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Biomedical subjects

A Nakanishi

Publications and source records attributed to A Nakanishi.

At least 19 recordsLinked to original sources
PubMed2005

Interannual genetic heterogeneity of pollen pools accepted by Quercus salicina individuals.

Since flowering often varies among years in wind-pollinated woody species, the genetic composition of pollen pools accepted by seed parents can differ between years. The interannual heterogeneity of pollen flow may be important for maintaining genetic diversity within populations because it can increase genetic variation within populations and the effective sizes of the populations. In this study we examined heterogeneity, using paternity analysis and analysis of molecular variance, in the genetic composition of pollen pools among different reproductive years for six Quercus salicina seed parents in an 11.56-ha plot in a temperate old-growth evergreen broadleaved forest. The genotypes at seven microsatellite loci were determined for 111 adult trees and 777 offspring of the six seed parents in 2-5 reproductive years. Genetic differentiation of pollen pools among different reproductive years for each seed parent was significant over all seed parents and for each of four seed parents that were analysed for more than 2 years, but not for either of the other two seed parents (analysed for 2 years). For both the pollen pools originating from inside the plot and those originating from outside it, genetic differentiation among different reproductive years for each seed parent was significant over all seed parents. However, among-year genetic differentiation in the pollen pools originating from within the plot was detected for all four of the seed parents that were analysed for more than 2 years, but for only one of the four in the pools originating from outside the plot. Genetic diversity (estimated as allelic richness and gene diversity) was higher for pollen pools over all reproductive years than for pollen pools in single years. These results indicate that the year-to-year genetic variation of pollen pools increases genetic diversity in offspring and is strongly affected by the variation in pollen parents within the plot because of their high pollination contributions. The high year-to-year variation in pollen parents within the plot and overall supports the hypothesis that the offspring produced across years represent a larger genetic neighbourhood.

Analysis of Variance↗
PubMed2002

Discrete change of spin-density-wave modulation in Cr(100)/Sn multilayers as a function of Cr layer thickness.

Magnetic structures of epitaxial Cr(001)/Sn multilayers, where monatomic Sn layers are periodically embedded in a Cr(001) film, were studied using neutron diffraction and Mössbauer spectroscopy. It was found that spin-density-wave (SDW) antiferromagnetic structures with the modulation along the perpendicular direction to the film plane are stabilized at low temperatures. The wavelength of the SDW discretely changes as a function of the superlattice period. The enhanced magnetic moments of Cr at the Cr/Sn interfaces are thought to pin the antimode of the SDW modulation at the interface, resulting in the SDW with the modulation harmonic to the superlattice period.

Journal Article↗
PubMed2001

Soil N fluxes in three contrasting dry tropical forests.

A comparative study of N fluxes in soil among a dry dipterocarp forest (DDF), a dry evergreen forest (DEF), and a hill evergreen forest (HEF) in Thailand was done. N fluxes in soil were estimated using an ion exchange resin core method and a buried bag method. Soil C and N pools were 38 C Mg/ha/30 cm and 2.5 N Mg/ha/30 cm in DDF, 82 C Mg/ha/30 cm and 6.2 N Mg/ha/30 cm in DEF, and 167 C Mg/ha/30 cm and 9.3 N Mg/ha/30 cm in HEF. Low C concentration in the DDF and DEF sites was compensated by high fine soil content. In the highly weathered tropical soil, fine soil content seemed to be important for C accumulation. Temporal and vertical fluctuations of N fluxes were different among the sites. The highest N flux was exhibited at the onset of the wet season in DDF, whereas inorganic N production and estimated uptake of N were relatively stable during the wet season in DEF and HEF. It is suggested that N cycling in soil becomes stable in dry tropical forests to intermediate in temperate forests. N deposition may result in large changes of N cycling in the DDF and DEF due to low accumulations of C and N.

Carbon↗
PubMed2001

Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.

Airway hyperresponsiveness (AHR), goblet cell metaplasia, and mucus overproduction are important features of bronchial asthma. To elucidate the molecular mechanisms behind these pulmonary pathologies, we examined for genes preferentially expressed in the lungs of a murine model of allergic asthma by using suppression subtractive hybridization (SSH). We identified a gene called gob-5 that had a selective expression pattern in the airway epithelium with AHR. Here, we show that gob-5, a member of the calcium-activated chloride channel family, is a key molecule in the induction of murine asthma. Intratracheal administration of adenovirus-expressing antisense gob-5 RNA into AHR-model mice efficiently suppressed the asthma phenotype, including AHR and mucus overproduction. In contrast, overexpression of gob-5 in airway epithelia by using an adenoviral vector exacerbated the asthma phenotype. Introduction of either gob-5 or hCLCA1, the human counterpart of gob-5, into the human mucoepidermoid cell line NCI-H292 induced mucus production as well as MUC5AC expression. Our results indicated that gob-5 may play a critical role in murine asthma, and its human counterpart hCLCA1 is therefore a potential target for asthma therapy.

Animals↗
PubMed2001

Determination of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione, a novel metabolite of L-histidine, in tissue extracts from sunlight-irradiated rat by capillary electrophoresis.

Exposure of the skin to sunlight results in an increase in the content of epidermal urocanic acid, a key metabolite of L-histidine, and some portions of the metabolite penetrate into the body fluid. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (GS(CIE)), an adduct of glutathione and urocanic acid, was proposed to be an origin of a urinary compound, S-[2-carboxy-1-(1 H-imidazol-4-yl)ethyl]-L-cysteine (Cys(CIE)). Various catabolites of Cys(CIE) were also isolated from human urine previously. However, no direct evidence to show the existence of GS(CIE) as a biological material had been found. By using capillary electrophoresis, the glutathione adduct has now been found in the extracts of rat tissues from the kidney, liver, skin and blood when the rat was kept under conditions of sunlight irradiation after the fur on the dorsal skin had been clipped. On the other hand, no or a trace of GS(CIE) was determined in rat tissue extracts when the animal was kept indoor in usual manner. The glutathione adduct was isolated from the kidney extract of the sunlight-irradiated rat using ion-exchangers and high-voltage paper electrophoresis, and determined by fast-atom-bombardment mass spectrometry. These results indicate that GS(CIE) formation actually occurs in the body and that the formation is accelerated by exposing the rat to sunlight irradiation. From these findings, we propose an alternative pathway of histidine metabolism which is initiated by the adduction of urocanic acid to glutathione to form GS(CIE) and terminates with the formation of the urinary compounds via Cys(CIE).

Animals↗
PubMed2001

Simian virus 40 Vp1 DNA-binding domain is functionally separable from the overlapping nuclear localization signal and is required for effective virion formation and full viability.

A DNA-binding domain (DBD) was identified on simian virus 40 (SV40) major capsid protein Vp1, and the domain's function in the SV40 life cycle was examined. The DBD was mapped by assaying various recombinant Vp1 proteins for DNA binding in vitro. The carboxy-terminal 58-residue truncated Vp1DeltaC58 pentamer bound DNA with a K(d) of 1.8 x 10(-9) M in terms of the protein pentamer, while full-length Vp1 and carboxy-terminal-17-truncated Vp1DeltaC17 had comparable apparent K(d)s of 5.3 x 10(-9) to 7.3 x 10(-9) M in terms of the protein monomers. Previously identified on Vp1 was a nuclear localization signal (NLS) consisting of two N-terminal basic clusters, NLS1 (4-KRK-6) and NLS2 (15-KKPK-18). Vp1DeltaC58 pentamers harboring multiple-point mutations in NLS1 (NLSm1), NLS2 (NLSm2), or both basic clusters (NLSm1. 2) had progressively decreased DNA-binding activity, down to 0.7% of the Vp1DeltaC58 level for NLSm1. 2 Vp1. These data, along with those of N-terminally truncated proteins, placed the DBD in overlap with the bipartite NLS. The role of the Vp1 DBD during infection was investigated by taking advantage of NLS phenotypic complementation (N. Ishii, A. Nakanishi, M. Yamada, M. H. Macalalad, and H. Kasamatsu, J. Virol. 68:8209-8216, 1994), in which an NLS-defective Vp1 could localize to the nucleus in the presence of wild-type minor capsid proteins Vp2 and Vp3. This approach made it possible to dissect the role of the bifunctional Vp1 NLS-DBD in virion assembly in the nucleus. Mutants of the viable nonoverlapping SV40 (NO-SV40) DNA NLSm1, NLSm2, and NLSm1. 2 replicated normally following transfection into host cells and produced capsid proteins at normal levels. All mutant Vp1s were able to interact with Vp3 in vitro. The mutants NLSm1 and NLSm1. 2 were nonviable, and the mutant Vp1s unexpectedly failed to localize to the nucleus though Vp2 and Vp3 did, suggesting that the mutated NLS1 acted as a dominant signal for the cytoplasmic localization of Vp1. Mutant NLSm2, for which the mutant Vp1's nuclear localization defect was complemented by Vp2 and Vp3, displayed a 5,000-fold reduced viability. Analysis of NLSm2 DNA-transfected cell lysate revealed a 10-fold reduction in the level of DNase I-protected viral DNA, and yet virion-like particles were found among the DNase I-resistant material. Collective results support a role for Vp1 NLS2-DBD2 in the assembly of virion particles. The results also suggest that this determinant can function in the infection of new cells.

Animals↗
PubMed2001

The effect of a single dose of osteoprotegerin in postmenopausal women.

Osteoprotegerin (OPG), a tumor necrosis factor (TNF) receptor family member, is a critical regulator of bone resorption. It is an important inhibitor of the terminal differentiation and activation of osteoclasts. This randomized, double-blind, placebo-controlled, sequential dose escalation study was conducted in postmenopausal women to determine the effect of a single subcutaneous (s.c.) dose of OPG on bone resorption as indicated by the biochemical markers, urinary N-telopeptide (NTX) and deoxypyridinoline (DPD), which are stable collagen degradation products. NTX levels decreased within 12 h after OPG administration. At the highest dose administered (3.0 mg/kg), a mean percent decrease in NTX of approximately 80% was observed 4 days after dosing. Six weeks after dosing a mean decrease of 14% in NTX was observed. The levels of bone-specific alkaline phosphatase (BSAP), a marker of bone formation, did not change for approximately 3 weeks after dosing. Thereafter, a modest decrease, reaching approximately 30% at 6 weeks, was observed in the 3.0-mg/kg dose group. The rapid decrease from baseline in NTX and delayed decrease in BSAP indicated that OPG acted primarily on osteoclasts to decrease bone resorption. OPG injections are well tolerated. This study, for the first time, indicates that a single s.c. injection of OPG is effective in rapidly and profoundly reducing bone turnover for a sustained period and that OPG therefore may be effective in treatment of bone diseases characterized by increased bone resorption such as osteoporosis.

Double-Blind Method↗
PubMed2000

Subducted seamount imaged in the rupture zone of the 1946 nankaido earthquake

The Nankai Trough is a vigorous subduction zone where large earthquakes have been recorded since the seventh century, with a recurrence time of 100 to 200 years. The 1946 Nankaido earthquake was unusual, with a rupture zone estimated from long-period geodetic data that was more than twice as large as that derived from shorter period seismic data. In the center of this earthquake rupture zone, we used densely deployed ocean bottom seismographs to detect a subducted seamount 13 kilometers thick by 50 kilometers wide at a depth of 10 kilometers. We propose that this seamount might work as a barrier inhibiting brittle seismogenic rupture.

Journal Article↗
PubMed2000

Reduction of magnetic moments in very thin Cr layers of Fe/Cr multilayers: evidence from 119Sn Mössbauer spectroscopy.

Fe/Cr multilayers with monatomic Sn layers embedded in the Cr layers were grown epitaxially on MgO(001) substrates, and the magnetic hyperfine field at the 119Sn nuclear sites was examined using Mössbauer spectroscopy. It was found that nonzero hyperfine field is induced at the Sn sites at room temperature and that the value reduces drastically from 10 to 2 T when the Cr layer thickness decreases from 80 to 10 A. The result indicates that the Cr layers are magnetically ordered even when the thickness is very small and that the magnetic moments of Cr become smaller as the Cr layer thickness decreases.

Journal Article↗
PubMed2000

Usefulness of cerebral blood flow (CBF) measurements to predict the functional outcome for rehabilitation in patients with cerebrovascular disease (CVD).

PURPOSE: The objectives of this study were to (1) elucidate the relationship between the mean CBF in the whole brain (Av.mCBF) before rehabilitation of CVD patients and the BI score before and after rehabilitation, (2) determine whether the efficacy of rehabilitation can be predicted by measurement of the Av.mCBF, and (3) investigate what part of the brain was most important to improving the BI score. MATERIALS AND METHODS: The Av.mCBFs in 160 patients with CVD were calculated by Patlak plots with 99mTc-HMPAO before rehabilitation, and we determined the BI score before and after rehabilitation. Based on the BI scores before and after rehabilitation, patients were divided into four groups: Group A, BI = 100; Group B, 80 < or = BI < or = 99; Group C, 60 < or = BI < or = 79; Group D, 0 < or = BI < or = 59. We evaluated the relationship between the Av.mCBF and BI score before and after rehabilitation. RESULTS: The Av.mCBF before rehabilitation showed a tendency to be more correlated with the BI score after rehabilitation (r = 0.414, p < 0.0001) than before rehabilitation (r = 0.272, p = 0.0006). After rehabilitation, there was a tendency for the Av.mCBF value to increase in direct proportion to the BI score of the group: it was highest in Group A and lowest in Group D. The strongest correlation was found between the frontal lobe regional CBF before rehabilitation and the BI score after rehabilitation (r = 0.343, p < 0.0001). CONCLUSIONS: Measurement of the Av.mCBF before rehabilitation of CVD patients will permit prediction of the efficacy of rehabilitation. Also the regional CBF of the frontal lobe is most important for improving the BI score.

Adolescent↗
PubMed2000

Role of simian virus 40 Vp1 cysteines in virion infectivity.

We have developed a new nonoverlapping infectious viral genome (NO-SV40) in order to facilitate structure-based analysis of the simian virus 40 (SV40) life cycle. We first tested the role of cysteine residues in the formation of infectious virions by individually mutating the seven cysteines in the major capsid protein, Vp1. All seven cysteine mutants-C9A, C49A, C87A, C104A, C207S, C254A, and C267L-retained viability. In the crystal structure of SV40, disulfide bridges are formed between certain Cys104 residues on neighboring pentamers. However, our results show that none of these disulfide bonds are required for virion infectivity in culture. We also introduced five different mutations into Cys254, the most strictly conserved cysteine across the polyomavirus family. We found that C254L, C254S, C254G, C254Q, and C254R mutants all showed greatly reduced (around 100,000-fold) plaque-forming ability. These mutants had no apparent defect in viral DNA replication. Mutant Vp1's, as well as wild-type Vp2/3, were mostly localized in the nucleus. Further analysis of the C254L mutant revealed that the mutant Vp1 was able to form pentamers in vitro. DNase I-resistant virion-like particles were present in NO-SV40-C254L-transfected cell lysate, but at about 1/18 the amount in wild-type-transfected lysate. An examination of the three-dimensional structure reveals that Cys254 is buried near the surface of Vp1, so that it cannot form disulfide bonds, and is not involved in intrapentamer interactions, consistent with the normal pentamer formation by the C254L mutant. It is, however, located at a critical junction between three pentamers, on a conserved loop (G2H) that packs against the dual interpentamer Ca(2+)-binding sites and the invading C-terminal helix of an adjacent pentamer. The substitution by the larger side chains is predicted to cause a localized shift in the G2H loop, which may disrupt Ca(2+) ion coordination and the packing of the invading helix, consistent with the defect in virion assembly. Our experimental system thus allows dissection of structure-function relationships during the distinct steps of the SV40 life cycle.

Capsid↗
PubMed1999

The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III).

The ALS Functional Rating Scale (ALSFRS) is a validated rating instrument for monitoring the progression of disability in patients with amyotrophic lateral sclerosis (ALS). One weakness of the ALSFRS as originally designed was that it granted disproportionate weighting to limb and bulbar, as compared to respiratory, dysfunction. We have now validated a revised version of the ALSFRS, which incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support. The Revised ALSFRS (ALSFRS-R) retains the properties of the original scale and shows strong internal consistency and construct validity. ALSFRS-R scores correlate significantly with quality of life as measured by the Sickness Impact Profile, indicating that the quality of function is a strong determinant of quality of life in ALS.

Activities of Daily Living↗
PubMed1999

Toward a cancer therapy with boron-rich oligomeric phosphate diesters that target the cell nucleus.

The viability of boron neutron capture therapy depends on the development of tumor-targeting agents that contain large numbers of boron-10 (10B) atoms and are readily taken up by cells. Here we report on the selective uptake of homogeneous fluorescein-labeled nido-carboranyl oligomeric phosphate diesters (nido-OPDs) by the cell nucleus and their long-term retention after their delivery into the cytoplasm of TC7 cells by microinjection. All nido-OPDs accumulated in the cell nucleus within 2 h after microinjection. However, nido-OPDs in which the carborane cage was located on a side chain attached to the oligomeric backbone were redistributed between both the cytoplasm and nucleus after 24 h of incubation, whereas nido-OPDs in which the carborane cage was located along the oligomeric backbone remained primarily in the nucleus. Furthermore, cell-free incubation of digitonin-permeabilized TC7 cells with the nido-OPDs resulted in nuclear accumulation of the compounds, thus corroborating the microinjection studies. Our observation of fluorescence primarily located in the cell nucleus indicates that nuclear-specific uptake of sufficient amounts of 10B for effective boron neutron capture therapy ( approximately 10(8)-10(9) 10B atoms/tumor cell) via nido-OPDs is achievable.

Biological Transport↗
PubMed1999

[Linac-based stereotactic radiosurgery for arteriovenous malformations (AVMs) in brain: estimation for efficacy of therapeutic response using angiography].

The purpose of this study was to determine whether it is possible to predict the efficacy of therapeutic response to linac-based stereotactic radiosurgery for AVMs on the basis of the stagnation rate in the nidus, which was defined as follows: [(pooling time of contrast material in the nidus of AVM)/ (intracranial circulation time)] x 100. Cerebral angiograms of twenty-five AVMs were retrospectively evaluated, and the stagnation rates in the nidus were calculated before and one year after stereotactic radiosurgery. Reduction rate was also calculated by using angiography, and we statistically evaluated the relationship between the stagnation rates in the nidus and the reduction rates. The stagnation rates in the nidus prior to linac-based stereotactic radiosurgery were positively correlated with the reduction ratios of AVMs after stereotactic radiosurgery (r = 0.406, p = 0.0432). Our study suggested that a higher stagnation rate in the nidus of the AVM might be obliterated faster after linac-based stereotactic radiosurgery. Thus, calculation of the stagnation rate in the nidus before stereotactic radiosurgery is useful in predicting the efficacy of therapeutic response to linac-based stereotactic radiosurgery for AVMs.

Adolescent↗
PubMed1999

An autopsy report of graft-versus-host disease (GVHD) following blood transfusion.

A case of graft-versus-host disease (GVHD) associated with blood transfusion in a 71-year-old man is reported. The patient received transfusions (irradiation red cells M.A.P 14 units, fresh frozen plasma 11 units) and developed features of GVHD including fever, a skin rash, diarrhea, liver dysfunction, hypoplastic bone marrow, and pancytopenia. He died on day 32 posttransfusion. Pathologically, lymphocyte infiltration of skin and liver lesions, degeneration of small bile ducts, crypt cell necrosis in the gastrointestinal tract, and bone marrow hypoplasia were observed. Immunohistochemically, infiltrating lymphocytes were CD8+ T type, the result suggesting that they role a part in posttransfusion GVHD.

Aged↗
PubMed1998

Myocardial nuclear factor-kappaB activity and nitric oxide production in rejecting cardiac allografts.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a rapid response transcription factor for genes whose products are critical for inflammation and immunity. In a rat model of heterotopic cardiac transplantation, we studied NF-kappaB DNA binding activity and nitric oxide (.NO) production in untreated allografts and whether inhibition of NF-kappaB suppresses .NO production and prolongs graft survival. METHODS: In allograft recipients and isograft controls, NF-kappaB was assayed by electrophoretic mobility shift assay, daily from transplant until rejection. Myocardial .NO was directly detected in explanted allografts by electron spin resonance spectroscopy on day 6 after transplant. The potent inhibitor of NF-kappaB, pyrrolidine dithiocarbamate (PDTC; 250 mg/kg s.c.) was administered daily from transplant until day of rejection. The extent of graft lymphocytic infiltrate was assessed by routine hematoxylin and eosin staining. Immunohistochemical staining of NF-kappaB was per formed to identify the cell type responsible for NF-kappaB activity. RESULTS: A time-dependent increase in myocardial NF-kappaB activity was seen in untreated allografts as compared with isografts as determined by PhosphorImage analysis. Peak NF-kappaB activity occurred in allografts on day 4 with a ninefold increase as compared with isografts (24.0+/-3.7% vs. 2.7+/-0.5; P<0.05). On posttransplant day 6, electron spin resonance spectroscopy analysis of allografts demonstrated .NO identified by a triplet nitrogen signal centered at g=2.012 with hyperfine splitting of 17.5 Gauss, which is consistent with nitrosoheme formation and low-field signals at g=2.08 and g=2.03 consistent with nitrosomyoglobin. These signals were not seen in native hearts of allograft recipients. With PDTC administration, a threefold decrease in NF-kappaB activity within the transplanted heart was observed on posttransplant day 5 as compared with untreated allografts (9.7+/-1.6% vs. 23.5+/-2.5%; P<0.01). PDTC prolonged graft survival as compared with untreated allografts (11.7+/-0.3 vs. 6.6+/-0.2 days; P<0.05) and reduced the intensity of the nitrosoheme and nitrosomyoglobin signals. Allograft mononuclear cell infiltrate correlated with peak NF-kappaB activity with peak infiltrate on posttransplant day 4. PDTC treatment had no effect on the extent of infiltrate. Immunohistochemical staining localized NF-kappaB to the infiltrating mononuclear cells on posttransplant day 5. CONCLUSION: These data support a role for NF-kappaB in allograft rejection.

Animals↗