Biomedical subjects

M Saitoh

Publications and source records attributed to M Saitoh.

At least 19 recordsLinked to original sources

PubMed2006

Fulde-Ferrell-Larkin-Ovchinnikov state in a perpendicular field of quasi-two-dimensional CeCoIn5.

A Fulde-Ferrell-Larkin-Ovchinnkov (FFLO) state was previously reported in the quasi-2D heavy fermion CeCoIn5 when a magnetic field was applied parallel to the ab plane. Here, we conduct 115In NMR studies of this material in a perpendicular field, and provide strong evidence for FFLO in this case as well. Although the topology of the phase transition lines in the H-T phase diagram is identical for both configurations, there are several remarkable differences between them. Compared to H parallelab, the FFLO phase for H perpendicularab is confined in a much narrower region at the low-T-high-H corner in the H-T plane, and the critical field separating the FFLO and non-FFLO superconducting states almost ceases to have a temperature dependence. Moreover, directing H perpendicularab results in a notable change in the quasiparticle excitation spectrum within the planar node associated with the FFLO transition.

Journal Article↗

PubMed2006

Execution of BMP-4-induced apoptosis by p53-dependent ER dysfunction in myeloma and B-cell hybridoma cells.

Bone morphogenic protein (BMP)-4 inhibits proliferation and induces the apoptosis of myeloma cells. However, little is known about the molecular mechanisms of how BMP-4 executes this apoptosis. In this report, we investigated the roles of p53 and the endoplasmic reticulum (ER) in BMP-4-induced apoptosis of mouse hybridoma HS-72 cells. We found that 3 ng/ml of BMP-4 is sufficient to induce the expression of proapoptotic proteins, puma and bax, in a p53-dependent mechanism, and facilitate Ca(2+) release from the ER to the cytosol, resulting in the activation of caspase-12 and ER dysfunction. Similarly to HS-72 cells, multiple myeloma cells with wild-type p53 genes show much higher sensitivity to BMP-4-induced apoptosis than cells without wild-type p53 genes, suggesting that wild-type p53 status is required for dysfunction of the ER during BMP-4-induced apoptosis in ER-enriched cells, such as hybridoma and myeloma cells. These findings demonstrate that the presence of wild-type p53 genes and enrichment of the ER determines the sensitivity to effective apoptosis by BMP-4, and suggest that ER stress-inducing agents would be valuable in the treatment of multiple myeloma.

Animals↗

PubMed2006

Chemical removal and recovery of phosphorus from excess sludge in a sewage treatment plant.

We describe a process for the recovery of phosphorus from excess sludge in a sewage treatment plant that currently uses polyaluminium chloride for chemical phosphorus removal. Instead, we employed alkaline dissolution of excess sludge with calcium phosphate precipitation to recover phosphorus from sewage. The recovery ratio for phosphorus from sewage using the phosphorus recovery system is approximately 50%. In addition, the amount of excess sludge in the phosphorus recovery system is approximately half that of conventional chemical phosphorus removal. Alkaline dissolution of excess sludge resulted in dissolution of aluminium into the supernatant. Furthermore, since dissolved aluminium can be reused as a coagulant, the phosphorus recovery system could be used to economize coagulant consumption. Operation and maintenance costs of the phosphorus recovery system are 25.9 U.S. cents per 1 m3 of sewage compared to 32.0 U.S. cents per 1 m3 of sewage for conventional chemical phosphorus removal, representing a decrease of 20% in the operation and maintenance costs.

Aluminum Chloride↗

PubMed2005

Observation of surface Andreev bound States of superfluid 3He by transverse acoustic impedance measurements.

Complex transverse acoustic impedance of the superfluid (3)He-B was measured at the frequencies of 10 to 80 MHz at 17.0 bar by a cw bridge method. The observed temperature dependence was well explained by the quasiclassical theory with random S-matrix model for a diffusive surface. The temperature dependence was influenced by pair breaking and by quasiparticle density of states at the surface, which was drastically modified from the bulk one by the presence of surface Andreev bound states.

Journal Article↗

PubMed2005

Texture in the superconducting order parameter of CeCoIn5 revealed by nuclear magnetic resonance.

We present a 115In NMR study of the quasi-two-dimensional heavy-fermion superconductor CeCoIn5 believed to host a Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state. In the vicinity of the upper critical field and with a magnetic field applied parallel to the ab plane, the NMR spectrum exhibits a dramatic change below T*(H) which well coincides with the position of reported anomalies in specific heat and ultrasound velocity. We argue that our results provide the first microscopic evidence for the occurrence of a spatially modulated superconducting order parameter expected in a FFLO state. The NMR spectrum also implies an anomalous electronic structure of vortex cores.

Journal Article↗

PubMed2005

Identification and frequency of a new HLA-A allele, A*030104.

We here identified a novel HLA-A allele, A*030104, which was found in a Japanese family. The direct sequencing revealed that A*030104 was identical to A*030101 except for a nucleotide substitution of GAG to GAA at codon 63 without an amino acid replacement. The frequencies of A*030104 and A*0301 including A*030104 in Japanese population (n = 22,360) were approximately 0.013 and 0.40%, respectively.

Alleles↗

PubMed2004

A role for Id in the regulation of TGF-beta-induced epithelial-mesenchymal transdifferentiation.

Epithelial-mesenchymal transdifferentiation (EMT) is a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors. EMT can be induced by transforming growth factor (TGF)-beta in mouse NMuMG mammary epithelial cells. Here, we demonstrate a central role of helix-loop-helix factors, E2A and inhibitor of differentiation (Id) proteins, in TGF-beta-induced EMT. Epithelial cells ectopically expressing E2A adopt a fibroblastic phenotype and acquire migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Id proteins interacted with E2A proteins and antagonized E2A-dependent suppression of the E-cadherin promoter. Levels of Id proteins were dramatically decreased by TGF-beta. Moreover, NMuMG cells overexpressed Id2 showed partial resistance to TGF-beta-induced EMT. Id proteins thus inhibit the action of E2A proteins on the expression of E-cadherin, but after TGF-beta stimulation, E2A proteins are present in molar excess of the Id proteins, thus over-riding their inhibitory function and leading to EMT.

Animals↗

PubMed2002

Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension.

Predispositions to essential hypertension and cardiovascular diseases are possibly associated with gene polymorphisms of the renin-angiotensin system. Gene polymorphisms of angiotensinogen and angiotensin-converting enzyme genes have been suggested to be risk factors for hypertension and myocardial infarction. Concerning the polymorphism of aldosterone synthase (CYP11B2) gene, earlier studies have shown inconsistent results in terms of its relation to hypertension. In the present case-control study, we investigated the association of -344T/C polymorphism in the promoter region of human CYP11B2 gene with genetic predisposition to hypertension. The genotype of -344T/C polymorphism was determined in essential hypertension subjects (n=250) and normotensive subjects (n=221). The distributions of three genotypes (TT, TC, and CC) were significantly different between the hypertensive and the normotensive groups (chi(2)=9.61, P=0.008). Namely, the frequency of C allele was higher in the hypertensive patients than in the normotensive subjects (34.2 vs 26.5%, P=0.010). Our data suggest that the -344C allele of CYP11B2 gene polymorphism is associated with the genetic predisposition to develop essential hypertension.

Adult↗

PubMed2002

Amicrobial pustular dermatosis in two patients with immunological abnormalities.

We report two patients with severe amicrobial pustular dermatosis with immunological abnormalities: a 63-year-old woman with a 30-year-history of discoid lupus erythematosus and sicca syndrome, and a 35-year-old woman with high levels of gamma-globulinemia and positive antinuclear antibodies. Both patients presented with crusty and eroded erythematous plaques studded with aseptic pustules on the back, face, and scalp. Histological examination showed acanthosis, neutrophilic exocytosis to the epidermis, and neutrophilic and lymphocytic infiltration with nuclear dust in the dermis. These patients were diagnosed as having "amicrobial pustulosis associated with autoimmune diseases". The eruptions improved with combination treatment of oral prednisolone with cyclosporin A or diaminodiphenylsulphone. Although the pathogenesis remains unclear, amicrobial pustular dermatosis might be one of the cutaneous complications in autoimmune diseases.

Administration, Oral↗

PubMed2002

New mathematical model for accurate description of absorption kinetics of paracetamol given orally with a high calorie liquid meal.

OBJECTIVE: Gastric emptying (GE) of liquids is quantified as the rate of paracetamol absorption in clinical and research settings (paracetamol method). A conventional 1-compartment model assumes the first-order rate kinetics for paracetamol absorption. This assumption seems improper when paracetamol is coingested with a caloric liquid meal, because the caloric liquid leaves the stomach at a constant rate (zero-order process). Theories based on the 1-compartment model reveal that tmax and Cmax/AUCinfinity accurately reflect the rate of paracetamol absorption, but whether this is also the case when paracetamol is administered with a caloric liquid, has not been investigated. The aims of this study were to propose a new mathematical model for accurately describing absorptive behaviors of paracetamol added to a caloric liquid meal, and, using the model, to clarify the characteristics of tmax and Cmax/AUCinfinity as rate parameters. METHODS: Based on the newly developed model, tamx and Cmax/AUCinfinity were mathematically expressed in terms of GE rates. Subsequently, the characteristics of tmax and Cmax/AUCinfinity were elucidated by simulation works. RESULTS: The simulation study showed that both tamx and Cmax/AUCinfinity could reflect GE rates, tmax was a more sensitive index of GE than Cmax/AUCinfinity and tmax was less reliable than Cmax/AUCinfinity if GE is very rapid. CONCLUSIONS: In the paracetamol method using a caloric liquid test meal, tmax and Cmax/AUCinfinity are suitable for detecting delayed and rapid GE, respectively.

Absorption↗

PubMed2002

[Postintubation tracheal stenosis; problems associated with choice of management].

We experienced a case with tracheal stenosis due to postintubation damage, or so-called cuff stenosis. A 50-year-old man who attempted suicide by pounding nails into his head and chest using carpenter's tools was treated by endotracheal intubation and immediately underwent emergency surgery in July 2000. The patient was placed on artificial ventilation with oral endotracheal intubation, and a tracheostomy was performed 4 days after the operation. After that, his respiration recovered and he was weaned from the respirator. He was discharged 22 days after surgery with no respiratory symptoms. Two days after discharge, he complained of wheezing and dyspnea. Medical examination revealed that the cervical trachea had a severe circumferential stenosis 2.5 cm from the second tracheal cartilage. On retrospective inspection, the region of stenosis was compatible with the cuff site of the endotracheal tube used for the emergency operation. At first we tried nonoperative treatment, considering his mental state. However, we found that surgical treatment was ultimately necessary. A 2.5 cm sleeve resection of the trachea (5 tracheal cartilage rings) was performed, followed by end-to-end suture using 21 stitches with 4-0 MEDIFIT C thread. Pathologically, the surgical specimen showed degeneration and necrosis of tracheal cartilage with excessive growth of granulation tissue. These findings revealed that the etiologic basis of the tracheal stenosis was attributed to pressure necrosis by the cuff. The postoperative course was uneventful. Sixteen months after the surgery, the granulation tissue had not recurred, and problematic stenosis was not visible in the trachea. In this report, we discussed a reasonable management of postintubation tracheal stenosis. Tracheoplasty has been proposed as the most reliable method for treating tracheal stenosis. However, the best treatment in each case is still somewhat controversial because various nonoperative treatment methods are recently available, including laser phototherapy, argon plasma coagulation, mechanical dilatation, stent replacement, and drug treatment. Therefore, it is very important to judge properly the absolute indication for surgical treatment. If granulations are removed successfully by the above-described nonoperative methods, attempts at repair lead only to regrowth of granulation tissue as long as there is necrotic tracheal cartilage. Thus, the determinant of treatment methods is whether postintubation damage extends to tracheal cartilage or not. For now, there is no accurate diagnostic study for viability of cartilage preoperatively. In the literature, symptoms due to airway stenosis occurred rapidly within one month in the case of patients with necrosis of tracheal cartilage. We concluded that the period between extubation and development of symptoms is very informative in the management of postintubation tracheal stenosis. Surgical approaches should be selected for a patient with a rapid and progressive course after extubation when the patient can tolerate it.

Humans↗

PubMed2001

Mitochondrial coupling factor 6 is present on the surface of human vascular endothelial cells and is released by shear stress.

BACKGROUND: We showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, is present in the systemic circulation as a pressor substance in rats. We investigated the possibility of vascular endothelial cells as a source of circulating CF6. METHODS AND RESULTS: We used 2 cultured endothelial cell lines, human umbilical vein endothelial cells (HUVECs) and ECV 304 cells (transformed HUVECs), for this study. Immunofluorescence microscopy of both ECV 304 and HUVECs confirmed the surface-associated immunoreactivity of anti-CF6 antibody on the plasma membrane. The concentration of CF6 in the medium increased gradually with time in both ECV 304 and HUVECs in static conditions. Exposure of ECV 304 and HUVECs to a fluid shear stress enhanced the release of CF6: In ECV 304, the concentration of CF6 in the medium (ng. well(-1). 6 hours(-1)) was 2.1+/-0.8 at baseline, 4.3+/-0.8 after shear at 15 dynes/cm(2), and 57.7+/-8.4 after shear at 25 dynes/cm(2). CF6 contents in the cell homogenate and mitochondria were both significantly increased after exposure of ECV 304 to 6-hour shear at 15 dynes/cm(2), whereas they were unchanged after shear stress at 25 dynes/cm(2). The ratio of CF6 to GAPDH mRNA was enhanced significantly, by 1.8+/-0.2-fold, after 6-hour shear stress at 25 dynes/cm(2). Flow cytometry analysis revealed that the surface-associated CF6 was significantly increased in a 3-hour static condition after the previous exposure of the cells to shear stress for 3 hours. CONCLUSIONS: Vascular endothelial cells are a source of CF6, and shear stress regulates the release of the surface-associated CF6.

Cell Line↗

PubMed2001

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

Androstenedione↗

PubMed2001

Mammalian TOR: a homeostatic ATP sensor.

The bacterial macrolide rapamycin is an efficacious anticancer agent against solid tumors. In a hypoxic environment, the increase in mass of solid tumors is dependent on the recruitment of mitogens and nutrients. When nutrient concentrations change, particularly those of essential amino acids, the mammalian Target of Rapamycin (mTOR) functions in regulatory pathways that control ribosome biogenesis and cell growth. In bacteria, ribosome biogenesis is independently regulated by amino acids and adenosine triphosphate (ATP). Here we demonstrate that the mTOR pathway is influenced by the intracellular concentration of ATP, independent of the abundance of amino acids, and that mTOR itself is an ATP sensor.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress.

Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase (MAPKKK) that activates the JNK and p38 MAP kinase cascades and is activated in response to oxidative stress such as hydrogen peroxide (H(2)O(2)). A yeast two-hybrid screening identified a serine/threonine protein phosphatase 5 (PP5) as a binding partner of ASK1. PP5 directly dephosphorylated an essential phospho-threonine residue within the kinase domain of ASK1 and thereby inactivated ASK1 activity in vitro and in vivo. The interaction between PP5 and ASK1 was induced by H(2)O(2) treatment and was followed by the decrease in ASK1 activity. PP5 inhibited not only H(2)O(2)-induced sustained activation of ASK1 but also ASK1-dependent apoptosis. Thus, PP5 appears to act as a physiological inhibitor of ASK1-JNK/p38 pathways by negative feedback.

Animals↗

PubMed2001

Disparate effects of interleukin 11 and thrombopoietin on megakaryocytopoiesis in vitro.

The effects of interleukin-11 (IL-11) and thrombopoietin (TPO) on murine megakaryocytopoiesis were studied using a serum-free culture system. Acting alone, both IL-11 and TPO increased the number of acetylcholinesterase (AchE)(+)cells (megakaryocytes), the latter being more potent than the former. TPO, but not IL-11, increased the mean AchE activity per megakaryocyte (AchE activity/megakaryocyte). TPO increased both the number of megakaryocytes with high ploidy, and of those with low ploidy. In contrast, IL-11 increased only the number of megakaryocytes with high ploidy. The effect of TPO on megakaryocyte ploidy was stronger than that of IL-11. Both IL-11 and TPO increased the proportion of large megakaryocytes, but the latter was more potent than the former. While the stimulatory effects of IL-11 and TPO on the number of megakaryocytes were enhanced by IL-3 or stem cell factor (SCF), synergism of IL-11 or TPO with IL-3 or SCF in stimulating AchE activity/megakaryocyte was inconsistent. IL-11 and TPO stimulated the formation of colony-forming units of megakaryocyte in the presence of IL-3, but not alone, with similar maximum colony numbers for both cytokines. Our findings thus demonstrate that IL-11 principally stimulates megakaryocyte maturation rather than the proliferation of megakaryocytes, whereas TPO stimulates both.

Acetylcholinesterase↗

PubMed2001

Surface fluctuations of normal and superfluid 3He probed by Wigner solid dynamics.

Electron scattering from surface fluctuations on normal and superfluid 3He has been measured by its effect on the linewidth of the low-wave-vector transverse magnetophonon mode of the electron crystal (the Wigner solid) floating on the helium surface. The relaxation rate becomes anomalously low below 70 mK, and reaches a plateau at about 3 times less than its expected value before dropping further at the superfluid transition. The absence of such anomalous behavior on 4He suggests that the effect is specific to liquid 3He.

Journal Article↗

PubMed2001

Kinetic analysis of megakaryopoiesis induced by recombinant human interleukin 11 in myelosuppressed mice.

Recombinant human interleukin 11 (rhIL-11) has previously been shown to ameliorate thrombocytopenia in several animal models. To elucidate the mechanisms involved in rhIL-11-induced hematopoiesis, a kinetic analysis of megakaryopoiesis was performed in mitomycin C (MMC)-induced myelosuppressive mice. Mice intravenously injected with MMC (2 mg/kg) for two consecutive days from day -1 developed severe thrombocytopenia with a nadir of platelet counts at 24x10(4)/microl on day 12 and neutropenia. Treatment with rhIL-11 (500 microg/kg/day) from day 1 to 21 significantly ameliorated the degree and duration of thrombocytopenia and enhanced the platelet recovery, and also enhanced the recovery from neutropenia. In MMC-treated mice, the decreases in bone marrow megakaryocyte progenitors and megakaryocyte counts preceded the decrease in platelet counts by MMC treatment. RhIL-11 induced an increase in the number of megakaryocyte progenitors from day 4 to 14, followed by an increase in the megakaryocytes by day 20. There was a ploidy shift in megakaryocytes towards lower ploidy cells by day 9 in myelosuppressed mice. RhIL-11 caused a shift towards a higher ploidy with 32 and 64N on day 4, and 32N on day 14. These results suggest that rhIL-11 ameliorates the thrombocytopenia via the stimulation of both the maturation and commitment followed by the proliferation of megakaryocytic cells.

Alkylating Agents↗