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Objective Optimal dose-fractionation regimen of stereotactic body radiotherapy for peripheral early-stage non-small cell lung cancer remains unclear. We retrospectively investigated outcomes of stereotactic body radiotherapy using CyberKnife at 54 Gy in three fractions in 26 patients (median age: 76 years) with pathologically confirmed T1b–T2aN0M0 non-small cell lung cancer. Methods A 54 Gy in three fractions was prescribed to cover the 99% of gross tumor volume. We estimated cumulative local control, progression-free survival and overall survival rates (Kaplan–Meier method), and toxicity (Common Toxicity Criteria for Adverse Events, version 5.0). Results All the tumors were located at peripheral area of lung. Mean distance from chest wall to tumor was 6.5 mm (range: 0–32 mm). The patients’ pathological diagnoses were: adenocarcinoma: n = 18, squamous cell carcinoma: n = 7 and non-small cell carcinoma: n = 1. Their stages were T1b: n = 9, T1c: n = 14 and T2a: n = 3. Median follow-up was 24 months (range: 6–54). Cumulative 2-year effect rates were local control: 100%, progression-free survival 70% and overall survival: 92%. Twenty patients developed grade one radiation pneumonitis, but grade 2 or greater radiation pneumonitis was not observed. Conclusions We found CyberKnife-stereotactic body radiotherapy for pathologically confirmed T1b–T2aN0M0 non-small cell lung cancer to be effective and safe. However, these results should be validated with a larger patient cohort and prospective follow-up monitoring.

The feasibility of intensity modulated radiotherapy (IMRT) with involved field radiotherapy (IFRT) for Japanese patients with locally advanced non-small cell lung cancer (LA-NSCLC) remains unclear. Here we reviewed our initial experience of IMRT with IFRT for Japanese patients with LA-NSCLC to evaluate the feasibility of the treatment. Twenty LA-NSCLC patients who were treated with IMRT with IFRT during November 2019 to October 2020 were retrospectively analyzed. All patients received 60 Gy in 30 fractions of IMRT and were administered concurrent platinum-based chemotherapy. The median patient age was 71 years old and the group included 15 men and 5 women. The patient group included 2 patients with stage IIB, 11 patients with stage IIIA, 5 patients with stage IIIB, and 2 patients with stage IIIC disease. Histological diagnosis was squamous cell carcinoma in 14 patients, adenocarcinoma in 5 patients, and non-small cell lung cancer in 1 patient. The median follow-up period was 8 months. The incidence of grade 3 or greater pneumonitis was 5%, and grade 3 or greater esophagitis was not observed. None of the patients developed regional lymph node, with only recurrence reported so far. These findings indicate that IMRT with IFRT for Japanese patients with LA-NSCLC is feasible in terms of acute toxicity. Further study with a larger number of patients and longer follow-up to clarify the effect of treatment on patient prognosis is required.

Background Palliative radiotherapy is one of the effective treatments for pelvic tumor with bleeding or pain. In this study, we evaluated the safety and efficacy of palliative radiotherapy (RT) for symptomatic pelvic tumors when delivered as 25 Gy in 5 fractions. Methods We retrospectively analyzed 34 patients (gynecological cancer: n = 14, rectal cancer: n = 5, metastatic pelvic bone tumor: n = 7, metastatic pelvic lymph node tumor: n = 5, synovial sarcoma of the pelvis: n = 1, prostate cancer: n = 1, and urothelial cancer: n = 1, who were treated between July 2016 and July 2021. Their symptoms were bleeding in 16 patients, pain in 17 patients, and both bleeding and pain in 1 patient. Hemostatic effect of RT was evaluated with pre and post treatment hemoglobin (Hb) values. If the Hb level reached a nadir and increased thereafter, we considered that there is a hemostatic response. Pain was evaluated with a numerical rating scale (NRS) and treatment response was defined as a decrease in NRS. Results Their median follow-up period was 4 months. Hemostatic response was observed in 82% of patients (14 of 17 patients). Pain relief response was observed in 78% of patients (14 of 18 patients). Acute adverse effects (AEs) included grade 1 diarrhea: n = 3, grade 1 dermatitis: n = 1, and grade 1 urinary frequency: n = 1; late AEs were not observed so far. Conclusions We think that 25 Gy of palliative RT in 5 fractions seems to be safe and effective for symptomatic pelvic tumors, similar to conventional palliative RT schedules.

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.

Background Durvalumab after concurrent chemoradiotherapy (CCRT) for locally advanced non‐small cell lung cancer (LA‐NSCLC) has been found to significantly improve overall survival (OS). However, the effect of durvalumab on local control remains unclear. Here, we evaluated the effect of the durvalumab on local control in comparison with the clinical result of patients treated with CCRT alone. Methods A total of 120 LA‐NSCLC patients including 76 patients with CCRT alone and 44 patients with CCRT followed by durvalumab were analyzed. Baseline patient characteristics of CCRT alone cohort and durvalumab cohort were compared with student's t test or Mann–Whitney U test for continuous variables and with chi‐squared test for categorical variables. Local control (LC), progression free survival (PFS) and OS rates were estimated using the Kaplan–Meier method and compared with the log‐rank test. Results There were 19 patients with stage II disease and 101 patients with stage III disease. Age, sex, histopathological type, T classification, N classification, clinical stage, tumor volume and dose fractionation schedule were not significantly different between the CCRT alone and durvalumab cohorts. The one‐year LC rate was significantly higher in the durvalumab cohort (86%) compared with the CCRT alone cohort (62%) (P = 0.005), whereas no significant difference was observed in either PFS (P = 0.864) or OS (P = 0.443) between the CCRT and durvalumab cohorts. Conclusions The one‐year LC rate was significantly higher in the durvalumab cohort compared with the CCRT alone cohort. Although the follow‐up period was too short to draw definitive conclusions, the study revealed that durvalumab might have a significant effect on LC. Key points Significant findings of the study Effect of durvalumab on local control after chemoradiotherapy for locally advanced non‐small cell lung cancer is unclear What this study adds The one‐year local control rate of chemoradiotherapy followed by durvalumab was significantly higher compared with chemoradiotherapy alone., The one‐year local control rate was 83% in the durvalumab cohort and 62% in the CCRT alone cohort, which was significantly different.

To evaluate treatment results and investigate predictors of local control.In this retrospective study of 236 patients with cervical cancer, we administered CT-based adaptive brachytherapy (BT) in combination with whole- pelvic (WP)- and central shielding (CS)- external beam radiotherapy (EBRT) with or without chemotherapy. The study cohort comprised patients with cervical cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy between June 2013 and March 2019. Local control (LC), overall survival (OS), and late toxicity were evaluated. Predictive factors for LC were analyzed by univariate and multivariate analyses.Median doses of WP- and CS-EBRT and BT were 30.6 GyThe combination of WP- and CS-EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC outcomes with low rates of late toxicities for patients with small or medium-sized tumors. However, LC was less favorable for patients who had large T3 disease, and the use of CS requires caution in these patients.

The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P

Three Fortunella (kumquat) species, the Meiwa kumquat (F. crassifolia Swingle), the Round kumquat [F. japonica (Thunb.) Swingle] and the Changshou kumquat (F. obovata hort. ex Tanaka), showing tetraploid, which had been induced by treating the seeds with colchicine, were examined for origin and horticultural characteristics (e. g. morphology of leaves, flowers, pollen and fruits). Additionally, these tetraploid kumquats were crossed to produce triploid kumquats. All of the tetraploids were confirmed to be derived from the nucellar embryo of each original kumquat by examining their chromosomal composition with chromomycin A3 staining. All of the tetraploid kumquats had the typical morphological characteristics of tetraploid Citrus plants, such as round and thick leaves, and large flowers and pollen grains. On the other hand, the fruits of these tetraploid plants showed desirable traits for kumquats such as thicker pericarp and higher soluble solids content. Furthermore, when these tetraploids were crossed with some diploid cultivars, triploid progenies were obtained from almost all of the cross combinations.

A ploidy chimera of the Meiwa kumquat (Fortunella crassifolia Swingle), which had been induced by treating the nucellar embryos with colchicine, and had diploid (2n = 2x = 18) and tetraploid (2n = 4x = 36) cells, was examined for its ploidy level, morphological characteristics, and sizes of its cells in its leaves, flowers, and fruits to reveal the ploidy level of each histogenic layer. Furthermore, the chimera was crossed with the diploid kumquat to evaluate the ploidy level of its reproductive organs. The morphological characteristics and the sizes of the cells in the leaves, flowers, and fruits of the chimera were similar to those of the tetraploid Meiwa kumquat and the ploidy periclinal chimera known as “Yubeni,” with diploids in the histogenic layer I (L1) and tetraploids in the histogenic layer II (L2) and III (L3). However, the epidermis derived from the L1 of the chimera showed the same result as the diploid Meiwa kumquat in all organs and cells. The sexual organs derived from the L2 of the chimera were significantly larger than those of the diploid. Moreover, the ploidy level of the seedlings obtained from the chimera was mostly tetraploid. In the midrib derived from the L3, the chimera displayed the fluorescence intensity of a tetraploid by flow cytometric analysis and had the same size of the cells as the tetraploid and the Yubeni. According to these results, the chimera is thought to be a ploidy periclinal chimera with diploid cells in the outermost layer (L1) and tetraploid cells in the inner layers (L2 and L3) of the shoot apical meristem. The chimera had desirable fruit traits for a kumquat such as a thick pericarp, a high sugar content, and a small number of developed seeds. Furthermore, triploid progenies were obtained from reciprocal crosses between the chimera and diploid kumquat.

ニンポウキンカン種子へのコルヒチン処理から得た四倍体6系統（No.5，No.6，No.8，No.12，No.18およびNo.19）の倍数性と発生起源の確認，樹体および果実の特性調査を行うとともに，二倍体との交雑による三倍体の作出を試みた．これら6系統は，CMA染色による核型分析により，すべて珠心胚由来であることが推察された．倍数性解析を行ったところ，No.8は二倍体と四倍体の倍数性キメラであり，その他5系統は四倍体であった．四倍体5系統は，二倍体と比較して葉，花および花粉が大きく，花粉稔性が低くなるなどの四倍体特有の形質を示した．一方，果実は二倍体と比較して四倍体の方が厚皮，高糖度および少核となり，キンカンにとって望ましい形質を有していた．No.8は表皮系が二倍体同様の特徴を示したものの，その他の特性は四倍体と類似した．二倍体との正逆交雑におけるほとんどの交雑組合せで三倍体が得られた．

We have developed a novel synthetic method that enables us to easily synthesize metal-capsulated carbon nanotubes (CNTs) in a laboratory by using a combined technology of electrospinning-metallization and microwave heating. These techniques greatly shorten the time for the synthesis of the CNTs in comparison with the conventional methods. TEM analysis confirmed a successful formation of the CNTs, and the resulting CNTs were multi-walled and found to be about 25–100 nm in diameters. The products prepared by heating at 600 and 900°C exhibited less-developed and strongly curved CNTs, whereas the products prepared by heating at 700 and 800°C relatively well-developed long CNTs. Copyright © 2010 John Wiley & Sons, Ltd.

The conductive metallic nanofibers were prepared by using a combined technology of electrospinning and metallization. The electrospun polyurethane and poly(vinyl alcohol) (PVA) nanofibers are metallized with different thicknesses of metal (Cu, Ni) layer via a metallization. The thickness of the metallic layer, which is ranging from 50 nm to 200 nm, was controlled. The resultant metallized nanofibers are characterized using field emission scanning electron microscopy (FE-SEM), wide angle X-ray diffraction (WAXD), and thermogravimetric analysis (TGA). FE-SEM micrographs demonstrate that the nano-scaled metallic layers are well deposited onto the nanofibers. TGA result indicates that thermal stability of the metallized nanofibers was enhanced due to the barrier effects of the metallic thin layer. WAXD data also confirm that the metallic layers are well deposited onto the nanofibers. Remarkably, the fibrous morphologies were satisfactorily conserved after removal of the nanofiber template by heat treatment at ca. 400 oC for 24 hr., suggesting the successful deposition of metal layer onto the nanofiber template, and thereby resulted in the formation of metallic nanofibers and nanotubes depending on the diameter of electrospun nanofibers and the thickness of the deposited metallic layers in the conductive metallic nanofibers. In addition, it was observed that the metallized nanofibers exhibit higher conductive properties depending on the thickness of the deposited metallic layers.

The metallized hybrid nanofiber webs were prepared by using a combined technology of electrostatic spinning and metallization. The electrospun polyurethane (PU) nanofibers were metallized with different thicknesses of copper layer via metal vapor deposition technique. The thickness of the copper layer, which ranges from 10 to 100 nm, was monitored and controlled. The resultant metallized hybrid nanofiber webs were characterized using field emission scanning electron microscopy (FE-SEM), wide angle X-ray diffraction (WAXD), and thermogravimetric analysis (TGA). FE-SEM images demonstrated that the nanoscaled copper layers are well deposited on the surface of the PU nanofibers. TGA result indicated that the thermal stability of the metallized hybrid PU nanofibers was dramatically enhanced due to the barrier effects of thin metallic copper layer. WAXD data confirmed that the crystalline copper layers were well deposited onto the PU nanofibers. Moreover, the mechanical properties of the metallized hybrid PU nanofiber webs were increased with increase in the thickness of deposited copper layer. Unlike the organic PU nanofiber webs, it was observed that the metallized hybrid PU nanofiber webs showed higher conductive properties depending on the thickness of the deposited copper layer. Copyright © 2009 John Wiley & Sons, Ltd.

This study focuses on the interspecific variation in the distribution and structure of pits between vessels and imperforate tracheary elements. Specimens from the outer sapwood of eight species, in which vessel elements are frequently in contact with fibres and/or tracheids, were prepared using two different techniques and examined by field-emission scanning electron microscopy. In three species in which vessels are surrounded by vasicentric tracheids and/or fibres with distinctly bordered pits, pit pairs frequently occurred in walls between vessels and imperforate tracheary elements. In the five species in which vessels are in contact with fibres with indistinctly bordered pits, no or very few pit pairs were present, and blind pits were often found. Blind pits were exclusively present in vessel elements in some species, while they were restricted to imperforate tracheary elements in other species. The nature of vessel to imperforate tracheary element pitting appears to depend on tracheary element specialization.

アレンドロン酸ナトリウム水和物（以下，アレンドロネート）は，窒素含有ビスホスホネート系化合物であり，強力な骨吸収抑制作用を持つ骨粗鬆症治療薬である．アレンドロネートは，海外において1993年にイタリアで承認されたのをはじめ，2006年1月までに95ヵ国以上で許認可を受けている．本邦においても骨粗鬆症に対するアレンドロネート5 mg1日1回投与製剤の有効性および安全性が確認され，2001年8月よりフォサマック錠5（万有製薬），ボナロン錠5 mg（帝人，現帝人ファーマ）の販売名で販売されている．また，アレンドロネートの週1回投与製剤は，海外においてその有効性・安全性が証明され80ヵ国以上で承認されている．本邦においても，腰椎骨密度を評価項目として第III相二重盲検比較試験を実施し，アレンドロネート35 mg週1回投与製剤は，アレンドロネート5 mg1日1回投与製剤と同等の有効性および同様の安全性を有することが示され，2006年7月に承認された．体内に吸収されたアレンドロネートは，骨吸収部位に特異的に分布し，数週間にわたり持続的に薬理作用を発揮し，その後効果の減弱とともに代謝されず徐々に排泄されるというユニークな体内動態を示す．このような特性から，1日1回投与量の7倍量に相当するアレンドロネートを週1回投与しても同等の骨量増加効果が得られると考えられた．また，内服のビスホスホネート系薬剤に共通する食道粘膜刺激に基づく障害は，投与間隔を空けることにより軽減する可能性が示唆される成績も報告され，週1回の投与法は安全性において有利であるとも考えられた．アレンドロネート等のビスホスホネート系薬剤は，食事による吸収阻害，ならびに食道への逆流による粘膜刺激を避けるため，朝起床時，空腹時に約180 mLの水とともに服用し，その後少なくとも30分は飲食および他の薬剤の服用を避け，また上体を起こした状態を維持しなければならない．そのため，このような服用方法に不便さを感じ，更に治療継続が困難になる患者も少なくない．骨粗鬆症のような慢性疾患の薬物療法において，服薬の利便性は，服薬コンプライアンスを高める上で重要である．したがって，アレンドロネート週1回の用法の登場は，患者にとって服薬の利便性に繋がると同時に患者のライフスタイルに合わせた服薬方法の選択肢が増えることになり，服薬コンプライアンスの向上に寄与するものと期待される．

This study focused on the effects of tacalcitol (1,24 (R) (OH)2D3, TV-02) ointment (20 micro g/g) on cutaneous inflammation, epidermal proliferation, and differentiation and compared them with tacalcitol ointment (2 micro g/g) and other anti-psoriatic ointments using hairless mice. Tacalcitol ointment (0, 2 and 20 micro g/g) significantly inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cutaneous inflammation, histopathologically. The effect of tacalcitol ointment (20 micro g/g) on cutaneous inflammation was much stronger than that of tacalcitol ointment (0, 2 micro g/g), and as effective as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). Tacalcitol ointment (20 micro g/g) also significantly inhibited TPA-induced myeloperoxidase (MPO) activity, as effectively as calcipotriol ointment (50 micro g/g) or betamethasone valerate ointment (1.2 mg/g). The effect of tacalcitol ointment on epidermal proliferation [ornithine decarboxylase (ODC) activity] and differentiation [transglutaminase (TGase) activity] was dose-dependent from 0 micro g/g to 20 micro g/g. The effect of tacalcitol ointments on epidermal proliferation was significant at the doses of 2 micro g/g and 20 micro g/g, and that on epidermal differentiation was significant at the doses of 0.2 micro g/g or more. The effect of tacalcitol ointment (20 micro g/g) on epidermal differentiation was significantly stronger than tacalcitol ointment (2 micro g/g). In this study, tacalcitol ointment (20 micro g/g) was found to have a marked effect on cutaneous inflammation and improved effect on epidermal differentiation, although tacalcitol ointment (2 micro g/g) also had significant effects on epidermal proliferation and differentiation. These findings support the clinical effectiveness of tacalcitol ointment (20 micro g/g) against psoriasis.

Layer-by-layer oxidation of Si(001)-(2×1) surfaces was observed using the reflectance difference (RD) spectroscopy. Distinctive features in the RD spectra appeared near the E1 (3.3 eV) and E2 (4.2 eV) transition energies of Si. The polarity of these features was repeatedly reversed as the oxide thickness was increased to 4 monolayers (MLs). Oscillation of the RD amplitude near the E1 transition energy was observed in real time during the oxidation process. A half period of the oscillation corresponds to the oxidation of 1 ML. These results demonstrate the possibility of in situ counting and control of the number of oxidized layers.

Alendronate (alendronate sodium hydrate; Bonalon Tablet, 5 mg) is a nitrogen-containing bisphosphonate, which combines with the bone surface and reduces osteoclast-mediated bone resorption. It is a third-generation bisphosphonate compound, specifically distributed on the surface of bone resorption and taken into osteoclasts. Under the closed circumstances which is formed with osteoclast and the bone surface, alendronate becomes detached from the bone surface and taken into osteoclast since acid released from osteoclast leads to pH decrease (acidified). The uptaken alendronate blocks the pathway of mevalonic acid synthesis, which is cholesteric synthesis, inhibits the prenylation of GTP binding protein, and decreases the osteoclast's function by influencing the cytoskeleton. This restraint of alendronate in bone resorption against osteoclasts is reversible, showing no cytotoxicity at more than hundredfold concentration level at which action occurs. Alendronate is an agent for the treatment of osteoporosis that has established safety with regards to bone quality since it neither inhibits bone calcification nor influences fracture healing in chronic administration. The most serious morbidity in osteoporosis is developing fractures. The efficacy of alendronate on restraining fracture, as well as on increase in BMD, is evidenced in Japan. Recently, in addition to senile or postmenopausal osteoporosis, drug-induced osteoporosis, such as steroid-induced osteoporosis, has attracted attention. In this regard, alendronate has been found to be an effective agent for the treatment of osteoporosis overseas, being approved in over 90 countries and used by more than 4.5 million patients. This review will give an outline of alendronate, the preparation to have introduced a concept of Evidence Based Medicine earlier, from pharmacodynamic action to clinical efficacy.

We investigated the combined effects of alendronate and 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) on the bone mass and strength in aged ovariectomized rats and compared them with those of single treatments. Forty-week-old female rats underwent ovariectomy or sham operation, and after 15 weeks, ovariectomized rats were daily administered vehicle alone, alendronate (0.2 or 1.0 mg/kg,p.o.), 1alpha(OH)D3 (0.02 microg/kg, p.o.), or the combinations of 0.2 or 1.0 mg/kg of alendronate and 1alpha(OH)D3. After 12 weeks, the groups receiving combined treatments had significantly increased bone density and mechanical strength of the 4th lumbar vertebral body and the midfemur compared to the vehicle-treated group, and the effects were almost equal to or slightly less than the addition of those of the respective single treatments. The increase in mechanical strength was proportional to that in bone mineral density, suggesting that the stimulatory effects of these treatments on bone strength are ascribable primarily to those on bone mass. Analyses of histology, computed tomography, and biochemical markers confirmed the strong effect of the combined treatment on trabecular bone in particular, which was associated with increased trabecular number and decreased bone turnover. We propose that the combination of daily alendronate and 1alpha(OH)D3 is clinically promising as a curative treatment of established postmenopausal osteoporosis.

Interleukin (IL)-8, which is involved in inflammatory responses, is produced by a variety of cell types, monocytes/macrophages and neutrophils, in response to inflammatory stimuli including lipopolysaccha ride, IL-1, and tumor necrosis factor α. Here we report the inhibitory effects of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) on IL-8 production-dates printpubdate="05/03/02" in human whole blood culture. 1,25(OH)2D3 inhibited only the late phase of the biphasic IL-8 production-dates printpubdate="05/03/02" in lipopolysaccharide-stimulated human whole blood. It also effectively inhibited IL-8 production-dates printpubdate="05/03/02" induced by IL-1β compared with that induced by tumor necrosis factor α. IL-8 mRNA expression in IL-1β-stimulated whole blood was found to require de novo protein synthesis. Although monocytes were found to be mainly responsible for IL-1β-induced IL-8 production-dates printpubdate="05/03/02" in whole blood, 1,25(OH)2D3 inhibited IL-8 production-dates printpubdate="05/03/02...

Salmonella enterica subsp. enterica serovar Infantis strains were isolated from broiler chickens from six farms in Japan and the pathogenicity associated with the recently reported 280 kbp mega plasmid was examined by possession of the plasmid and histopathology of tissues from these chickens. S . Infantis strains were isolated from 10 of 24 chickens. Phylogenetic, network and Bayesian cluster analyses were used to determine whether these strains were in the previously defined Clusters 1–5. Phylogenetic analysis classified the strains isolated in this study in two groups (Groups A and B). Both groups contained strains from gastrointestional contents, but only Group A also contained strains from spleen, liver, and lymphoid tissues. Histopathology showed suppurative splenitis in a spleen from which Group A strains were isolated. Although network and Bayesian cluster analyses were unable to differentiate Group A and B strains from the previously defined Clusters 1–5, population genetic analysis indicated that Group A was a different population from Cluster 5, indicating that Group A would be a subpopulation of Cluster 5. The irp2 gene, which is in the mega plasmid carried by a pathogenic S . Infantis strain recently isolated in Israel, was found in both Groups A and B strains and in the previously reported Clusters 4 and 5 strains. These results suggested that Group A would be a novel subpopulation of the previously defined Cluster 5, and presence of the mega plasmid may not be related whether S . Infantis strains can infect certain organs.

Diabetic bone disease is characterized by low bone turnover resulting from impaired secretion of parathyroid hormone (PTH). However, it was suggested that the difference in duration of hemodialysis (HD) therapy and age of patients between HD patients with and without diabetes mellitus (DM) may be responsible for a significant reduction in serum intact PTH (iPTH) level in HD patients with DM. The present study showed that although such major factors affecting PTH secretion as age, sex, HD duration, and serum calcium, phosphate, and magnesium levels did not differ significantly between HD patients with and without DM, serum iPTH levels were still significantly lower in HD patients with than without DM. Among biochemical markers for bone metabolism, serum levels of intact osteocalcin (iOC) and deoxypyridinoline (DPD) were significantly lower in HD patients with than without DM, whereas serum bone-specific alkaline phosphatase, pyridinoline, and beta-crosslaps did not differ significantly between the two groups of patients. In summary, our findings indicate that PTH secretion may be significantly impaired in HD patients with DM compared with those without DM, and serum iOC and DPD are bone markers sensitive enough to detect low bone turnover in HD patients with DM.

The migration and adhesion of osteoblasts requires several classical cadherins. Cadherin-11, one of the classical cadherins, was expressed in mouse osteoblasts in skull bone and femur, revealed by immunohistochemistry. To elucidate the function of cadherin-11 in osteoblastogenesis, cadherin-11 null mutant mice were investigated. Although apparently normal at birth, Alizarin red staining of null mutant mice showed a reduced calcified area at the frontal suture that caused a round-shaped calvaria with increasing animal age to 3 months. Consequently, there was a reduction in bone density at the femoral metaphyses and the diploë of calvaria in null mutant mice. In the in vitro culture of newborn calvarial cells, the calcified area of mutant cells was smaller than those derived from wild-type littermates. These results show that absence of cadherin-11 leads to reduced bone density in some parts of skeletons including calvaria and long bone metaphyses, and thus suggest that cadherin-11 plays roles in the regulation of osteoblast differentiation and in the mineralization of the osteoid matrix.

The human epidermal keratinocyte cell line K-TL-1, developed from a benign epidermal tumor, was cultured in the presence of the synthetic vitamin D3 analogue tacalcitol [1α,24(R)-dihydroxyvitamin D3] to assess the effects on the production of nerve growth factor (NGF). Confluent K-TL-1 cells were cultured with 10–8M of tacalcitol. Supernatants and cell homogenates were collected and NGF concentrations were determined by enzyme-linked immunosorbent assay. The concentration of NGF in the supernatants of cultures treated with tacalcitol peaked within 24 h after the start of tacalcitol treatment and remained stable for 96 h. This NGF induction caused by tacalcitol was dose-dependent, showing an ED50 between 10–10 and 10–9M. Induction of NGF mRNA expression by tacalcitol was also observed by RT-PCR, indicating that tacalcitol induced NGF expression through transcriptional activation. These results suggest that active vitamin D3 could treat peripheral neuropathy by inducing NGF production in the skin.

It has been reported that osteopontin (OPN) plays an important role during urolithiasis as well as bone formation. Generation of stones in the urinary tract may be associated with osteoporosis and bisphosphonates are potent inhibitors of bone resorption, being used with effect in the management of bone disease. We therefore investigated the relationship between alendronate, a bisphosphonate derivative, and OPN expression in the kidney. Alendronate was administered to rats made hypercalcemic by treatment with parathyroid hormone-related peptide (PTHrP). The renal expression of OPN was then evaluated at both protein and mRNA levels. OPN expression was enhanced in the distal tubular cells of hypercalcemic rats and was decreased by alendronate. The observed inhibition of OPN expression suggests an ability of alendronate and other bisphosphonates to act as inhibitors of stone formation in the urinary tract.

1 The production of chemokines, RANTES and IL-8 in cultured human dermal fibroblasts and the effects of tacalcitol (1α,24(R)-dihydroxyvitamin D3) were studied using an enzyme-linked immunosorbent assay. 2 In the unstimulated condition, RANTES and IL-8 were at a trace level in the culture supernatant. On stimulation with TNF-α alone for 24 h, RANTES and IL-8 production were induced. Tacalcitol suppressed RANTES and IL-8 production dose-dependently at concentrations between 10−12m and 10−7m. 3 When the cells were treated with TNF-α and IFN-γ in combination, RANTES production was enhanced, but IL-8 production was not changed, compared to TNF-α-treated cells. Tacalcitol decreased IL-8 production dose-dependently as observed in the TNF-α-treated cells. On the other hand, RANTES production was enhanced by 10−11m and 10−10m of tacalcitol, and dose-dependently suppressed by tacalcitol concentrations higher than 10−9m. 4 Active vitamin D3 compounds, betamethasone valerate and cyclosporin A were compared with respect to their effects on chemokine production. Three active vitamin D3 compounds, tacalcitol, 1α,25-dihydroxyvitamin D3 and MC903 (calcipotriol), inhibited the production of RANTES and IL-8, with very similar potencies. Betamethasone valerate also inhibited these chemokine productions, but with greater potency than active vitamin D3 compounds. Cyclosporin A significantly stimulated RANTES production at 10−6m and IL-8 production at 10−7m and 10−6m. 5 The results of this study suggest that active vitamin D3 compounds exert some beneficial effects in the treatment of inflammatory skin diseases via regulation of the production of chemokines by dermal fibroblasts. British Journal of Pharmacology (1998) 124, 1433–1438; doi:10.1038/sj.bjp.0701988

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is thought to be an important systemic factor in the fracture repair process, but the mechanism of action of 1,25(OH)2D3 has not been clearly defined. In this study, the role of 1,25(OH)2D3 in the fracture repair process was analyzed in a rat closed femoral fracture model. The plasma concentration of 1,25(OH)2D3 rapidly decreased on day 3 and continued to decrease to 10 days after fracture. We assessed whether this decrease was based on the accelerated degradation or retardation of the synthesis rate of 1,25(OH)2D3, from 25(OH)D3. After radiolabeled 3H-1,25(OH)2D3 or 3H-25(OH)D3 was injected i.v. into fractured or control (unfractured) rats, the concentrations of 25(OH)D3 and 1,25(OH)2D3 metabolites were measured by HPLC. The plasma concentrations of these radiolabeled metabolites in fractured group were similar to those in control rats early after operation. However, radioactivity in the femurs of fractured rats was higher than that of the control group. Furthermore, the radioactivity was concentrated in the callus of the fractured group analyzed by autoradiography. 1,25(OH)2D3 receptor gene expression was detected early after fracture and, additionally, both in the soft and hard callus on days 7 and 13 after fracture. These results showed that the rapid disappearance of 1,25(OH)2D3 in the early stages after fracture was not due to either increased degradation or decreased synthesis of 1,25(OH)2D3, but rather to increased consumption. Further, these results suggest the possibility that plasma 1,25(OH)2D3 becomes localized in the callus and may regulate cellular events in the process of fracture healing.

The barrier properties of W, W2N and WN layers to prevent intermixing of Cu wiring with the Si substrate were investigated. W, W2N and WN barrier layers 25 nm thick were found to prevent intermixing after annealing at 650, 790 and 500°C for 30 min, respectively. W2N, which showed the best barrier property, had a polycrystalline structure with disordered grain boundaries, and Cu diffusion in W2N was concluded to be controlled by grain boundaries of the W2N layer based on the diffusional analysis of Cu in W2N.

In normal rats given alendronate (0.01-6.25 mg/kg) or elcatonin (synthetic eel calcitonin; 0.32-8.0 U/kg), changes in urinary calcium (Ca), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) excretion during the hypocalcemic response were assessed. Although the lower doses (0.01-0.25 mg/kg) of alendronate did not influence plasma Ca, the high doses (1.25-6.25 mg/kg) significantly decreased plasma Ca by the third day after single iv administration. In these groups, urinary Ca excretion did not show any significant change, but urinary Pyr and D-Pyr excretion decreased significantly at high doses. The hypocalcemic effect lasted for only 1 or 2 days (2-3 days after injection) even at high doses of alendronate. In the group receiving elcatonin (8.0 U/kg, twice daily), a significant decrease in plasma Ca was evident as early as 1 day after the start of administration. This was accompanied by a marked increase in urinary Ca excretion in the early stage without a significant decrease in urinary Pyr or D-Pyr excretion, and the suppression of bone resorption was more pronounced in the late phase of treatment with elcatonin. These results suggest that alendronate decreases plasma Ca chiefly by suppressing bone resorption, whereas elcatonin decreases plasma Ca by inhibiting bone resorption and accelerating Ca excretion. The present data show that both alendronate and elcatonin inhibit bone resorption and exert an antihypercalcemic effect, but the mechanism of action is different in the two drugs.

The metallization process for the chemical vapor deposition of aluminum from dimethylaluminumhydride [(Al(CH3)2H, DMAH)] has received considerable attention. In this article, the authors discuss the vaporization of DMAH, Al deposition kinetics, selective growth, and film properties. Although DMAH has extremely high viscosity (about 4000 cP), it was found by metering the DMAH flow rate that DMAH can be vaporized while maintaining a high efficiency of 80%–100 % of the theoretical flow rate, even with the conventional bubbling method. The film growth rate followed the Arrhenius law at lower temperatures (

Pyridinoline (Pyd) and deoxypyridinoline (D-pyd), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography (HPLC) in urine samples from 17 male control subjects and 17 male lung cancer patients either with or without bone metastases. Ten patients with bone metastases had significantly higher (P < 0.01) urine concentrations of Pyd and D-pyd than did control subjects. No cross-link increase was seen in seven lung cancer patients without clinically detectable bone metastases. We also measured contemporaneously urinary hydroxyproline (OH-Pro) and serum alkaline phosphatase (ALP). We found higher concentrations of OH-Pro and ALP in patients with metastatic lung cancer compared to those with nonmetastatic lung cancer or control subjects. There was a significant correlation among pyridinium cross-links, OH-Pro, and ALP. In addition, the excretion of pyridinium cross-links in lung cancer with metastases correlated directly with bone scan Soloway scores (rs = 0.74,P = 0.02;rs = 0.67,P = 0.03, respectively), whereas levels of OH-Pro and the ALP level did not (rs = 0.52,P = 0.07 andrs = 0.50,P = 0.13, respectively). These findings suggest that the measurement of Pyd and D-pyd in urine may be used to quantitate bone metastases in lung cancer.

A monoclonal antibody (10B) against the N-terminal sequence of human osteocalcin was selected to characterize its epitope and species specificity. The cross-reactivity of 10B with human and rat osteocalcin demonstrated that the reactivities of 10B with both human and rat osteocalcins were very similar. The pin technology method was used to determine the epitope and clearly demonstrated that the epitope recognized by 10B was localized to residues 12–16, the sequence of which is identical in rat and human osteocalcin molecules. This monoclonal antibody was found to be useful for designing region-specific sandwich immunoassay systems for human and rat N-terminal osteocalcin (N-OC) molecules using rabbit anti-hN20 and anti-rN20 polyclonal antibodies, respectively. The osteocalcin levels in serum determined by this N-OC method were stable during prolonged storage at 25°C and the method could be usefully applied in the development of immunoassay systems for many osteocalcin molecules from many other species.

Spin-on glass (SOG) coating solutions containing various amount of Si-CH 3 were synthesized by hydrolytic polymerization from monomers of tetramethoxysilane and methyltrimethoxysilane. Film properties of the SOG film formed from the synthesized coating solutions were evaluated as a function of Si-CH 3 concentration. The film shrinkage linearly decreased with the Si-CH 3 content, and it became zero when the Si-CH 3 concentration was 100%. Water absorption as well as dielectric constant of the film decreased with increasing S:i-CH 3 content. Fourier transform infrared spectroscopy showed that this tendency can be attributed to the decrease of Si-OH content, which decreased with an increase of Si-CH 3 content. Si-OH in SOG film causes a high shrinkage of the film due to its heat-induced polycondensation. Si-OH is also the origin of a high dielectric constant and water absorption because of its high polarization. Therefore, SOG with a high organic content is preferred

Seven kinds of commercially available organic spin-on glass (SOG) were evaluated and analyzed to reveal a relationship between film properties and their chemical composition. Film properties evaluated were shrinkage, refractive index, wet/dry etching rates, and adhesion strength. The structure of SOG solute was analyzed by 29 SSi-nuclear magnetic resource (NMR) spectroscopy. Composition of the solution was assayed in terms of GC-MS as well as 1 H- and 13 C-NMR. The properties were widely distributed among seven SOG films, which could be explained on the basis of the concentration of Si-C direct bond in the solute calculated from 29 Si-NMR spectroscopy. Important parameters corresponding to the film quality such as film shrinkages, wet and dry etching rates decreased, with an increase of Si-C direct bonding. From this point of view, SOG solute having a high organic content is favorable for forming film with high cracking resistance and good planarization of the underlayer topology. The composition of the solvent appears to affect the viscosity of the solution, which dominates the properties during coating such as occurrence of striation or film thickness per coat