頭頸部扁平上皮癌の 5 年生存率が最近数十年間で大きな改善が認められない理由の一つとして、この癌がしばしば放射線耐性を獲得することが挙げられる。放射線耐性の頭頸部扁平上皮癌細胞に対する -301 感染と放射線治療の併用療法の抗腫瘍効果について報告する。まず in vitro および in vivo で -301 感染と放射線治療を併用し、その相乗効果の有無について検討した。次にアポトーシス誘導および DNA 修復能を検討した。その結果、放射線耐性細胞株に対する -301 感染と放射線治療の併用は in vitro および in vivo で単独治療と比較して有意に高い抗腫瘍効果を発揮し、相乗効果が認められた。 -301 感染は用量依存性に DNA 修復能に関連する複合体の発現増加を抑制した。 -301 感染と放射線照射の併用は、これらの機序を通して頭頸部扁平上皮癌細胞の放射線耐性を減弱させる新たな治療戦略となり得る可能性が示唆された。

抄録全体を表示

The odorant-binding protein () functions in chemosensation in insects. Two genes, and , are involved in the evolution of the unique host-plant preference in Drosophila sechellia. Comparative analysis of the

Obp

57d/e genomic sequences in the Drosophila melanogaster species group has revealed that the rapid evolution of and has resulted in functional divergence between the two genes. Here, using D. melanogaster knockout strains generated by gene targeting, we examined the roles of and in behavioral response to a series of fatty acids. In the taste-based oviposition-site preference assay, the knockout flies showed stronger preference for acids than wild-type flies, indicating that the normal functions of and are associated with the suppression of positive preference for C₆-C₉ acids. Heterozygotes for each knockout haplotype also exhibited a significantly different behavioral response compared with wild-type flies, suggesting that and have a gene dosage effect on behavior. In contrast, the wild-type and knockout flies exhibited similar responses in the feeding assay and the odor-based free-walking assay, suggesting that the two OBPs’ contribution to feeding and olfactory behaviors is small. Taken together, our results demonstrated that each of and in D. melanogaster contributes to the determination of reproductive sites, suggesting that the two genes play an important role in ecological adaptation of Drosophila.

抄録全体を表示

In bullfrogs with glottis occluded and lungs artificially ventilated, the buccal cavity contractors (BCconts) were found to contract isometrically, meaning that peak buccal pressure () well represents the total inspiratory nerve activities (TIAs) of BCconts. Unilateral sectioning of the trigeminal (V), hypoglossal, facial, or vagal nerve reduced the magnitude of by 43.3, 28.8, 10.9, or 4.3%, respectively. The integrated peak V activity (I-ENGv) showed a linear relationship to (r=0.944) in the glottis occluded frog, but a curvilinear relationship to peak buccal pressure (peak BP) in the spontaneously breathing frog during inflation period. The latter relationship was better fitted by a hyperbolic equation (r=0.943) than by a linear equation (r=0.927) (p<0.001). The relationship between I-ENGv and peak BP showed a hysteresis during deflation period. It was suggested that both I-ENGv and peak BP can be used as a measure of TIAs, but use of the latter requires some reservations.

抄録全体を表示

The objective of this study was to investigate the effects of superfine grinding on the physicochemical and antioxidant properties of oat bran polysaccharides (). The solubility of increased from 8.1 to 11.3 mg/mL. The average molecular weights of raw (rOBP) and superfine ground (sOBP) were 655.6 and 489.6 kDa, respectively. The intrinsic viscosity of sOBP (4.58 mL/mg) was extremely lower than that of rOBP (94.75 mL/mg). The endothermic enthaphy change (ΔH) values of with different water contents (0%, 50%, and 75%) changed from −328.79 J/g, −942.41 J/g, and −1.94 kJ/g to −197.01 J/g, −703.29 J/g, and −1.50 kJ/g, respectively. After being superfine grinding treated, sOBP exhibited higher antioxidant activities than rOBP based on FRAP, DPPH radical scavenging, and ABTS radical scavenging activities. The results suggested that superfine grinding treatment enhanced antioxidant activities. Physicochemical properties, including molecular weight, monosaccharide composition and solubility were key factors in antioxidant activities.

抄録全体を表示

Non-contiguous orthogonal frequency-division multiplexing (OFDM) is a promising technique for cognitive radio systems. The secondary users transmit on the selected subcarriers to avoid the frequencies being used by the primary users. However, the out-of-band power (

) of the OFDM-modulated tones induces interference to the primary users. Another major drawback of OFDM-based system is their high peak-to-average power ratio (PAPR). In this paper, algorithms are proposed to jointly reduce the and the PAPR for non-contiguous OFDM based on the method of alternating projections onto convex sets. Several OFDM subcarriers are selected to accommodate the adjusting weights for and PAPR reduction. The frequency-domain OFDM symbol is projected onto two convex sets that are defined according to the requirements and the PAPR limits. Each projection iteration solves a convex optimization problem. The projection onto the set constrained by the requirement can be calculated using an iterative algorithm which has low computational complexity. Simulation results show good performance of joint reduction of the and the PAPR. The proposed algorithms converge quickly in a few iterations.

抄録全体を表示

Insect odorant-binding proteins function in the sensing of odors, tastes, and pheromones. Genes encoding two odorant-binding proteins, and , were identified to be involved in the behavioral adaptation of Drosophila sechellia to its host plant. The two genes are expressed in cells associated with taste sensilla on the legs, and the expression pattern in the legs is conserved among closely related species. To identify the cis-regulatory elements necessary for the expression in the leg sensilla, the promoter sequences of and were compared among species. Two types of conserved sequence-motifs were found as candidate cis-regulatory elements. Functions of these conserved elements in the promoters of D. melanogaster and were examined by using a newly constructed vector that combines the advantages of φC31 integrase-based transformation and gypsy transposable-element-derived insulators. By GFP-reporter assay using the new vector, it was confirmed that these conserved elements are necessary for the expression in the legs, working synergistically with each other to affect the expression level. Single-nucleotide substitutions in these elements dramatically changed the promoter activity. These results provide insight into the molecular mechanism for evolution of adaptive behavior via modulation of expression levels.

抄録全体を表示

Introduction: Occupation-based practice (

) is seldom performed for people with severe acute cerebrovascular accidents (CVA). This study aimed to explore the conditions and situations in which occupational therapists (OTs) provide to patients with severe acute CVA.

Methods: Semi-structured interviews with eight OTs were conducted to determine

for patients with severe acute CVA. The participants were OTs who had conducted for patients with CVA in an acute care setting. Data were analyzed using inductive analysis. The procedures were: (i) to create verbatim records, (ii) to separate the verbatim records by context and to code while comparing the differences and commonalities of each code, (iii) to create subcategories, and (iv) to create categories by grouping together the subcategories with concepts that have similarities.

Results: The participants (OTs) reported that they have performed

for patients with severe acute CVA patients when (1) environments are available to perform occupations, (2) OTs establish good quality teamwork with multi-disciplinary professionals, (3) OTs emphasize patient-centered practice, (4) patients express their wishes to do occupations, (5) patients and families are getting to ready to resume occupation, (6) patients' occupations are actionable and meaningful.

Conclusion: The OTs' belief, the supportive environment, the client and family oriented toward occupations, and the identification of actionable and meaningful occupations were critical for the OTs to implement

for the severe acute CVA patients. These results could provide OTs with insights for promoting in acute settings, especially working with patients with severe acute CVA.

抄録全体を表示

　骨・軟部肉腫は, 一部に治療抵抗性で予後の悪い症例が存在するため, 新たな治療法の確立が重要な課題である.　我々は, 5型アデノウイルスを基本骨格として, テロメラーゼ活性に依存して増殖する腫瘍融解ウイルス（-301）や, coxsackie and adenovirus receptor（CAR）陰性の腫瘍細胞に感染するファイバー改変型ウイルス（-405）を用い, 骨・軟部肉腫細胞に対する抗腫瘍効果を検討した.　14種類の骨・軟部肉腫細胞株に対して-301の細胞障害活性を検討し, 12種類の細胞株で-301に感受性を認めた.　また, -301の細胞障害活性はCARの発現と相関していた.　さらに, テロメラーゼ活性の低い細胞に対しても, 5型アデノウイルスの複製に必須のE1Aによりテロメラーゼ活性の増強効果がおこり, 強い抗腫瘍活性を示すことを明らかにした.　次に, 骨肉腫脛骨同所性移植動物モデルを作成し-301を投与したところ, -301投与群では対象群と比べて有意に腫瘍増殖を抑制した.　最後に, -301に感受性を認めなかったCAR陰性細胞株に対して-405を用いて検討し, -405が有効に作用することを確認した.　-301や-405を用いたウイルス療法は, 骨・軟部肉腫に対する新たな治療法となる可能性がある.

抄録全体を表示

Background: Masked hypertension (MH) is characterized by its hidden nature and poor prognosis. However, it is not practical to routinely recommend home or ambulatory blood pressure monitoring (HBP or AMBP) to all patients with apparently well-controlled BP. The purpose of this study is to present, within the group of patients with well-controlled office BP (), the clinical predictors of MH and to evaluate the gap (ie, the `mask effect' (ME)) between and HBP. Methods and Results: BP was measured at the outpatient clinic and at home in 1,019 treated hypertensive patients. Candidate predictors for MH were analyzed within 511 patients with well-controlled (45.6% men, 57.1±9.0 years). Among them, the prevalence of MH was 20.9% (n=107). In the multivariate-adjusted analysis, the risk of MH increased with high serum fasting blood glucose level (odds ratio (OR) 1.009, 95% confidence interval (CI): 1.001-1.018, P=0.020), higher systolic (OR 1.075, 95%CI 1.045-1.106, P<0.001), higher diastolic (OR 1.045, 95%CI 1.007-1.084, P=0.019) and the number of antihypertensive medications (OR 1.320, 95%CI 1.113-1.804, P=0.021). Furthermore, systolic HBP correlated well with systolic (r=0.351, P<0.001) and with the degree of systolic ME (r=-0.672, P<0.001). Conclusions: To recognize MH, it is practical to investigate those patients who are taking multiple antihypertensive drugs and have a high with a high FBG level. The term "ME" identifies MH more appropriately than the term "negative white-coat effect". (Circ J 2011; 75: 357-365)

抄録全体を表示

Point
1）頸動脈エコーは非侵襲検査で，血管壁の構造と血流状態が同時にリアルタイムに観察できる．
2）頸動脈エコーは早期の動脈硬化性病変の評価にも有効である．
3）頸動脈壁のエコー像は，前壁側，後壁側ともに高エコー層・低エコー層・高エコー層の三層構造として観察される．
4）健常者でのmax-IMTは加齢に伴い増厚し，その値は10年で0.08～0.10mmといわれている．
5）頸動脈エコーでは，プラークの破綻（plaque rupture）により，脳塞栓症を合併する不安定型プラークの検出が重要である．

抄録全体を表示

[Purpose] Aquaporin5 (AQP5) is a water-selective channel protein and located at apical membranes of the acinar cells of the lacrimal glands. The tear secretion is regulated exactly by on/off mechanism, suggesting that AQP5 is regulated by gating. However, the gating mechanisms are still unknown. Our purpose is to clarify the gating mechanisms of AQP5 in the lacrimal gland acinar cells. [Methods] Poly(A) RNAs from the lacrimal glands were prepared from 5-6 week-old BALB/c mouse. The poly(A) RNAs and AQP5 cRNA were microinjected into Xenopus laevis oocytes to examine if AQP5 inhibitory factor exists in the lacrimal glands. The inhibitory factors were purified from the mouse lacrimal glands by affinity chromatography. [Results] The osmotic water permeability of AQP5 was inhibited by the co-injection of poly(A)RNAs from the lacrimal glands into oocytes. In addition, dibutyryl-cAMP and C-terminal peptide of AQP5 restored the suppressed water permeability of AQP5 oocytes. Using affinity chromatography, odorant-binding protein-1a (-1a) is isolated from mouse lacrimal glands as one of the inhibitory factors for AQP5. -Ia is abundantly expressed in lacrimal glands. Antisense DNA to -1a also restored the suppressed water permeability of AQP5 oocytes. [Conclusion] AQP5 is gated by binding of -1a to the C-terminus of the molecule, which may be regulated by phosphorylation. Tear secretion might be regulated by the gating of AQP5. [Jpn J Physiol 55 Suppl:S35 (2005)]

抄録全体を表示

The advent of electronic noses opened a new kind of analytical approach, which offers an easy, quick, and cheap measurement comparing to conventional analytical approaches. It has potential applications on many different fields, such as assessment of various foodstuffs and beverages, environmental contamination monitoring and medical diagnostics etc. In this study, we used odorant binding protein () as odor-sensing material for developing such kind of artificial odorant biosensor. And biological films of -1F (rat ) were deposited by Langmuir-Blodgett (LB) technique on gold electrode previously functionalised with 1-octadecanethiol (ODT) by self-assembled monolayers (SAMs). It is known that successful immobilization of the Langmuir-Blodgett films depends strongly on the characteristics, particularly stability, of the corresponding Langmuir films at the air/water interface. Hence the characteristics of monolayer of amphiphile octadecylamine (ODA) and the mixed monolayer of ODA/ were studied. Electrochemical impedance spectroscopy (EIS) was used to monitor the response of the system to a specific odorant molecule, isoamyl acetate.

抄録全体を表示

In recent times, oncolytic viruses expressing an extraneous gene have attracted great interest; in fact, they have been engaged in multiple applications, such as medicine for cancer. Our group made an oncolytic adenovirus, namely,

-301, for use in treating solid cancers and press clinical trial to get approval for a pharmaceutical product. In this study, we applied a flow cytometry-based method to determine the titer of adenoviruses expressing an extraneous gene as well as assess their quality. We considered using the green fluorescent protein (GFP)₅₀ titer as a measure of viral quality. The GFP₅₀ titer (GFP₅₀/mL) is the viral load required to render the HeLa S3 cell line 50% GFP-positive by analysing flow cytometry data. We measured the GFP₅₀ titers for three types of recombinant adenoviruses (-401, -1101, and -1106). We compared GFP₅₀/mL and tissue culture infectious dose (TCID₅₀/mL), a conventional titration index, and found that these titers showed a linear correlation, with a correlation coefficient of >0.9. Moreover, GFP₅₀/mL showed high repetitive accuracy. We expect this flow cytometry-based method to be useful in case of clinically relevant viruses expressing an extraneous gene, in particular, to control viral quality.

抄録全体を表示

作業に根ざした実践（Occupation-Based Practice 2.0： 2.0）は，クライエントの作業機能障害を評価しつつ，それを取り巻く信念対立に対処していく方法論である．本報告では，地域在住で脳卒中後遺症を有するクライエントに対して 2.0を用いた評価と介入を実施し，訪問作業療法（訪問OT）における 2.0の臨床有用性を検討した．その結果，作業機能障害の改善と生活機能の向上が見られ，作業療法士，家族とクライエントの間で生じた信念対立の解明が進んだ． 2.0は，作業機能障害の改善に向けて訪問OTの方針の共有と，状況に応じ様々な方法の使用ができると考えられた．また，クライエントや周囲の人々と協業した訪問OTを促進できた．

抄録全体を表示

Since 1987 we have been working with the establishment of the sea floor observation stations in order to detect long-term geophysical changes. Study of the changes of geomagnetic field is one of the most important works to be carried out on the station. The sea floor observation station is a fixed and nonmagnetic platform installed firmly on the sea floor, which is easily accessible by manned submersibles. We have installed three such observation stations in the Sagami Bay which is close to Tokyo. The operation and observation were carried out with the aid of the Japanese Submersible SHINKAI 2000 every year. Measurements were made four times in the last four years. Duration of the measurement was from 1 hour to 25 hours depending on the conditions of the submersible. The equipment used to measure the geomagnetic total force is a proton magnetometer specially designed for the sea floor. The sensor is a toroidal coil dipped totally in Kerosene oil which is pressure-balanced by means of Beryllium-Copper bellows. The magnetometer is installed on the platform exactly in the same fashion every time. Transportation and installation are made by the submersible using manipulators. By comparing the data from the sea floor with those of the land geomagnetic stations, we confirmed the feasibility of detecting changes of geomagnetic total force on the sea floor.

抄録全体を表示

DNA修復機能阻害は放射線感受性を増強させるため，DNA修復に関与する因子の阻害剤は放射線増感剤となり得る．我々の開発したテロメラーゼ依存的腫瘍融解アデノウイルス製剤-301（テロメライシン）は，アデノウイルスE1B55kDaタンパクを介して細胞のDNA修復に重要な役割を果たすMRN複合体（Mre11，Rad50，NBS1）を分解する機能を有する．このMRN複合体の分解によりATM（ataxia-telangiectasia mutated）の活性化が抑制され結果的にDNA修復機構が阻害される．我々は-301と放射線との併用が強力な相乗効果を生み出すことをマウスの皮下腫瘍モデルおよび食道癌同所性モデルにおいて証明した．これらの結果は-301が将来有望な放射線増感剤となり得ることだけでなく，E1B55kDaタンパクを産生する腫瘍融解アデノウイルス製剤と放射線との併用が悪性腫瘍に対する有力な治療戦略となり得ることを示す．

抄録全体を表示