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Biomedical subjects

N Yamamoto

Publications and source records attributed to N Yamamoto.

At least 199 records · Page 11Linked to original sources

Alternate magnetic fields potentiate monoamine oxidase activity in the brain.

Catecholamines and serotonin, which act as neurotransmitters and regulate blood circulation, are degraded by monoamine oxidase (MAO) [EC 1.4.3.4.] which exists two iso-enzymes named MAO-A and MAO-B. In this study, the effects of magnetic fields on MAO activity in the rat brain were examined. MAO-A activity was not changed in static magnetic fields (0.1-340 mT) or in 10-500 mT/s of alternate isosceles triangular magnetic fields (AITMF) (50 Hz). MAO-B activity was not changed in static magnetic fields (0.1-340 mT) and in 10, 34, 340, 95, 105, 110, and 340 mT/s of AITMF. However, it was increased to 114% in the 100 mT/s of AITMF. In 100 mT/s, Michaelis constant (K(m)) significantly decreased to 72%, suggesting that the affinity of the substrate to the enzyme also increased. These results indicate that only MAO-B was influenced by AITMF with 'active window' phenomenon, and suggest that AITMF might affect neural activity and hemodynamics by altering MAO-B.

Journal Article↗

Structural requirement for the two-step dimerization of human immunodeficiency virus type 1 genome.

Generation of RNA dimeric form of the human immunodeficiency virus type 1 (HIV-1) genome is crucial for viral replication. The dimerization initiation site (DIS) has been identified as a primary sequence that can form a stem-loop structure with a self-complementary sequence in the loop and a bulge in the stem. It has been reported that HIV-1 RNA fragments containing the DIS form two types of dimers, loose dimers and tight dimers. The loose dimers are spontaneously generated at the physiological temperature and converted into tight dimers by the addition of nucleocapsid protein NCp7. To know the biochemical process in this two-step dimerization reaction, we chemically synthesized a 39-mer RNA covering the entire DIS sequence and also a 23-mer RNA covering the self-complementary loop and its flanking stem within the DIS. Electrophoretic dimerization assays demonstrated that the 39-mer RNA reproduced the two-step dimerization process, whereas the 23-mer RNA immediately formed the tight dimer. Furthermore, deletion of the bulge from the 39-mer RNA prevented the NCp7-assisted tight-dimer formation. Therefore, the whole DIS sequence is necessary and sufficient for the two-step dimerization. Our data suggested that the bulge region regulates the stability of the stem and guides the DIS to the two-step dimerization process.

Capsid↗

Patients' understanding of their own disease and survival potential in patients with metastatic breast cancer.

PURPOSE: To investigate the effect of understanding their own disease by patients with metastatic breast cancer on their survival potential after being informed by their physician. PATIENTS AND METHODS: Two hundred and fourteen women with metastatic breast cancer who participated in a multi-institutional, randomized phase III trial (Japan Clinical Oncology Group (JCOG) Study 8808) were asked whether they understood their own disease after being given information about the clinical trial. They were classified into two groups on the basis of whether they understood or not. We estimated their survival after the time of registration and derived relative hazard ratios from Cox's proportional hazards model. RESULTS: There were 190 patients in the 'better understanding' group and 24 in the 'poor understanding' group. Median survival times after registration were 28.3 and 16.1 months, respectively. The 'better understanding' group showed a significant difference from the 'poor understanding' group (p = 0.016). In multivariate regression analysis, patients who did not understand still showed poorer survival than those who understood (hazard ratio = 2.09; 95% confidence interval (CI) 1.16-3.78; p = 0.014). CONCLUSION: These results support the supposition that patients' understanding of information about their disease may influence their survival. Thus, it is important to evaluate patients' recognition about information even after obtaining their consent. However, further investigation is needed to clarify the exact nature of this relationship.

Adult↗

Microarray fabrication with covalent attachment of DNA using bubble jet technology.

We have developed a method for fabricating DNA microarrays that uses a Bubble Jet ink jet device to eject 5'-terminal-thiolated oligonucleotides to a glass surface. The oligonucleotides are covalently attached to the glass surface by heterobifunctional crosslinkers that react with the amino group on the substrate and a thiol group on the oligonucleotide probe. Using this method, we fabricated DNA microarrays that carried 64 groups of 18-mer oligonucleotides encoding all possible three-base mutations in the mutational "hot spot" of the p53 tumor-suppressor gene. These were screened with a fluorescently labeled synthetic 18-mer oligonucleotide derived from the p53 gene, or segments of the p53 gene that had been PCR amplified from genomic DNA of two cell lines of human oral squamous cell carcinoma (SCC). This allowed us to discriminate between matched hybrids and 1 bp-mismatched hybrids.

Base Sequence↗

Natural disasters and alcohol consumption in a cultural context: the Great Hanshin Earthquake in Japan.

AIMS: To assess changes in alcohol consumption attributable to the Great Hanshin Earthquake to test the assumption that alcohol consumption increases after natural disasters. METHODS: Quarterly alcohol sales figures were compared for three periods: before, immediately after and subsequent to the Great Hanshin Earthquake in three areas of the Hyogo prefecture: the severely affected area, the moderately affected area and the unaffected area. Possible confounding by population movement, damage to retail outlets and normal variation in sales, was assessed. FINDINGS: The quantity of alcoholic beverages consumed in the heavily damaged areas as well as throughout the prefecture decreased from the 1994 pre-disaster level, both immediately after the Great Hanshin Earthquake (January-March 1995) and 2 years after the disaster. This finding remained once possible confounding factors were taken into consideration. CONCLUSIONS: More attention should be placed on drinking in the cultural context where a disaster occurs. It may sometimes deter, rather than encourage, drinking among the affected population.

Alcohol Drinking↗

Diagnostic value of prostate-specific antigen-related parameters in discriminating prostate cancer.

BACKGROUND: Using the percentage (of total) of free prostate-specific antigen (PSA) in discriminating prostate cancer (CaP) from benign prostate hyperplasia (BPH) has not been fully delineated in Japanese men. To clarify the clinical significance of percent free PSA, various parameters, including total prostate volume, percent free PSA, PSA density (PSAD) and PSA density of transition zone volume (PSAT), were compared. METHODS: Ninety-seven patients who had visited one of three community-based hospitals, and whose total PSA value ranged from 4 to 20 ng/mL were prospectively enrolled in this study. Fresh sera were applied to measure the percent free PSA. RESULTS: Of the 97 patients, CaP and BPH were diagnosed in 24 (25%) and 73 patients, respectively. In discriminating CaP patients, the cutoff values of 17% for percent free PSA, 0.3 ng/mL per cm3 for PSAT, and 0.19 ng/mL per cm3 for PSAD yielded specificity levels of 56, 40 and 58% at sensitivity levels of 92, 92 and 79%, respectively. As for the 65 patients with intermediate PSA, range 410 ng/mL, and normal digital rectal examination, the percent free PSA and total prostate volume statistically discriminated CaP patients from BPH patients. A multiple logistic regression model proved percent free PSA to be the only significant discriminating factor (P=0.045; odds ratio, 9.06). CONCLUSIONS: This prospective study revealed percent free PSA to be a significant useful predictor in discriminating CaP from BPH in Japanese men.

Aged↗

Development of NMDA and non-NMDA receptor-mediated excitatory synaptic transmission in geniculocortical and corticocortical connections in organotypic coculture preparations.

Development of N-methyl-D-aspartate (NMDA) and non-NMDA receptor-mediated excitatory synaptic transmission was studied in the visual cortex using organotypic slice cocultures. A slice of visual cortex (VC) dissected from newborn rats was cocultured with either a chunk of embryonic lateral geniculate nucleus (LGN) or another VC. During 7-38 days in vitro (DIV), geniculocortical monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded from layer IV neurons in response to stimulation of the LGN in cocultures of the VC with the LGN. Similarly, corticocortical monosynaptic EPSPs were recorded from layers II/III and V/VI neurons in cocultures of two VCs when stimulating the partner VC. The initial slopes of the non-NMDA and NMDA receptor-mediated components of the EPSPs, which were dissociated pharmacologically, were assessed and compared among three different culture stages, early (7-11 DIV), middle (12-15 DIV) and late (17-38 DIV). With progression of the culture stage, the non-NMDA component tended to increase in both the geniculocortical and corticocortical connections. In contrast, the NMDA component exhibited distinct developmental changes. The NMDA component in layer IV neurons, which receive geniculate inputs, showed a transient increase in the middle stage. In the corticocortical connection, the magnitude of the NMDA component was large in the early stage and maintained through all culture stages in layer V/VI cells, whereas in layer II/III cells it decreased sharply by the late stage. Our results suggest that glutamatergic transmission in the visual cortex develops differently in the geniculocortical and corticocortical connections.

2-Amino-5-phosphonovalerate↗

Bacillus Calmette-Guérin instillation treatment for carcinoma in situ of the upper urinary tract.

OBJECTIVE: To analyse the efficacy and safety of bacillus Calmette-Guérin (BCG) perfusion treatment forcarcinoma in situ (CIS) of the upper urinary tract. PATIENTS AND METHODS: Six patients with cytologically diagnosed CIS of the upper urinary tract were treated by BCG instillation via retrograde catheterization using a 6 F ureteric catheter or an 8 F indwelling JJ ureteric stent between the ureter and bladder. BCG (Tokyo 172 strain, 80 mg in 100 mL normal saline) was instilled weekly for 4 or 8 weeks. The efficacy and safety of the treatment was assessed. RESULTS: The mean (range) follow-up was 22 (9-38) months; none of the patients died, and all were negative for cytology in urine collected from the upper urinary tracts. However, one patient had recurrent CIS in the prostatic urethra; the patient was treated by intravesical BCG instillation. In all patients, positive cytology became negative after one or two instillations of BCG. The ureter became stenotic in two patients. Although irritative symptoms occurred in all patients, such side-effects disappeared in a few months and were not clinically significant. CONCLUSION: In these six patients retrograde BCG instillation for CIS of the upper urinary tract was effective and safe. Based on the cytology results after only two BCG treatments, the dose or number of BCG instillations could possibly be reduced, but further study is needed.

Adjuvants, Immunologic↗

Clinicopathologic evaluation of hepatocellular carcinoma with bile duct thrombi.

BACKGROUND: The aim of this study was to evaluate the clinicopathologic characteristics of patients with hepatocellular carcinoma (HCC) and bile duct thrombi (BDT). PATIENTS: Seventeen patients with HCC and BDT among 671 patients with HCC who underwent hepatic resection were enrolled in this study. RESULTS: There were no significant differences in the survival rates between patients with and those without BDT, although the rate of stage IV or portal vein invasion was significantly higher in patients with HCC and BDT than in those with HCC but without BDT. In 9 of 17 patients with BDT, preoperative jaundice was observed. Five of the 17 patients underwent a bile duct resection combined with hepatic resection, and 12 patients underwent hepatic resection with removal of the BDT without bile duct resection. None of the patients had histopathologic evidence of direct tumor invasion into the bile duct wall or of any tumor recurrence related to the BDT. There were no significant differences in the survival rates between patients who underwent bile duct resection and those who did not. CONCLUSION: Hepatic resection and the removal of BDT without bile duct resection were sufficient surgical interventions to treat patients with HCC and BDT.

Adult↗

Plasma platelet-activating factor acetylhydrolase deficiency is associated with atherosclerotic occlusive disease in japan.

PURPOSE: Plasma platelet-activating factor acetylhydrolase (PAF-AH) is known to catalyze platelet-activating factor, thereby inactivating its inflammatory function. Deficiency of this enzyme is caused by a missense (G(994)-->T) in exon 9 of the plasma PAF-AH gene. In this study, we investigated a possible association of this mutation with the risk of atherosclerotic occlusive disease (AO) in Japanese patients. METHODS: We studied 104 patients with AO. The control group consisted of 114 subjects matched for age and sex. Plasma PAF-AH activity was measured in the patients with AO. RESULTS: The prevalence of the mutant genotype (GT + TT ) was significantly more frequent in patients with AO than in control subjects (36.5% vs 23.7%; P <.05). Among the patients with AO, those with the mutant allele had significantly more risk factors of prior stroke or ischemic heart disease than patients with normal genotypes. Plasma PAF-AH activity was higher in patients with AO than in control subjects in normal genotype subgroups. CONCLUSIONS: The missense (G(994)-->T) in exon 9 of the plasma PAF-AH gene is associated with AO in Japanese people.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Photosynthesis, plant growth and N allocation in transgenic rice plants with decreased Rubisco under CO2 enrichment.

Ribulose-1,5-bisphosphate carboxylase (Rubisco) efficiency for CO2-saturated photosynthesis was examined in leaves of rice (Oryza sativa L.). The amount of Rubisco in a leaf was calculated to be 30-55% in excess for the light-saturated rate of photosynthesis at 100 Pa CO2. Long-term exposure to CO2 enrichment decreased the amount of Rubisco protein. However, N was not reallocated from decreased Rubisco to other components limiting photosynthesis, and the decrease in Rubisco was simply due to a decrease in total leaf-N content by CO2 enrichment. Thus, rice plants did not optimize N allocation into Rubisco at elevated CO2. Transgenic rice plants with decreased Rubisco were obtained by transformation with the rbcS antisense gene. The transformant with 65% wild-type Rubisco was selected as a plant with optimal Rubisco content for CO2-saturated photosynthesis at the level of a single leaf. This selected transgenic plant had 20% lower rates of photosynthesis at normal CO2 (36 Pa), but 5-15% higher rates of photosynthesis at elevated CO2 (100 Pa) for a given leaf N content. However, such transgenic plants did not necessarily show greater production of biomass even under conditions of CO2 enrichment. Although they had a higher N-use efficiency for plant growth under such conditions during the middle stage of growth, the growth rate was lower during the early stage of growth. Thus, improvement of N-use efficiency by a single leaf did not necessarily lead to greater production of biomass by the whole plant.

Carbon Dioxide↗

Bacterial meningitis observed in a phase I trial of vinorelbine, cisplatin and thoracic radiotherapy for non-small cell lung cancer: report of a case and discussion on dose-limiting toxicity.

Although neutropenia increases the risk of life-threatening infections, bacterial meningitis is rarely encountered as a complication during cancer chemotherapy in adults with a solid tumor. A 66-year-old male with adenosquamous carcinoma of the lung, cT2N3M0, stage IIIB, was enrolled in a phase I trial of chemoradiotherapy and treated with cisplatin 80 mg/m2 (122 mg/ body) on day 1, vinorelbine 20 mg/m2 (32 mg/body) on days 1 and 8 and thoracic radiotherapy 30 Gy/15 fractions, beginning on day 2, with dexamethasone administered for antiemesis at a dose of 16 mg on day 1, 8 mg on days 2 and 3, 4 mg on day 4 and 2 mg on day 5. The patient developed headache and fever on day 6 of the second cycle of the treatment and bacterial meningitis was diagnosed based on the findings of consciousness disturbance, an elevated peripheral blood leukocyte count and numerous leukocytes in the cerebrospinal fluid. In spite of the doctor's delay in establishing the exact diagnosis, the bacterial meningitis in this case was successfully treated with intensive antibiotic therapy. This life-threatening complication, equivalent to a grade 4 non-hematological adverse reaction, was not counted as dose-limiting toxicity in the current phase I trial, because there are only a few reports of bacterial meningitis associated with cancer chemotherapy and it developed in this case without any associated decrease in the peripheral blood leukocyte count.

Aged↗

NMR analysis of intra- and inter-molecular stems in the dimerization initiation site of the HIV-1 genome.

Two positive-strand HIV-1 genomic RNAs form a dimer in virion particles through interaction of the dimerization initiation sites (DIS). The DIS RNA fragment spontaneously formed a "loose-dimer" and was converted into a "tight-dimer" by supplementation with nucleocapsid protein NCp7. This two-step dimerization reaction requires the whole DIS sequence [Takahashi et al. (2000) RNA 6, 96-102]. In the present study, we measured imino proton resonances to investigate the secondary structures of the two types of dimers in a 39-mer RNA covering the entire DIS (DIS39), including discrimination between intra- and inter-molecular base pairing. Both the presence and absence of inter-molecular NOE between (15)N-labeled and unlabeled DIS39 were unambiguously detected in an equimolar mixture of (15)N-labeled and unlabeled DIS39. The stem-bulge-stem structures in both dimers were confirmed and found to be very close to each other from clear superimposition of the NMR spectra in the two dimeric states. Nevertheless, the modes of base pairing in the stems of the loose- and tight-dimers were intra- and inter-molecular, respectively. Our results suggest a large structural alteration of genomic RNA occurs during virion maturation.

Dimerization↗

Making of a facial perforator map by thermography.

It has been confirmed that thermography is an effective method by which to locate perforators to be used for local flaps. One disadvantage of thermography is its complicated procedure. If it was possible to identify perforators quickly and easily, many operations would be dramatically simplified. The authors' objective was to develop a method of mapping surface perforators using thermography. They pressed a vinyl bag filled with ice water against a test area for 25 seconds and began photographing the area directly after icing. Almost all of the enhanced hot spots appeared for 65 seconds after icing. The number and locations of enhanced perforating vessels varied widely, which they anticipated as a result of differences among individuals, and fluctuations in the measuring environment and the performance of measuring instruments. However, the presence of many perforators is common, and these images are considered to be reliable. Based on their findings, the authors consider the facial perforator map to be accurate and useful. Application of the facial perforator map may simplify many operations and may contribute to making surgery safer and more effective.

Adult↗

Congenital synostosis of the fourth and fifth metacarpals treated by free bone grafting from the fusion site.

Simultaneous correction of the alignment and the shortening of the deformed little finger in congenital synostosis of the fourth and fifth metacarpals was accomplished by insertion of a wedge-shaped bone block harvested from the fusion site following transverse osteotomy of the fifth metacarpal. Correction can be performed simply and successfully without morbidity of the donor site when this technique is applied to suitable patients.

Bone Transplantation↗

Monoclonal antibody against Mycoplasma fermentans-specific aminoglycoglycerolipid.

Previously, we reported that Mycoplasma fermentans has specific antigens (phosphocholine-containing glycoglycerolipids: GGPL-I and GGPL-III) and discussed the possibility of their pathogenic role. In this paper, we report the characterization of a monoclonal antibody (MF-III-1) specific to GGPL-III (phosphocholine-containing aminoglycoglycerolipid) using methods of electron microscopy, immunofluorescence cell surface staining, laser scanning microscopy, immunoelectron microscopy, and thin-layer chromatography immunostaining. The MF-III-1 antibody specifically recognized M. fermentans attached to the surface of HTLV-I-infected human helper T-cells, and it did not cross-react with other lipids nor with human T-cell antigens. Since MF-III-1 distinguishes GGPL-III from GGPL-I, the binding site may include a serinol (2-amino-1,3-propanediol) residue of GGPL-III. MF-III-1 is useful for the in vitro study of M. fermentans, and may also be useful as a tool for the study of the involvement of M. fermentans in human diseases.

Animals↗

Adenovirus-mediated gene transduction of IkappaB or IkappaB plus Bax gene drastically enhances tumor necrosis factor (TNF)-induced apoptosis in human gliomas.

Tumor necrosis factor-alpha (TNF), which was initially supposed to be a promising cancer therapeutic reagent, does not kill most types of cancer cells partly due to the activation of an anti-apoptotic gene, NF-kappaB. NF-kappaB forms an inactive complex with the inhibitor kappa B alpha (IkappaBalpha), which is rapidly phosphorylated and degraded in response to various extracellular signals. To disrupt this protective mechanism, we introduced an inhibitor kappa B alpha (IkappaBdN) gene, a deletion mutant gene lacking the nucleotides for the N-terminal 36 amino acids of IkappaBalpha, into human glioma cells (U251, T-98G, and U-373MG) via an adenoviral (Adv) vector in addition to treatment of the glioma cells with recombinant TNF. Immunohistochemical analysis revealed that NF-kappaB was translocated to nuclei by TNF treatment in U251 and T-98G cells, but not in U-373MG cells. Neither transduction of IkappaBdN nor treatment with TNF protein alone induced apoptosis in U251 and T-98G cells, whereas both cell lines underwent drastic TNF-induced apoptosis after transduction of IkappaBdN. On the other hand, U-373MG cells were refractory to TNF-induced apoptosis even when they were transduced with the IkappaBdN gene. U-373MG cells underwent drastically increased apoptosis when co-transduced with the IkappaBdN and Bax gene in the presence of TNF. Adv-mediated transfer of IkappaBdN or IkappaBdN plus Bax may be a promising therapeutic approach to treat gliomas through TNF-mediated apoptosis.

Adenoviridae↗

Adenovirus-mediated transfer of Fas ligand gene augments radiation-induced apoptosis in U-373MG glioma cells.

Most malignant astrocytomas (gliomas) express a high level of Fas, whereas the surrounding normal tissues such as neurons and astrocytes express a very low level of Fas. Thus, transduction of Fas ligand would selectively kill malignant astrocytoma cells. On the other hand, glioma cells harboring p53 mutation have been reported to be resistant to conventional therapies including radiation. To override the resistance mechanism of glioma cells with p53 mutation to radiation, we transduced U-373MG malignant astrocytoma (glioma) cells harboring mutant p53 with Fas ligand via an adenovirus (Adv) vector in combination with X-ray irradiation, and evaluated the degree of apoptosis. The degree of apoptosis in U-373MG cells infected with the Adv for Fas ligand (Adv-FL) and treated with irradiation (81%) was much higher than that in U-373MG cells infected with Adv-FL and not treated with irradiation (0.8%) or that in U-373MG cells infected with the control Adv for lacZ and treated with irradiation (5.0%). In U-373MG cells infected with Adv-FL, irradiation increased the expression of Fas ligand. Coincident with the increase in Fas ligand, there was a marked reduction in the caspase-3 level and a marked increase in the cleaved form of poly(ADP-ribose) polymerase (PARP), which are downstream components of Fas ligand-mediated apoptosis. This suggests that the enhanced activation of caspase-3 by the transduction of Fas ligand combined with irradiation, induced extensive apoptosis in U-373MG cells. In summary, transduction of Fas ligand may override the resistance mechanism to radiotherapy in glioma cells harboring p53 mutation.

Adenoviridae↗