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Biomedical subjects

N Yamashita

Publications and source records attributed to N Yamashita.

At least 19 recordsLinked to original sources

Gaseous adsorption properties of a silica-pillared layered manganese oxide.

Adsorptions of N(2), H(2)O, and organic vapors including CH(2)Cl(2), CCl(4), c-C(6)H(12), C(6)H(6), n-C(6)H(14), and n-C(9)H(20) on a silica-pillared layered manganese oxide (SiHMnO) and nonane-preadsorbed SiHMnO were examined. It is found that SiHMnO has a microporosity with a wide pore width distribution showing different pore wall affinities. Micropores with smaller width preferentially accommodate the nonane preadsorbate while the surface hydrophilicity of pore wall leads to an easier detachment of the adsorbed nonane molecules. H(2)O adsorption influences both the porosity and the surface properties by accelerating a sufficient hydrolysis of the remained TEOS molecules in SiHMnO. Examinations using Dubinin-Radeshkevich (DR) equation and isosteric heat of adsorption of organic molecules provide evidences that the wall surface of micropores with smaller and larger width have less affinity toward nonpolar and polar organic vapors, respectively.

Journal Article↗

Concentrations and fluxes of chloronaphthalenes in sediment from Lake Kitaura in Japan in past 15 centuries.

The concentrations of 63 congeners of chloronaphthalene (CN; polychlorinated naphthalenes, PCNs) in dated on approximately 500 B.C. to 2000 sediment core from the Lake Kitaura in Japan have been quantified by HRGC/HRMS after double column HPLC fractionation. Sediment from the Lake Kitaura showed a time-dependent pattern in distribution of CNs since the approximately 500 B.C. Starting from the 1910s the total CNs content increased accelerating from the 1960s, and, in parallel, the pattern of CN congeners has changed with a substantial increase in contribution from the penta, hexa, hepta, and octaCN. The total CNs content normalized to dry weight of sediment peaked out in the layer dated on 1984-1985, and next nearly two-fold decreased with further gradually decreasing concentration in 1987-2000. An occurrence of tri and tetraCNs in deep sediment layers corresponded to preindustrial synthesis and use of CNs seems to be connected to relatively greater water solubility and mobility in the pore water of those CN homologue groups. Based on CN congener pattern and results of multivariate analysis three main layers were separated in the sediment core. Starting from 1981 the emission sources related to combustion marker congeners become substantial contributors to flux of annually deposited CNs, while relative significance of the evaporative source marker congeners decreased after 1985. The annual flux of CNs into sediments of the Lake Kitaura was 0.073-0.31 pg/cm2 before 1926, increased to 5.5-14 pg/cm2 in 1963-1970 and next sharply increased to 50-107 pg/ cm2 in 1971-1985, and after that decreased to 17 pg/cm2 in 1997-2000.

Chlorine Compounds↗

Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells.

Prostaglandin (PG) E(2) is a known bone absorbing agent that acts on osteoblasts to facilitate osteoclastogenesis by increasing the secretion of RANKL. In the present study, we investigated the direct action of PGE(2) on osteoclastic progenitors that differentiate into TRAP-positive multinucleated cells. The hematopoietic stem cell obtained from murine bone marrow was purified by a Sephadex G-10 column, and cultured in the presence of CSF-1 and RANKL to facilitate cell differentiation. The introduction of low-density PGE(2) into the culture resulted in a drastic increase of TRAP-positive multinucleated cells, whereas the addition of high-density PGE(2) had the opposite effect. PCR analysis revealed increased level of EP3 mRNA in undifferentiated cells and reduced level after the development of osteoclast; EP1, EP2 and EP4 were constitutively expressed throughout the differentiation. Investigation of intracellular signaling verified that low-density PGE(2) suppressed PKA activity in undifferentiated cells, suggesting that PGE(2) acts on the osteoclastic cell lineage to facilitate cell differentiation by suppressing PKA in the presence of RANKL.

Animals↗

Unrelated bone marrow transplantation for Epstein-Barr virus-associated T/NK-cell lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders, including chronic active EBV infection, EBV-associated hemophagocytic syndrome, hypersensitivity to mosquito bites, hydroa vacciniforme, aggressive NK-cell leukemia, and nasal/nasal-type NK-cell lymphoma. In most instances, these disorders are refractory to conventional treatments and have a poor prognosis. Here, we report a new treatment strategy for EBV-associated T/NK-cell LPD, consisting of immunochemotherapy, intensive combination chemotherapy, and stem cell transplantation. The five patients studied, two with T-cell and three with NK-cell LPD, lacked a human leukocyte antigen-matched, related donor, and therefore received bone marrow grafts from HLA-matched, unrelated donors. The preconditioning regimen consisted of total-body irradiation (12 Gy), etoposide (900 mg/m(2)), and cyclophosphamide (120 mg/kg) or melphalan (210 mg/m(2)). All patients had residual LPD by a quantitative PCR technique prior to transplantation. After unrelated bone marrow transplantation (UBMT), four of the five patients remain in continuous complete remission at a median of 19 months, without detectable EBV-DNA in peripheral blood. Thus, UBMT appears to be a reasonable option for the treatment of patients with EBV-associated T/NK-cell LPD. Detection of EBV-DNA by PCR offers an important tool for assessing minimal residual disease in patients with EBV-associated T/NK-cell LPD.

Adolescent↗

Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia of the M0 subtype.

Point mutations of the transcription factor AML1 are associated with leukemogenesis in acute myeloblastic leukemia (AML). Internal tandem duplications (ITDs) in the juxtamembrane domain and mutations in the second tyrosine kinase domain of the Fms-like tyrosine kinase 3 (FLT3) gene represent the most frequent genetic alterations in AML. However, such mutations per se appear to be insufficient for leukemic transformation. To evaluate whether both AML1 and FLT3 mutations contribute to leukemogenesis, we analyzed mutations of these genes in AML M0 subtype in whom AML1 mutations were predominantly observed. Of 51 patients, eight showed a mutation in the Runt domain of the AML1 gene: one heterozygous missense mutation with normal function, five heterozygous frameshift mutations and two biallelic nonsense or frameshift mutations, resulting in haploinsufficiency or complete loss of the AML1 activities. On the other hand, a total of 10 of 49 patients examined had the FLT3 mutation. We detected the FLT3 mutation in five of eight (63%) patients with AML1 mutation, whereas five of 41 (12%) without AML1 mutation showed the FLT3 mutation (P=0.0055). These observations suggest that reduced AML1 activities predispose cells to the acquisition of the activating FLT3 mutation as a secondary event leading to full transformation in AML M0.

Cell Transformation, Neoplastic↗

Polychlorinated naphthalene contamination of some recently manufactured industrial products and commercial goods in Japan.

A follow-up case study was performed after two incidents of recent illegal import and use in Japan both of technical PCNs mixture and contaminated with those compounds an industrial raw material. In case 1, above 18 tons of PCNs mixture, resembling Halowax 1001, which is a technical PCNs formulation, were imported from the United Kingdom. An illegally imported PCNs mixture was used for manufacture of a wide spectrum of industrial materials and commercial goods including sealants, putty, shock absorbing materials, adhesive materials, insulating materials and rubber belts. About 1.3 tons of PCNs contained in the Neoprene FB manufactured reached domestic market and 9.3 tons could reach other markets. In case 2, which became known in 2001, the Japanese company imported from Canada 54 tons of PCNs contaminated raw rubber material for industrial use. In weathering test (40 degrees C for up to 168 h) of the feral rubber coated sheets for rubber bands 98% of di- and 66% of tri-CNs vaporized. A loss rate of tetra-, penta-, and hexa-CN during initial 12 h of the weathering test ranged from approximately 10 to approximately 20%, while from 12 to 168 h remained negligible.

Chlorine Compounds↗

Content of reticulocyte hemoglobin is a reliable tool for determining iron deficiency in dialysis patients.

BACKGROUND: The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin (rHuEPO) treatment. Iron status of the patients can be determined from the recently available measurement of content of reticulocyte hemoglobin (CHr). METHODS: In this study, to clarify the accuracy of CHr in diagnosing iron deficiency in hemodialysis (HD) patients, we initially compared CHr with such conventional iron parameters as serum ferritin levels, transferrin saturation and serum soluble transferrin receptor levels. Secondly, we investigated the changes in CHr during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 149 hemodialysis (HD) patients and 53 age-matched healthy subjects. Iron deficiency was defined as having a TSAT of less than 20% and serum ferritin of less than 100 ng/ml. Conventional parameters of red blood cells and CHr were measured by an ADVIA120 autoanalyzer. RESULTS: Mean CHr was 32.3 +/- 2.2 pg in the patients undergoing hemodialysis treatment. CHr significantly correlated with iron parameters in the dialysis patients. Logistic regression analysis was performed to determine the relationship between CHr and each outcome measure, and CHr was the significant multivariate predictor of iron deficiency. Iron supplements given to the patients with low CHr and hematocrit (Hct) significantly increased Hct, resulting in a decrease in the weekly dosage of rHuEPO. CONCLUSIONS: CHr, measured simultaneously with Hct, is a sensitive and specific marker of iron status in dialysis patients.

Adult↗

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.

We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 x 10(7)/kg recipient body weight) were transplanted to an 8-10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte gamma-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 x 10(9)/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 x 10(9)/l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.

Adult↗

Lung herniation as an anatomic consequence of pneumonectomy.

BACKGROUND: Pneumonectomy causes an overdistention of the remaining lung as an adaptive response. Excessive lung herniation occasionally causes serious lung dysfunction. METHODS: Twenty-seven patients were selected from 152 patients who underwent pneumonectomy for lung cancer between 1990 and 1998. Complete resections were accomplished; no recurrence was observed for 3 years in these 27 patients. To evaluate the extent of herniation, the Lung Herniation Index (LHI) was developed and defined as the sum of proportions of the maximal transverse length of the remaining lung divided by the transverse length of the thoracic cavity, measured at the level of the aortic arch and the inferior pulmonary vein on chest computed tomography. Sequential changes in LHI were compared between groups. RESULTS: Changes in LHI did not differ between groups delineated on the basis of an FEV1 of 70 % (p = 0.45) and RV/TLC of 40 % (p = 0.99). Patients with a low body mass index (BMI) (< 20 kg/m(2)), however, showed a significantly greater degree of lung herniation than those with a high BMI (> or = 20 kg/m(2)) (p < 0.05). CONCLUSIONS: Concomitant COPD has no effect on lung herniation. Some preventive procedure should be considered for patients with low BMI.

Adult↗

Oxidative DNA damage in cultured cells and rat lungs by carcinogenic nickel compounds.

DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. DNA strand breaks in cultured cells exposed to nickel compounds were measured by using a pulsed field gel electrophoresis technique. Among nickel compounds (Ni(3)S(2), NiO (black), NiO (green), and NiSO(4)), only Ni(3)S(2), which is highly carcinogenic, induced lesions of both double- and single-stranded DNA in cultured human cells (Raji and HeLa cells). Treatment of cultured HeLa cells with Ni(3)S(2) (10 microg/ml) induced a 1.5-fold increase in 8-hydroxy-2'-deoxyguanosine (8-OH-dG) compared with control, whereas NiO (black), NiO (green), and NiSO(4) did not enhance the generation of 8-OH-dG. Intratracheal instillation of Ni(3)S(2), NiO(black), and NiO(green) to Wistar rats increased 8-OH-dG in the lungs significantly. NiSO(4) induced a smaller but significant increase in 8-OH-dG. Histological studies showed that all the nickel compounds used induced inflammation in lungs of the rats. Nitric oxide (NO) generation in phagocytic cells induced by Ni(3)S(2), NiO(black), and NiO(green) was examined using macrophage cell line RAW 264.7 cells. NO generation in RAW 264.7 cells stimulated with lipopolysaccharide was enhanced by all nickel particles. Two mechanisms for nickel-induced oxidative DNA damage have been proposed as follows: all the nickel compounds used induced indirect damage through inflammation, and Ni(3)S(2) also showed direct oxidative DNA damage through H(2)O(2) formation. This double action may explain relatively high carcinogenic risk of Ni(3)S(2).

8-Hydroxy-2'-Deoxyguanosine↗

Catechol estrogens induce oxidative DNA damage and estradiol enhances cell proliferation.

Estrogen-induced carcinogenesis involves enhanced cell proliferation (promotion) and genotoxic effects (initiation). To investigate the contribution of estrogens and their metabolites to tumor initiation, we examined DNA damage induced by estradiol and its metabolites, the catechol estrogens 2-hydroxyestradiol (2-OHE(2)) and 4-hydroxyestradiol (4-OHE(2)). In the presence of Cu(II), catechol estrogens formed piperidine-labile sites at thymine and cytosine residues in (32)P 5'-end-labeled DNA fragments and induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine. NADH markedly enhanced Cu(II)-dependent DNA damage mediated by nanomolar concentrations of catechol estrogens. Catalase and bathocuproine inhibited the DNA damage, suggesting the involvement of H(2)O(2) and Cu(I). These results suggest that H(2)O(2), generated during Cu(II)-catalyzed autoxidation of catechol estrogens, reacts with Cu(I) to form the Cu(I)-peroxide complex, leading to oxidative DNA damage, and that NADH enhanced DNA damage through the formation of redox cycle. To investigate the role of estrogens and their metabolites in tumor promotion, we examined their effects on proliferation of estrogen-dependent MCF-7 cells. Estradiol enhanced the proliferation of MCF-7 cells at much lower concentrations than catechol estrogens. These findings indicate that catechol estrogens play a role in tumor initiation through oxidative DNA damage, whereas estrogens themselves induce tumor promotion and/or progression by enhancing cell proliferation in estrogen-induced carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Molecular detection of metastatic retinoblastoma cells by reverse transcription polymerase reaction for interphotoreceptor retinoid-binding protein mRNA.

BACKGROUND: In the current study, the authors report a 4 year old girl with disseminated retinoblastoma. To find sensitive and specific molecular markers for detection of retinoblastoma cells in blood and marrow, the authors evaluated three photoreceptor-associated gene transcripts by using reverse transcription polymerase chain reaction (RT-PCR). METHOD: Samples of bone marrow and blood were obtained from healthy donors and the patient. RT-PCR was performed to detect the cone alpha'-subunit of cGMP phosphodiesterase (cone alpha'-PDE), the rod beta-subunit of cGMP (rod beta-PDE), and the interphotoreceptor retinoid-binding protein (IRBP) gene transcript in RNA extracted from the samples. RESULTS: While no expression of rod beta-PDE or IRBP was detected in any of the normal samples, expression of cone alpha'-PDE was detected in two out of seven normal marrow samples. Expression of rod beta-PDE was not detected in the patient samples. Expression of IRBP was detected in the patient samples obtained from iliac bone marrow before intensive chemotherapy but not thereafter. CONCLUSION: RT-PCR for IRBP was a useful method for detecting metastatic retinoblastoma cells as well as for evaluating the therapeutic effects of treatment in this particular case.

Antineoplastic Combined Chemotherapy Protocols↗

Polychlorinated naphthalenes, -biphenyls, -dibenzo-p-dioxins, and -dibenzofurans in double-crested cormorants and herring gulls from Michigan waters of the Great Lakes.

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), naphthalenes (PCNs), and biphenyls (PCBs) were measured in eggs of double-crested cormorants and herring gulls collected from Michigan waters of the Great Lakes. Concentrations of PCNs in eggs of double-crested cormorants and herring gulls were in the ranges of 380-2400 and 83-1300 pg/g, wet wt, respectively. Concentrations of 2,3,7,8-substituted PCDDs and PCDFs were 10-200 times less than those of PCNs in eggs whereas those of total PCBs (380-7900 ng/g, wet wt) were 3-4 orders of magnitude greater. While the profile of PCB isomers and congeners between double-crested cormorants and herring gulls was similar, the PCN isomer profile differed markedly between these two species. PCN congeners 66/67 (1,2,3,4,6,7/1,2,3,5,6,7) accounted for greater than 90% of the total PCN concentrations in herring gulls, whereas their contribution to total PCN concentrations in double-crested cormorants ranged from 18 to 40% (mean, 31%). The ratios of concentrations of PCDDs to PCDFs were greater in herring gulls than in double-crested cormorants collected from the same locations, suggesting the ability of the former to metabolize PCDF congeners relatively rapidly. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs) contributed by PCNs in double-crested cormorant and herring gull eggs were 2-3% of the sum TEQs of PCBs, PCDDs, PCDFs, and PCNs. PCB congener 126 (3,3',4,4',5-PeCB) accounted for 57-72% of the total TEQs in double-crested cormorant and herring gull eggs.

Animals↗

Hereditary angioedema with a de novo mutation of exon 8 in the C1 inhibitor gene showing recurrent edema of the hands around the peripheral joints: importance for the differential diagnosis of joint swelling.

We describe a patient with hereditary angioedema (HAE), showing recurrent edema around the peripheral joints. Her symptoms began at the age of 18 with hand swelling distal to the wrist joints. Until she was referred to our hospital 3 years after her initial symptoms, she was still undiagnosed, although she was suspected of having rheumatoid arthritis. Laboratory examination showed reduced levels of CH50 and C4 with normal C3 levels. The C1 inhibitor (C1-INH) was decreased to 5 mg/ml, with remarkably reduced activity. Although these findings were compatible with a diagnosis of HAE, there were no episodes of skin edema in her family. To establish the diagnosis, we carried out DNA analysis of the C1-INH gene, which revealed a newly identified de novo mutation of G to A at nucleotide 16869 in exon 8. As described in this patient, localized edema around the peripheral joints may be the only manifestation of HAE. HAE should therefore be taken into consideration for the differential diagnosis of joint swelling.

Adolescent↗

Glucocorticoid-regulated expression of exogenous human growth hormone gene in rats.

The aim of this study was to control in vitro and in vivo expression of the growth hormone (GH) gene using a glucocorticoid-sensitive promoter, the mouse mammary tumor virus long terminal repeat (MMTV LTR). We inserted the cDNA encoding the 20-kDa form of human GH (20K-GH) downstream of the MMTV LTR of plasmid pMSG, and used lipofection to transfer it to 3Y1 cells together with plasmid pMX, which contains a puromycin-resistant element. The secretion of GH from the selected transformants was dose-dependently augmented by the application of hydrocortisone, corticosterone, or dexamethasone, among which dexamethasone was the most potent. Analysis of the time course showed that 20K-GH secretion began to increase within 2 hours after the addition of glucocorticoid and reached a maximal level of about threefold over the unstimulated control at 3 hours; secretion then gradually declined and returned to near basal levels at 19 hours. Repeated glucocorticoid application led to repeated increases in GH secretion. When GH-producing cells were microcapsulated and transplanted into the abdominal cavities of rats, 20K-GH was detected in the plasma under control conditions and increased about 3.3-fold after administration of dexamethasone. We suggest that GH expression driven by the MMTV LTR promoter may be under the control of an endogenous glucocorticoid in vivo.

Animals↗

An amebic lung abscess: report of a case.

Recently the number of amebiasis cases has increased in Japan. Pleuropulmonary amebiasis is a very rare complication of liver amebiasis. We report herein the case of a 54-year-old man presenting with an amebic lung abscess in his right lower lung. The diagnosis of lung amebiasis was established from a direct examination of the pus in which trophozoites of Entamoeba histolytica were detected. After the oral administration of metronidazole, the laboratory findings improved and he thus underwent a right lower lobectomy. He was discharged without any relapse of infection 20 days after a thoracotomy. We conclude that a protozoan infection should thus be suspected in the case of a pleuropulmonary infection in which several types of antibiotics prove to be ineffective.

Amebiasis↗

Surgical treatment of chronic subdural hematoma based on intrahematomal membrane structure on MRI.

BACKGROUND: To determine the optimal surgical management of chronic subdural hematoma (CSDH), we assessed which operative procedure, burr holes or small craniotomy, was more effective on 49 consecutive patients. METHOD: We retrospectively classified all cases into two groups according to the intrahematomal membrane structure of CSDH on T2*-weighted magnetic resonance (MR) imaging. The first group, labeled type B, included hematomas which had no intrahematomal membrane and/or were monolayer multilobule. The second group, labeled type C, consisted of hematomas which were divided into multiple layers by the intrahematomal membrane. FINDINGS: The outcome of type C patients treated with burr holes was significantly inferior to that of those who underwent a small craniotomy in terms of the relative outcome of neurological grading. re-operation ratio, and postoperative hospital stay (p < 0.05). Type C hematomas treated with burr holes also had inferior outcome compared with a small craniotomy in terms of the duration of hematoma until disappearance on postoperative CT (p < 0.05). INTERPRETATION: We concluded that a considerable number of cases appeared to need craniotomy and resection of intrahematomal membrane for complete recovery in CSDH, and that T2*-weighted MR imaging could be used as a basis for selecting the operative procedure for CSDH.

Adult↗

High-resolution scanning electron microscopic evaluation of cell-membrane porosity by ultrasound.

The effect of low-intensity ultrasound on HL-60 cells (human promyelocytic leukemia cells) in the presence of the photo sensitizing drug merocyanine 540 (MC 540) was evaluated morphologically, using a high-resolution scanning electron microscope and a transmission electron microscope. Exposure of HL-60 cells to ultrasound without MC 540 resulted in a decrease of finger-like processes in the cells. The cells showed many undulating ruffles on the surface. Distinct pits or holes in the membrane were not observed in these cells. The surface of HL-60 cells treated only with MC 540 was relatively smooth compared with that of control cells. HL-60 cells exposed to ultrasound in the presence of MC 540 showed apparent surface deformation. Numerous crater-like depressions of heterogeneous dimensions were observed in many cells. In addition, various-sized pores were noted in the cell membranes of more damaged cells. These results indicate that cell degeneration was induced by a rapid change in cell membrane porosity during sonication in the presence of MC540.

Apoptosis↗