurones was also increased (by 36 and 48%). This activation was followed by restoration of the synaptic drive potential and bursting time in inspiratory and to a less extent in pre-inspiratory neurones, which corresponded to the increase in burst rate. The discharge frequency of expiratory and tonic neurones also decreased to control values. This phase followed the peak membrane depolarization. At the peak depolarization, SP reduced the amplitude of the action potential by 4-8% in all types of neurones. Our results suggest that SP exerts a general excitatory effect on respiration-related neurones and synaptic coupling within the respiratory network in the VLM. The transient changes in neuronal activity in the VLM may underlie the biphasic effect of SP in the brainstem respiration activity recorded in C4 roots. However, the biphasic effect of SP on inspiratory burst rate seems to be also defined by the balance in activity of other SP-sensitive systems and neurones in the respiratory network in the brainstem and spinal cord, which can modify the activity of medullary respiratory rhythm generator.

Animals↗

Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle.

Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage-gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea-pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM), suramin (10 microM) and tetrodotoxin (1 microM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 microM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 microM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L-type voltage-gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.

Action Potentials↗

Use of a highly sensitive quantitative telomerase assay in intracytoplasmic sperm injection programmes for the treatment of 47,XXY non-mosaic Klinefelter men.

We evaluated the role of the sensitive quantitative telomerase assay (SQTA) in the management of men with non-mosaic Klinefelter's syndrome (KS). Diagnostic testicular biopsy (DTB) was performed in 24 men with KS. A part of the DTB was stained and the remaining fragment was processed for the SQTA. After 3-18 months, a therapeutic testicular biopsy (TTB) was performed in the same testicle and the recovered specimens were processed to identify spermatozoa. Men with a SQTA outcome equal to 0.00 Units microg-1 protein (n = 7) demonstrated therapeutic testicular biopsy material that was negative for spermatogenic cells. In five men with a SQTA outcome of 8.11-38.03 Units microg-1, the most advanced germ cell was the spermatogonium/primary spermatocyte. In the remaining 12 men, the most advanced spermatogenic cell in the TTB was the spermatozoon. In these men, the SQTA outcome was equal to 25.76-92.68 Units microg-1 protein. Using 39.00 Units microg-1 protein as a cut-off value, the accuracy of the SQTA in identifying men positive for spermatozoa was 91.6%. It appears that the SQTA has a role for identifying non-mosaic KS men who have testicular spermatozoa.

Adult↗

Metabolism and urinary excretion of a new quinoline anticancer drug, TAS-103, in humans.

1. TAS-103, a novel condensed quinoline derivative, has been developed as an anticancer drug targeting topoisomerases I and II. 2. The purpose of the present study was to characterize the metabolism and urinary excretion of TAS-103 after the intravenous infusion of a single dose to patients in Phase I clinical trials. 3. Five metabolites were detected using high-performance liquid chromatography (HPLC) photodiode array and a precursor scan by liquid chromatography mass spectrometry mass spectrometry (LC/MS/MS). 4. Structures of the five metabolites were determined using the results of enzymatic hydrolysis and the analysis of production mass spectra obtained by LC/MS/MS, and by comparing HPLC retention times and UV, mass and production mass spectra of authentic standards. 5. The metabolites were identified as demethyl-TAS-103 glucuronide (DM-TAS-103-G), TAS-103 glucuronide (TAS-103-G), TAS-103 glucuronide N-oxide (NO-TAS-103-G), demethyl-TAS-103 (DM-TAS-103) and TAS-103 N-oxide (NO-TAS-103). 6. The mean total amount of TAS-103 and TAS-103-G in urine was only 6.03% of the dose, suggesting that urine is not the main elimination route. TAS-103 was extensively metabolized, and a small percentage of the parent drug (0.41%) was found in urine.

Aminoquinolines↗

Comparison of 201 Tl- with 67 Ga single photon emission tomography in the diagnosis of head and neck cancer recurrence.

The purpose of this study was to evaluate the usefulness of 201Tl single photon emission tomography (SPET) in comparison with 67Ga SPET for distinguishing recurrent tumours in patients previously treated for head and neck cancer. A total of 37 patients with suspicion of recurrent cancer were investigated. SPET images with 201Tl were acquired 10min (early) and 3h (delayed) and SPET images with 67Ga were acquired 72h, after injection. The visual and semiquantitative (T/N ratio) analysis were performed. On visual analysis, results from early 201Tl SPET were the same as those from delayed 201Tl SPET. The sensitivity, specificity and accuracy of the diagnosis of local recurrence using 201Tl SPET were all 100%. The three values using 201Tl SPET for neck lymph node metastases were 73%, 100% and 91%. The corresponding values using 67Ga SPET for local recurrence were 57%, 100% and 89%, respectively, and those using 67Ga SPET for neck lymph node metastases 55%, 100% and 84%, respectively. In the semiquantitative analysis, there was a statistically higher T/N ratio obtained using 201Tl when compared with 67Ga. 201Tl early SPET, especially, has the potential to replace 67Ga SPET in the follow-up of patients with head and neck cancer.

Adult↗

99mTc-MIBI and 201Tl SPET in the detection of recurrent brain tumours after radiation therapy.

The purpose of this study was to evaluate whether Tc-hexakis-2-methoxyisobutylisonitrile ( Tc-MIBI) or Tl single photon emission tomography (SPET) could detect recurrent tumours in patients with previous radiation therapy for brain tumours. Dual SPET with Tc-MIBI and Tl was performed in 21 patients suspected of having recurrent brain tumours. SPET images were acquired 15 min (early) and 2 h (delayed) after injection. The ratio of the average counts for the region of interest in the lesion area and its mirror image in normal brain tissue was obtained. Early and delayed ratios were calculated. On the basis of histological and/or clinical findings, the final diagnosis was considered as recurrent tumours in 15 patients and radiation necrosis in six. Both ratios using Tc-MIBI and Tl were significantly higher in recurrent tumours than in radiation necrosis. Based on a cut-off of 5.89 of the early ratio using Tc-MIBI to distinguish between recurrent tumours and radiation necrosis, the accuracy was 90%. Based on a cut-off of 6.77 of the delayed ratio using Tc-MIBI, the accuracy was 86%. The corresponding values using cut-offs of 2.40 and 1.85 with Tl were 90% and 86%, respectively. However, within recurrent tumours, both ratios for Tc-MIBI were significantly higher than those for Tl. Early Tc-MIBI SPET may be especially useful for the detection of recurrent tumours in patients who have previously undergone radiation therapy for brain tumours.

Adult↗

Identification of a novel gelsolin truncate in the vertical and metastatic phase malignant melanomas.

Examination of 38 human melanoma samples by Western blotting analysis with anti-gelsolin antibodies showed that a new 85 kDa truncated gelsolin (GSNp85), co-expressed with wild-type gelsolin, was frequently expressed in vertical growth phase melanomas (Clark level II-IV) and metastatic growth phase melanomas. The GSNp85 truncate was not expressed in radial growth phase melanomas (Clark level I), acquired naevi, other skin cancers or normal skin tissues. Peptide-sequencing analysis revealed that GSNp85 lacks the C-terminal domain of wild-type gelsolin at the region containing the caspase-8 recognition site IETD. Caspase-8 processing was detected in GSNp85-positive but not GSNp85-negative melanomas. These data suggest that GSNp85 is a cleavage product of caspase-8 and may be useful as a new marker for the vertical or metastatic growth phase of malignant melanoma.

Amino Acid Sequence↗

Phospholipase C-dependent hydrolysis of phosphatidylcholine hydroperoxides to diacylglycerol hydroperoxides and its reduction by phospholipid hydroperoxide glutathione peroxidase.

We have shown that 1,2-diacylglycerol hydroperoxides activate protein kinase C (PKC) as efficiently as does phorbol ester [Takekoshi S, Kambayashi Y, Nagata H, Takagi T, Yamamoto Y, Watanabe K. Activation of protein kinase C by oxidized diacylglycerol. Biochem Biophys Res Commun 1995; 217: 654-660]. 1,2-Diacylglycerol hydroperoxides also stimulate human neutrophils to release superoxide whereas their hydroxides do not [Yamamoto Y, Kambayashi Y, Ito T, Watanabe K, Nakano M. 1,2-Diacylglycerol hydroperoxides induce the generation and release of superoxide anion from human polymorphonuclear leukocytes. FEBS Lett 1997; 412: 461-464]. One of the proposed mechanisms for the formation of 1,2-diacylglycerol hydroperoxides is the hydrolysis of phosphatidylcholine hydroperoxides by phospholipase C (PLC). To confirm this hypothesis, we incubated 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) liposomes containing PLPC hydroperoxides (PLPC-OOH) with Bacillus cereus PLC and found 1-palmitoyl-2-linoleoylglycerol (PLG) and its hydroperoxide (PLG-OOH) were produced. PLC hydrolyzed the two substrates without preference, as the yields of PLG and PLG-OOH were the same even though cholesterol was incorporated into liposomes to increase bilayer integrity. Phospholipid hydroperoxide glutathione peroxidase (PHGPX) reduced PLG-OOH to its hydroxide in the presence of glutathione while the conventional cytosolic glutathione peroxidase did not. These data suggest that PLC hydrolyzes oxidized biomembranes to give 1,2-diacylglycerol hydroperoxides for PKC stimulation but PHGPX may prevent neutrophil stimulation by reducing 1,2-diacylglycerol hydroperoxides to their hydroxides.

Animals↗

Extrinsic allergic alveolitis induced by the yeast Debaryomyces hansenii.

A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. Arterial blood gas analysis gave an oxygen tension of 8.38 kPa (63 Torr). Pulmonary function testing revealed restrictive ventilatory impairment with a reduction in the diffusing capacity. The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive development by a provocation test to the humidifier water. The yeast Debaryomyces Hansenii was the only microorganism cultured from the water of the humidifier. The double diffusion precipitating test and lymphocyte proliferative response was positive for an extract of D. Hansenii, providing evidence to incriminate this fungus. This is the first described case of EAA caused by D. Hansenii.

Aged↗

Changes in the peptidergic innervation in the carotid body of rats chronically exposed to hypercapnic hypoxia: an effect of arterial CO2 tension.

The abundance of neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the carotid body was examined in chronically hypercapnic hypoxic rats (10% O2 and 6-7% CO2 for 3 months), and the distribution and abundance of these four peptidergic fibers were compared with those of previously reported hypocapnic- and isocapnic hypoxic carotid bodies to evaluate the effect of arterial CO2 tension. The vasculature in the carotid body of chronically hypercapnic hypoxic rats was found to be enlarged in comparison with that of normoxic control rats, but the rate of vascular enlargement was smaller than that in the previously reported hypocapnic- and isocapnic hypoxic carotid bodies. In the chronically hypercapnic hypoxic carotid body, the density per unit area of parenchymal NPY fibers was significantly increased, and that of VIP fibers was unchanged, although the density of NPY and VIP fibers in the previously reportetd chronically hypocapnic and isocapnic hypoxic carotid bodies was opposite to that in hypercapnic hypoxia as observed in this study. The density of SP and CGRP fibers was decreased. These results along with previous reports suggest that different levels of arterial CO2 tension change the peptidergic innervation in the carotid body during chronically hypoxic exposure, and altered peptidergic innervation of the chronically hypercapnic hypoxic carotid body is one feature of hypoxic adaptation.

Animals↗