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Biomedical subjects

N Yamamoto

Publications and source records attributed to N Yamamoto.

At least 37 records · Page 2Linked to original sources

Contrast analysis of dislocation images in TEM-cathodoluminescence technique.

Monochromatic cathodoluminescence CL images of the threading dislocations in Si-doped n-GaN were observed by the TEM-CL technique. We studied dependence of the contrast and the FWHM of the dislocation image on sample thickness, accelerating voltage and temperature. The CL spectra were measured at various temperatures and were analyzed to find the property of the band edge (BE) emission used for the CL imaging. The observation showed that the FWHM of the dislocation contrast monotonically increases with sample thickness and decreases with accelerating voltage, which qualitatively agrees with the behavior expected from the theory. On the other hand, the temperature dependence of the FWHM shows an anomalous behavior. This dependence can be explained by the mobility and lifetime of holes as a function of temperature. The relation between the FWHM of the dislocation contrast and the diffusion length is also discussed.

Journal Article↗

Decline of anti-desmoglein 1 IgG ELISA scores by withdrawal of D-penicillamine in drug-induced pemphigus foliaceus.

A case of pemphigus foliaceus arising during the administration of D-penicillamine was reported. A 72-year-old woman with systemic sclerosis developed flaccid vesicles and crusted erythema of the skin after administration of D-penicillamine for 1-year. She was positive for anti-desmoglein 1 IgG by ELISA. The withdrawal of D-penicillamine resulted in improvement of the skin lesions and ELISA scores for anti-demoglein 1 antibodies revealed a surprisingly rapid decline. This case is a classical incidence of drug-induced pemphigus foliaceus, in which D-penicillamine was constantly required not only to induce, but also to maintain the production of the autoantibodies.

Aged↗

A novel exopolysaccharide from a clinical isolate of Prevotella nigrescens: purification, chemical characterization and possible role in modifying human leukocyte phagocytosis.

Prevotella nigrescens, a gram-negative black-pigmented anaerobic rod, has frequently been isolated from periodontitis and periapical periodontitis lesions. We have isolated an exopolysaccharide-producing P. nigrescens, strain 22, from a chronic periodontitis lesion. The purpose of this study was to determine the chemical composition and function of the exopolysaccharide associated with this clinical isolate. The chemical composition and structure of the purified exopolysaccharide from strain 22 were determined by high performance liquid chromatography and methylation analysis. To define the biological function of this exopolysaccharide, a chemically induced exopolysaccharide nonproducing mutant, strain 328, which was derived from strain 22, was established. The biological effects of exopolysaccharide were determined by comparing the ability of strain 22, strain 328 or heat-killed strain 22 to form abscesses in mice and to interfere with the phagocytic activity of peripheral blood polymorphonuclear leukocytes. Chemical analysis showed that isolated exopolysaccharide consisted of mannose (521.6 microg/mg), glucose (25.6 microg/mg), fructose (65.8 microg/mg), galactose (12.5 microg/mg), arabinose (6.2 microg/mg), xylose (3.2 microg/mg), rhamnose (6.1 microg/mg), and ribose (0.6 microg/mg). Methylation analysis of exopolysaccharide indicated that the linkages of mannose were primarily (1-->2, 1-->6) (1-->2) (1-->6), and (1-->3). Strain 22 and, to a lesser extent, its heat-killed counterpart induced greater abscess formation in mice than strain 328, even though the enzymatic profile of strain 22 was similar to that of strain 328. The ability of strain 328 to induce abscess formation was restored by adding the purified exopolysaccharide isolated from strain 22 to the cell suspension of strain 328. Exopolysaccharide alone failed to induce abscess formation in mice. Further, strain 328 but not the untreated or heat-killed strain 22, was phagocytosed by polymorphonuclear leukocytes both in the presence and in the absence of opsonic factors. The results suggest that these polysaccharides isolated from strain 22, which primarily consisted of mannose, may play a key role in the development of the chronic inflammatory lesion from which this strain was isolated.

Abscess↗

Reconstruction using an autograft containing tumour treated by liquid nitrogen.

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary. The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.

Adolescent↗

Murine synaptosomal lipid raft protein and lipid composition are altered by expression of human apoE 3 and 4 and by increasing age.

Apolipoprotein E (apoE) 4 and aging are risk factors for Alzheimer's disease (AD). Mice expressing human apoE4 and aged wild-type mice show a similarity in the transbilayer distribution of cholesterol in synaptic plasma membranes (SPMs) but differ markedly compared with apoE3 mice and young mice. The largest changes in cholesterol distribution were observed in the SPM exofacial leaflet where there was a doubling of cholesterol. Lipid rafts are thought to be associated with the exofacial leaflet, and we proposed that lipid raft protein and lipid composition would be associated with apoE genotype and age. Lipid rafts were isolated from synaptosomes of different age groups (2, 12, 24 months) of mice expressing human apoE3 and apoE4. Lipid raft markers, alkaline phosphatase (ALP), flotillin-1, cholesterol and sphingomyelin (SM) were examined. Lipid rafts of young apoE4 mice were more similar to older mice as compared with young apoE3 mice in reductions in alkaline phosphatase activity and flotillin-1 abundance. Lipid raft cholesterol and sphingomyelin levels were not significantly different between the young apoE3 and apoE4 mice but cholesterol levels of lipid rafts did increase with age in both genotypes. Results of the present study demonstrate that the two risk factors for Alzheimer's disease, apoE4 genotype and increasing age have similar effects on brain lipid raft protein markers and these findings support the notion that the transbilayer distribution of cholesterol is associated with lipid raft function.

Aging↗

Linkage and association of febrile seizures to the IMPA2 gene on human chromosome 18.

BACKGROUND: Febrile seizures (FSs) are the most common form of childhood seizures, and genetic factors play a role in susceptibility to FS. OBJECTIVE: To identify novel loci and genes associated with susceptibility to FS. METHODS: Study participants were the FS probands and family members of 59 Japanese nuclear families (223 members including 112 affected children). Forty-eight of these families had at least two affected children for which genome-wide linkage screening was carried out. The Genehunter software was used to perform nonparametric multipoint linkage analysis. Mutational and association analyses were conducted in all 59 Japanese FS families. RESULTS: Genotyping data of 407 microsatellite markers suggested linkage of FSs to chromosome 18p11.2 (non-parametric linkage score = 3.68, p = 0.0001). This region includes the IMPA2 gene, which encodes myo-inositol monophosphatase (IMPase) 2. In the phosphatidylinositol-signaling pathway, IMPase is inhibited by lithium, which has a proconvulsant effect, and is stimulated by carbamazepine, an anticonvulsant. A systematic search was performed for mutations in IMPA2 in 24 unrelated randomly selected Japanese FS patients; seven variants were detected. Haplotype analysis revealed an association of a common haplotype in IMPA2 with FSs (p = 0.0009). CONCLUSION: The authors found a novel locus on chromosome 18p11.2 for febrile seizures (FSs). IMPA2 is likely to be an FS susceptibility gene.

Bipolar Disorder↗

Multi-institutional phase II trial of irinotecan, cisplatin, and etoposide for sensitive relapsed small-cell lung cancer.

Irinotecan (CPT-11) has been shown to exhibit excellent antitumour activity against small-cell lung cancer (SCLC). A multi-institutional phase II study was therefore conducted to evaluate the efficacy and toxicity of CPT-11 combined with cisplatin (CDDP) and etoposide (ETOP) (PEI regimen) for the treatment of sensitive relapsed SCLC. Patients who responded to first-line chemotherapy but relapsed more than 8 weeks after the completion of first-line therapy (n=40) were treated using the PEI regimen, which consisted of CDDP (25 mg m(-2)) weekly for 9 weeks, ETOP (60 mg m(-2)) for 3 days on weeks 1, 3, 5, 7, and 9, and CPT-11 (90 mg m(-2)) on weeks 2, 4, 6, and 8 with granulocyte colony-stimulating factor support. Five complete responses and 26 partial responses were observed, and the overall response rate was 78% (95% confidence interval 61.5-89.2%). The median survival time was 11.8 months, and the estimated 1-year survival rate was 49%. Grade 3/4 leucocytopenia, neutropenia, and thrombocytopenia were observed in 55, 73, and 33% of the patients, respectively. Nonhaematological toxicities were mild and transient in all patients. In conclusion, the PEI regimen is considered to be highly active and well tolerated for the treatment of sensitive relapsed SCLC.

Adult↗

Hypoxia-induced nitric oxide protects chondrocytes from damage by hydrogen peroxide.

OBJECTIVE: Because articular cartilage has no vascular supply, chondrocytes are hypoxic under normal physiological conditions. Nitric oxide (NO) plays an important role in chondrocyte damage, such as apoptosis. Although oxygen stress with hydrogen peroxide was found to cause chondrocyte damage, these data were obtained under normoxic (21% O2) conditions. We investigated the effects of hypoxia on hydrogen peroxide-induced chondrocyte damage METHODS: Bovine articular chondrocytes were used in this study. Proteoglycan (PG) synthesis and the induction of apoptosis were analyzed with [(35)S]-sulfate incorporation and annexin V staining, respectively. The induction of NO was examined using a fluorescent probe and RT-PCR. RESULTS: Cells maintained at 5% O2 had the maximum PG synthesis. Under normoxic conditions, hydrogen peroxide inhibited PG synthesis and induced annexin V positive cells in a dose-dependent fashion. However, in those cells cultured under hypoxic (5%) conditions, the hydrogen peroxide-induced annexin V expression was attenuated. Chondrocytes exposed to hypoxia showed induction of NO. When the hypoxia-induced NO was inhibited, the hypoxia-enhanced PG synthesis was abolished and hydrogen peroxide clearly induced cell damage. CONCLUSIONS: Endogenous NO induced by hypoxia protects chondrocytes from apoptosis induced by an oxidative stress.

Animals↗

Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer.

To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with gemcitabine, and to observe their antitumour activity, we conducted a combination phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8, every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC who received no prior chemotherapy or one previous chemotherapy regimen were enrolled. The most frequent toxicities were neutropenia and thrombocytopenia; nonhaematological toxicities were generally mild. Three out of six patients experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine, which was regarded as the MTD. There were three partial responses, for an overall response rate of 16.7%. The median survival time and 1-year survival rate were 9.1 months and 34.1%, respectively. This combination is well tolerated and active for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and further evaluation in prospective randomised trials with cisplatin- or carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.

Adult↗

Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803).

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2) and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8 and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival.

Adult↗

Neurovascular compression of the common peroneal nerve by varicose veins.

Compression of the common peroneal nerve occurs sometimes, but compression caused by varicose veins has not been reported before. We report a case of common peroneal nerve compression syndrome which was confirmed and treated surgically. A 63-year-old woman complained of paraesthesia on the lateral aspect of the right leg, which was worse in the evening. A primary varicose vein arising from non-saphenous tributaries was seen in the posterior calf. Her symptoms resolved with the wearing of compression hosiery for 2 weeks. At operation, the common peroneal nerve was found to be surrounded by tortuous varicosities. After decompression the paraesthesia on the lateral aspect of the right leg resolved completely with no evidence of residual neuralgia.

Female↗

Epitope analysis of the cerebrospinal fluid IgG in HTLV-I associated myelopathy patients using phage display method.

We, for the first time, analyzed the binding motifs of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients with a phage library displaying 12-mer random peptides. As a result, the sequences highly homologous to HTLV-I gp46 192-199, 237-243 and 255-261 were the common linear epitopes of high affinity- IgG exclusively detected in both CSF and sera of the patients. These IgG responses were confirmed with corresponding HTLV-I peptides and serum antibody titers significantly correlated with disease severity or duration. Gp46 237-243 has not been detected in previous enzyme-linked immunosorbent assay (ELISA) studies using bound longer peptides, suggesting the usefulness of the phage display method.

Adult↗

Brain-derived neurotrophic factor induces rapid morphological changes in dendritic spines of olfactory bulb granule cells in cultured slices through the modulation of glutamatergic signaling.

While the acute physiological effects of brain-derived neurotrophic factor (BDNF) have been well demonstrated, little is known regarding possible morphological effects that occur within a short period of time. The acute effects of BDNF on dendritic spine morphology were examined in granule cells in cultured main olfactory bulb slices. Organotypic slices prepared from 7-day-old rats were cultured for 1 day, and BDNF was applied at varying time points prior to fixation. Granule cell dendrites were labeled with a membrane dye and observed with a confocal laser scanning microscope. The addition of BDNF into the culture medium 6 h before fixation decreased the mean diameter of the dendritic processes (filopodia/spines), but the length and density of the processes were not affected. Both filopodia/spines in the external plexiform layer and those in the granule cell layer exhibited similar changes. Considering the slow penetration into the slices, BDNF was then applied to the top of each slice. When applied 1 h before fixation, 5 ng and 0.5 ng of BDNF induced the same changes in the external plexiform layer and the granule cell layer, respectively. The changes became detectable as early as 30 min when 50 ng of BDNF was applied. The pretreatment with tetanus toxin or an N-methyl-D-aspartate receptor antagonist abolished the acute effects of BDNF on spine morphology. These results indicate that BDNF can alter spine morphology within a shorter period of time than previously observed and that the effects are mediated by enhanced glutamatergic signaling.

Animals↗

Decrease of CD154 intensity on peripheral CD4+ T cells in autoimmune thyroid disease.

To clarify immunological differences among patients with Graves' disease (GD) and Hashimoto's disease (HD) at various levels of severity, we examined the expression of the CD154 molecules on peripheral T cells, which regulate B cell activation, B cell differentiation, and T-cell survival. We found decreases in the intensities of CD154 on peripheral CD4(+) cells from euthyroid patients with GD and HD, but we did not find any differences between patients with different disease severities. CD8(+) cells did not express CD154 molecules. Thus, CD154 expression on CD4(+) cells may be related to the pathogenesis of the autoimmune thyroid diseases, not to the disease severity.

Adult↗

Lower concentration of serum soluble CD8 in severe Hashimoto's disease.

To investigate the roles of soluble CD4 (sCD4) and CD8 (sCD8) in the severity of autoimmune thyroid diseases, we examined serum concentrations of sCD4 and sCD8 in various degrees of severity of Hashimoto's disease (HD) and Graves' disease (GD) by enzyme immunoassay. The serum concentration of sCD8 was lower in euthyroid patients with HD undergoing treatment for hypothyroidism (severe HD) than in untreated, euthyroid patients with HD (mild HD), but the sCD4 concentration did not differ between patients with severe and mild HD. The serum sCD8 concentration was negatively correlated with the proportion of CD25(+) cells in CD8(+) cells in patients with severe HD. Serum sCD4 and sCD8 concentrations did not differ between euthyroid patients with GD in remission and those with intractable GD. These results indicate that serum sCD8 is involved in the severity of HD, possibly by down-regulating the function of cytotoxic T cells.

CD4 Antigens↗