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Biomedical subjects

M Yamamoto

Publications and source records attributed to M Yamamoto.

At least 19 recordsLinked to original sources

Blood permeability of a novel ceramic scaffold for bone morphogenetic protein-2.

A functionally graded apatite (fg-HAp) with body fluid permeability was developed from bovine bone. The tissue reaction of fg-HAp and its efficacy as a scaffold for recombinant human bone morphogenetic protein-2 (BMP-2) were evaluated histomorphometrically, and a component of permeable fluid into the fg-HAp was analyzed by immunoblotting assay. The fg-HAp block (27 mm(3)) combined with and without BMP-2 (5 microg) was implanted subcutaneously in 4-week-old Wistar rats. Histological examination showed that the surface and bulk degradations of the fg-HAp proceeded extensively and giant cells appeared on the fg-HAp at 2 weeks. Body fluid permeation was found inside the fg-HAp, and the fluid component was immunopositive for albumin. In addition, albumin was detected as a main component among proteins collected from the in vivo implanted fg-HAp. The bioabsorption of the fg-HAp was accelerated as BMP-2-induced bone matured. Histomorphometrical analysis at 4 weeks in the BMP-2/fg-HAp implant showed 59.0% in the total volume of bone and marrow. These results indicate that fg-HAp is an innovative, bioabsorbable bioceramic with fluid permeability characteristic, and may become a biointegrated scaffold for bone engineering.

Albumins↗

Rottlerin synergistically enhances imatinib-induced apoptosis of BCR/ABL-expressing cells through its mitochondrial uncoupling effect independent of protein kinase C-delta.

Although the BCR/ABL tyrosine kinase inhibitor imatinib is highly effective for treatment of chronic myeloid leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (ALL), relapse with emerging imatinib-resistance mutations in the BCR/ABL kinase domain poses a significant problem. Here, we demonstrate that rottlerin, a putative protein kinase C-delta (PKCdelta)-specific inhibitor, acts synergistically with imatinib to induce apoptosis of BCR/ABL-expressing K562 and Ton.B210 cells. However, rottlerin inhibited neither PKCdelta nor BCR/ABL in these cells. On the other hand, rottlerin, previously characterized also as a mitochondrial uncoupler, transiently but significantly reduced mitochondrial membrane potential and gradually induced mitochondrial membrane permeabilization. Moreover, two other mitochondrial uncouplers, FCCP and DNP, very similarly induced apoptosis of BCR/ABL-expressing cells in a synergistic manner with imatinib. Imatinib synergistically enhanced mitochondrial membrane permeabilization induced by mitochondrial uncouplers, which led to release of cytochrome c into the cytoplasm and activation of caspases-3 and -9. Rottlerin also enhanced the cytotoxic effect of imatinib in leukemic cells from patients with CML blast crisis and Ph-positive ALL or a cell line expressing the imatinib-resistant E255K BCR/ABL mutant. The present study indicates that rottlerin synergistically enhances imatinib-induced apoptosis through its mitochondrial uncoupling effect independent of PKCdelta and may contribute to the development of new treatment strategy to overcome the imatinib resistance and to cure the BCR/ABL expressing leukemias.

Acetophenones↗

Surgical shunt closure via the lumen of an intrahepatic portal aneurysm.

BACKGROUND/AIMS: A surgical shunt closure via the lumen of an intrahepatic portal aneurysm was successfully performed in a 70-year-old Japanese woman with hepatic encephalopathy due to hyperammonemia. She had a 4-month history of repeated hepatic encephalopathy which persisted after treatment with oral medicine. Color Doppler ultrasonography and computed tomography revealed a cystic peripheral portal aneurysm, 4 cm in diameter, connecting the posterior branch of the portal vein to the short hepatic vein in the right lobe. METHODS: While performing the Pringle maneuver and clamping the inferior vena cava below the liver, the wall of the portal aneurysm was opened, and the site of inflow from the portal vein and the site of outflow to the hepatic vein via the lumen of the portal aneurysm were closed with interrupted sutures. RESULTS: The patient's postoperative course was uneventful, and she was discharged 12 days after surgery. 12 months after surgery, she had no recurrence of hyperammonemia or hepatic encephalopathy. CONCLUSION: Surgical shunt closure via the lumen of a portal aneurysm can be performed safely, easily, and completely with good vision.

Aged↗

Shift-invariant real-time edge-enhanced VanderLugt correlator using video-rate compatible photorefractive polymer.

We demonstrated a real-time shift-invariant VanderLugt correlator (VLC). The VLC was implemented with a 37 microm thick bis-triarylamine side-chain polymer matrix photorefractive (PR) polymer composite operating at 532 nm wavelength. Correlation selectivity was enhanced by real-time edge enhancement. The advantage of the VLC is that its architecture allows overcoming the PR material response speed. A correlator of this type enables a fast shift-invariant search of a large optical image database. A high degree of shift invariance in our correlator was possible because of the material thickness. The angular bandwidth of this material was measured experimentally in a degenerate four-wave mixing setup, and it was found to be in a very good agreement with the theory.

Journal Article↗

Negative Coulomb drag in a one-dimensional wire.

We observed negative Coulomb drag for parallel coupled quantum wires, in which electrons flow in the opposite directions between the wires. This only occurred under the conditions of strong correlation in the wires, that is, low density, high magnetic field, and low temperature, and cannot be addressed by a standard theory of momentum transfer. We propose a Coulomb drag model in which formation of a Wigner crystal state in the drag wire and a particle-like state in the drive wire is taken into account.

Journal Article↗

Seasonal variations in 228Ra/226Ra ratio within coastal waters of the Sea of Japan: implications for water circulation patterns in coastal areas.

In this study, low-background gamma-spectrometry was used to determine the (228)Ra/(226)Ra ratio of 131 coastal water samples from various environments around Honshu Island, Japan (mainly around Noto Peninsula) at 1-3 month intervals from April 2003 until September 2005. Spatial variation in (228)Ra/(226)Ra ratios was also assessed by analyzing 34 coastal water samples from five areas within the Sea of Japan during May and June 2004. The (228)Ra/(226)Ra ratio of coastal water from all sites around Noto Peninsula shows seasonal variation, with minimum values during summer ((228)Ra/(226)Ra=0.7) and maximum values during autumn-winter ((228)Ra/(226)Ra=1.7-2). This seasonal variation is similar to that recorded for coastal water between Tsushima Strait and Noto Peninsula. The measured lateral variation in (228)Ra/(226)Ra ratios within coastal water between Tsushima Strait and Noto Peninsula is only minor (0.5-0.7; May-June 2004). Coastal waters from two other sites (Pacific shore and Tsugaru Strait, north Honshu) show no clear seasonal variation in (228)Ra/(226)Ra ratio. These measured variations in (228)Ra/(226)Ra ratio, especially the temporal variations, have important implications for seasonal changes in patterns of coastal water circulation within the Sea of Japan.

Environmental Monitoring↗

A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer.

The aim of this study was to evaluate the efficacy and tolerability of gefitinib ('IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7-41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemo-naive Japanese patients with advanced NSCLC.

Adult↗

Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease.

LRRK2 G2019S is the most common known cause of Parkinson disease (PD) in patients of European origin, but little is known about its distribution in other populations. The authors identified two of 586 Japanese patients with PD heterozygous for the mutation who shared a haplotype distinct from that observed in Europeans. This suggests that G2019S originated from separate founders in Europe and Japan and is more widely dispersed than previously recognized.

Adolescent↗

Photorefractive polymer device with video-rate response time operating at low voltages.

The high-voltage bias required for video-rate compatible, efficient operation of a photorefractive polymer composite is reduced from 6-8 to 1.3 kV. At this low voltage, the device can hold erasable Bragg holograms with 80% efficiency in addition to having a video-rate response time. The transition of the hologram's state from thick to thin is analyzed in detail.

Journal Article↗

Correlations between bone mineral density and demographic, lifestyle, and biochemical variables in community-dwelling Japanese women 69 years of age and over.

INTRODUCTION: A few epidemiologic studies have comprehensively attempted to identify risk factors for low bone mineral density (BMD) in elderly Asian women. The purpose of this study was to identify demographic, lifestyle, and biochemical factors correlated with BMD in elderly Japanese women 69 years of age and over. METHODS: The study design was cross-sectional. The subjects were 583 ambulatory women aged 69 years and over, and their average age was 74.3 (SD 4.4) years. Predictor variables were age, reproductive history, anthropometric indices, grip strength, calcium intake, lifestyle information, and serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D (1,25(OH)(2)D), osteocalcin (OC), and undercarboxylated osteocalcin (ucOC) values. The outcome variable was forearm BMD measured with a DTX-200 osteometer. RESULTS: Simple linear regression analyses showed that BMD was significantly positively associated with body height, weight, body mass index, grip strength, serum albumin concentration, and "housework," and negatively associated with age, years since menopause, age at menarche, number of children, serum 1,25(OH)(2)D concentration, serum OC concentration, and ucOC concentration. The stepwise multiple regression analysis showed that weight (beta=0.00316, SE=0.00028, R(2)=0.180), age (beta=-0.00321, SE=0.00050, R(2)=0.108), log-transformed serum OC (beta=-0.0445, SE=0.0064, R(2)=0.053), log-transformed serum 1,25(OH)(2)D (beta=-0.0401, SE=0.0074, R(2)=0.050), "farmwork" (beta=0.00904, SE=0.00426, R(2)=0.005), and serum 25(OH)D concentration (beta=0.000281, SE=0.000120, R(2)=0.003) were significantly associated with BMD. CONCLUSION: It was concluded that body weight is a major predictor of forearm BMD among the factors measured in this study in independent Japanese women 69 years of age and over and that serum 1,25(OH)(2)D concentration may be associated with cortical BMD. Maintenance of body weight is very important for maintaining BMD in this population, unless a large weight aggravates obesity-related diseases. A follow-up study is needed to confirm these findings.

25-Hydroxyvitamin D 2↗

Intrauterine fetal demise following laser treatment in twin-to-twin transfusion syndrome.

OBJECTIVE: To evaluate the incidence, risk factors and consequences of intrauterine fetal demise (IUFD) of at least one twin in twin-to-twin transfusion syndrome (TTTS) treated by laser. DESIGN: Retrospective analysis. SETTING: Experience of a single centre between 1999 and 2004. POPULATION: A subgroup of 45 cases with fetal demise of one or both twins from a series of 120 cases of TTTS treated by laser. METHODS: All cases were entered prospectively into a dedicated database and the results were analysed retrospectively. MAIN OUTCOME MEASURES: Fetal demise prognostic factors, survival, fetal anaemia, brain lesions, neonatal death and intact survival. RESULTS: IUFD of one twin occurred in 40 of 120 cases (19 donors and 21 recipients). IUFD of both twins occurred in another five cases. From these 40 cases, miscarriage occurred in two and pregnancy termination was requested in another two cases because of antenatal brain lesions. Two neonates died and two presented severe morbidity, survivors were therefore neurologically normal at 6-44 months of life in 89% (32/36) of the cases. Univariate analysis showed that preoperative abnormal umbilical artery Doppler in the donor before laser treatment and in the recipient following laser treatment was associated with their demise. Incomplete coagulation was suspected in cases where anaemia or cerebral lesions developed following the death of the first twin (10). CONCLUSIONS: IUFD of one or both twins occurred in 45 of 120 (38%) cases of severe TTTS treated by laser. In these, separation of the placental circulations was incomplete in at least 22% (10/45) of the cases. Umbilical artery Doppler abnormalities before laser were found to be risk factors for the donors' demise following the procedure.

Anemia, Neonatal↗

Fludarabine induces apoptosis in chronic lymphocytic leukemia--the role of P53, Bcl-2, Bax, Mcl-1, and Bag-1 proteins.

The expression of P53, Bcl-2, Bax, Bag-1, and Mcl-1 proteins in CD5/CD20-positive B-chronic lymphocytic leukemia (B-CLL) cells from 30 typical CLL patients was evaluated before and after 48 h of incubation with 10(-6) M fludarabine using multiparametric flow cytometric analysis. Protein expression was correlated with annexin V expression, Rai modified clinical staging, lymphocyte doubling time, and previous treatment. Our main goal was to determine the predictive value of these proteins in CLL cells in terms of disease evolution. Bcl-2 expression decreased from a median fluorescence index (MFI) of 331.71 +/- 42.2 to 245.81 +/- 52.2 (P < 0.001) after fludarabine treatment, but there was no difference between viable cells (331.57 +/- 44.6 MFI) and apoptotic cells (331.71 +/- 42.2 MFI) before incubation (P = 0.859). Bax expression was higher in viable cells (156.24 +/- 32.2 MFI) than in apoptotic cells (133.56 +/- 35.7 MFI) before incubation, probably reflecting defective apoptosis in CLL (P = 0.001). Mcl-1 expression was increased in fludarabine-resistant cells and seemed to be a remarkable protein for the inhibition of the apoptotic process in CLL (from 233.59 +/- 29.8 to 252.04 +/- 35.5; P = 0.033). After fludarabine treatment, Bag-1 expression was increased in fludarabine-resistant cells (from 425.55 +/- 39.3 to 447.49 +/- 34.5 MFI, P = 0.012), and interestingly, this higher expression occurred in patients who had a short lymphocyte doubling time (P = 0.022). Therefore, we could assume that Bag-1 expression in such situation might identify CLL patients who will need treatment earlier.

Adult↗

A groundbreaking new suturing device: the Excalibur.

BACKGROUND: Laparoscopic knot tying can be stressful. We reported two simple techniques, known as the Thumbs up! knot and the Tornado knot. We have further refined these procedures with the development of a new needle holder, called the Excalibur suturing needle holder. MATERIALS: This forceps differ from most conventional forceps in that the hinge is designed to stick out. The large hinge is stored out of the way when the forceps are closed, to prevent the thread accidentally catching. RESULTS: The thread is hooked on the projected hinge, which resembles the heel of a high-heel shoe. By using this forceps, the laparoscopic knot tying becomes easier for not only well experienced but also less experienced surgeons. CONCLUSIONS: The Excalibur, with its high heel, can complete knots with simple straight-line motion, making knot tying easier. This forceps will help reduce the stresses associated with intra-corporeal knot tying.

Equipment Design↗

Mid-trimester hyperechogenic bowel in a fetus of Japanese origin carrying a new mutation of CFTR gene (L548Q).

We present a case of a fetus with hyperechogenic bowel, in which the L548Q mutation was detected in the mother of Japanese origin and the deltaF508 mutation in the father of Caucasian origin. The fetus proved to be compound heterozygous. Research into cystic fibrosis transmembrane conductance regulator (CFTR) mutations in this case was triggered by the fact that the fetus had a characteristic hyperechogenic bowel image with normal karyotype and no indications of intrauterine infections. Hyperechogenic bowel is highly indicative of a CFTR gene mutation. The incidence of cystic fibrosis (CF) in fetuses with mid-trimester hyperechogenic bowel is 5%, but once the most frequent mutations have been accounted for, rarer mutations must be investigated.

Abnormalities, Multiple↗

Interferon-gamma inhibits collagen phagocytosis in human fibroblasts by inducing subcortical actin assembly and reducing ability of beta1 integrin to bind to collagen.

OBJECTIVE: We investigated the possible roles of interferon-gamma (IFN-gamma) in modulation of extracellular and intracellular routes of collagen digestion by human fibroblasts. METHODS: Human gingival fibroblasts were treated with IFN-gamma, after which matrix metalloproteinase-1 (MMP-1) activation was determined. Following the IFN-gamma treatment, cells were further incubated with either activating antibody for beta1 integrin or actin monomer-sequestering agent latrunculin B before incubation with collagen-coated fluorescent beads. Thereafter, the binding and internalization of the beads were assessed. RESULTS: IFN-gamma had no significant effect on MMP-1 activation, however, it reduced the binding of collagen-coated beads in the minimum affinity range and, subsequently, internalization of the beads. The inhibitory effects of IFN-gamma were partially reversed by adding either the beta1 integrin activating antibody or latrunculin B. CONCLUSIONS: Although IFN-gamma does not appreciably moderate the extracellular route of collagen digestion by human fibroblasts, the reduced level of collagen phagocytosis by IFN-gamma in the cells may contribute to fibrosis in inflamed connective tissues. Further, IFN-gamma may decrease the binding of collagen and following phagocytosis in cells by inducing a subcortical actin assembly and reducing the ability of beta1 integrin to bind to collagen.

Actins↗

Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockades of IL-6 receptor downstream signaling, to suppress the proliferation of MM cells. Because MM cells are resistant to conventional adenoviral vector infection, we utilized infectivity-enhanced adenoviral vectors with an RGD4C motif in the adenoviral fiber-knob region (RGD-modified vector). In infectivity analysis, RGD-modified vectors were superior to unmodified controls in the majority of the MM cell lines tested. The overexpression of SOCS-1 using infectivity-enhanced adenoviral vectors achieved growth suppression in IL-6-dependent MM cells, but not in the IL-6-independent cells. IL-6-induced STAT3 phosphorylation was suppressed in IL-6-dependent cells, indicating that the signal transduction cascade of the IL-6 receptor signaling was blocked. In aggregate, SOCS-1 overexpression with RGD-modified adenoviral vectors achieved the antiproliferative effect in IL-6-dependent MM cells. These results provide an initial proof-of-principle of the anticancer effect of SOCS-1 expression vector as well as a promise for the future development of therapeutic modality for MM based on this vector.

Adenoviridae↗

The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context.

Adenoviral vectors are widely used in cancer gene therapy. After systemic administration however, the majority of the virus homes to the liver and the expressed transgene may cause hepatotoxicity. To restrict transgene expression to tumor cells, tumor- or tissue-specific promoters are utilized. The tumor antigen epithelial glycoprotein-2 (EGP-2), also known as Ep-CAM, is expressed in many cancers from different epithelial origins. In this study, the EGP-2 promoter was shown to restrict the expression of luciferase and thymidine kinase in an adenoviral context in different cell lines. In vivo, the EGP-2 promoter mediated efficient expression of luciferase in tumors but showed a 3-log lower activity in liver tissue when compared with the cytomegalovirus (CMV) promoter. Similarly, the EGP-2 promoter mediated specific cell killing after ganciclovir treatment in EGP-2-positive cells. Moreover, in vivo, this treatment regiment did not cause any rise in the liver enzymes aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT), demonstrating absence of liver toxicity. In contrast, CMV-mediated expression of thymidine kinase in combination with ganciclovir treatment resulted in high ASAT and ALAT values. This study demonstrates the value of the EGP-2 promoter to restrict transgene expression to a broad range of tumor types, thereby preventing liver toxicity.

Adenoviridae↗