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The optimal duration of antibiotic treatment has not been established for pneumonia patients. Some investigators reported procalcitonin (PCT)-guided antimicrobial stewardship reduces the duration of antibiotic use without increasing mortality in pneumonia patients.We prospectively enrolled hospitalized community-acquired pneumonia or healthcare-associated pneumonia patients with PCT levels0.20 ng/mL on admission, who were admitted between 2014 and 2017. PCT levels were measured on days 5, 8 and 11 and every 3 days thereafter if needed. Physicians were encouraged and strongly encouraged to discontinue antibiotics when PCT levels decreased below 0.20 ng/mL and 0.10 ng/mL, respectively. Those admitted between 2010 and 2014 were included in the study as historical controls. Primary endpoints were duration of antibiotic treatment and recurrence of pneumonia within 30 days after antibiotic discontinuation.The PCT-guided and control groups consisted of 116 patients each. Background factors including pneumonia severity and PCT levels did not differ between the 2 groups. Median duration of antibiotic treatment was 8.0 and 11 days in the PCT-guided and control groups, respectively (P0.001). Multivariable regression analysis revealed that PCT-guided antibiotic discontinuation (partial regression coefficient [PRC] -1.9319, P0.001), PCT (PRC 0.1501, P = 0.0059) and albumin (PRC -1.4398, P = 0.0096) were significantly related to duration of antibiotic treatment. Pneumonia recurrence within 30 days after antibiotic discontinuation was not statistically different between the 2 groups (4.3% vs. 6.0%, P = 0.5541).PCT-guided antibiotic discontinuation might be useful for shortening the duration of antibiotic treatment without increasing pneumonia recurrence.

Introduction It is not uncommon for patients hospitalized with pneumonia to experience an early relapse. Here, we investigated the factors related to pneumonia recurrence in Japan. Purpose We aimed to elucidate the factors related to early recurrence after completion of pneumonia treatment. Methods We examined 696 patients with community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP) who were admitted to our hospital between October 2010 and February 2018, excluding those who died during hospitalization. Logistic regression analysis was used to assess the endpoint of recurrence within 30 days after the end of antibiotic treatment. Results NHCAP, chronic lung disease and duration of antibiotic treatment were significant risk factors for recurrence of pneumonia within 30 days after antibiotic discontinuation. Aspiration pneumonia was not be a significant factor in the early recurrence of pneumonia. Conclusions Long-term use of antimicrobials may be a risk factor in early recurrence of pneumonia.

Background Small-bore aspiration catheters (Aspiration Kit®) cause less pain than conventional trocar catheters in patients. The objective of this study was to examine the usefulness of these less invasive small-bore aspiration catheters for drainage of pneumothorax. Methods Baseline characteristics and laboratory test data at admission of 70 patients who were admitted to and underwent drainage treatment for pneumothorax at our hospital between April 2011 and February 2017 were retrospectively reviewed based on their medical records. The primary endpoints were factors associated with drainage treatment failure, and baseline characteristics and laboratory test data were compared between those treated with a small-bore aspiration catheter and those treated with a trocar catheter. Results The numbers of patients with anticoagulant use (P

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Lessons Learned Alectinib confers a pronounced survival benefit in patients with ALK rearrangement-positive non-small cell lung cancer and a poor performance status. Survival benefit of alectinib for patients with a poor performance status was consistent regardless of the presence of central nervous system metastases. Background We previously reported a marked objective response rate (ORR) and safety for alectinib treatment in patients with ALK rearrangement-positive non-small cell lung cancer (NSCLC) and a poor performance status (PS) in the Lung Oncology Group in Kyushu (LOGiK) 1401 study. It remained unclear, however, whether alectinib might also confer a long-term survival benefit in such patients. Methods Eighteen patients with ALK rearrangement-positive advanced NSCLC and a PS of 2, 3, or 4 (n = 12, 5, and 1, respectively) were enrolled in LOGiK1401 between September 2014 and December 2015 and received alectinib. We have now updated the survival data for the study. Results The median follow-up time for all patients was 27.3 months. The median progression-free survival (PFS) was 16.2 months (95% confidence interval [CI], 7.1–30.8 months), and the median survival time (MST) and the 3-year overall survival rate were 30.3 months (95% CI, 11.5 months to not reached) and 43.8% (95% CI, 20.8–64.7%), respectively. This survival benefit was similarly manifest in patients with a PS of 2 (MST, 20.5 months) and those with a PS of ≥3 (MST, not reached). PFS did not differ between patients with or without central nervous system (CNS) metastases at baseline (median of 17.5 and 16.2 months, respectively, p = .886). Conclusion Alectinib showed a pronounced survival benefit for patients with ALK rearrangement-positive NSCLC and a poor PS regardless of the presence of CNS metastases, a patient population for which chemotherapy is not indicated.

Phosphatidylserine (PS) has skewed distributions in the plasma membrane and is preferentially located in the inner leaflet of normal cells. Tumour cells, however, expose PS at the outer leaflet of cell surfaces, thereby potentially modulating the bio-signalling of cells. Interestingly, exosomes – or, more properly, small extracellular vesicles (sEVs) – which are secreted from tumour cells, are enriched with externalized PS, have been proposed as being involved in the progression of cancers, and could be used as a marker for tumour diagnostics. However, the sEV fractions prepared from various methods are composed of different subtypes of vesicles, and knowledge about the subtypes enriched with exposed PS is still limited. Here, we differentiated sEVs from cancer cell lines by density gradient centrifugation and characterized the separated fractions by using gold-labelling of PS in atomic force microscopy, thrombin generation assay, size and zeta potential measurements, and western blot analysis. These analyses revealed a previously unreported PS+-enriched sEV subtype, which is characterized by a lower density than that of canonical exosomes (1.06 g/ml vs. 1.08 g/ml), larger size (122 nm vs. 105 nm), more negative zeta potential (−28 mV vs. −21 mV), and lower abundance of canonical exosomal markers. The identification of the PS-exposed subtype of sEVs will provide deeper insight into the role of EVs in tumour biology and enhance the development of EV-based tumour diagnosis and therapy.

Background Procalcitonin (PCT) is a useful marker for pneumonia. However, its clinical usefulness in elderly patients has not been studied extensively. This study aimed to assess the relationship between PCT and prognosis and pneumonia severity in elderly patients with pneumonia acquired outside the hospital. Methods Data considered relevant to pneumonia severity and prognosis were retrospectively obtained from clinical charts of all patients with pneumonia who were admitted to our hospital from 2010 to 2017. The primary outcome was 30-day mortality in elderly patients (aged ≥75 years), and the relationship between PCT levels and pneumonia severity, as determined by the pneumonia severity index (PSI) was also examined. Results Data were collected from 667 patients, of which 436 were elderly patients. Multivariate and receiver operating characteristic curve analysis revealed that albumin, body mass index, and PSI class rather than PCT are important factors related to 30-day mortality in elderly patients. PCT was also not an independent prognostic factor in younger patients. PCT levels significantly differed by pneumonia severity (mild, moderate, and severe) in both younger (p

Small-bore aspiration catheters (Aspiration KitBaseline characteristics and laboratory test data at admission of 70 patients who were admitted to and underwent drainage treatment for pneumothorax at our hospital between April 2011 and February 2017 were retrospectively reviewed based on their medical records. The primary endpoints were factors associated with drainage treatment failure, and baseline characteristics and laboratory test data were compared between those treated with a small-bore aspiration catheter and those treated with a trocar catheter.The numbers of patients with anticoagulant use (P0.0001), ischemic stroke (P = 0.0063), and atrial fibrillation (P = 0.0410) were significantly different between the two groups. No significant intergroup differences were noted with respect to the length of hospitalization, drainage duration, subcutaneous emphysema, and treatment failure. Logistic regression analyses of baseline characteristics showed that the severity of pneumothorax, localization of pneumothorax, and recurrent pneumothorax were significantly associated with drainage treatment failure, but the type of drainage catheter was not significantly associated with treatment failure. [Conclusions] The results suggest that small-bore aspiration catheters, which cause less pain in patients, are potentially useful for pneumothorax drainage.

This study examined the clinical significance of intra-alveolar fibrin deposition (IAFD) in transbronchial lung biopsy specimens obtained from patients with organizing pneumonia. Pathological reports of transbronchial lung biopsies performed between 2004 and 2012 were reviewed to identify cases of intra-alveolar organization with or without fibrin deposition. Clinical charts, computed tomography images, and transbronchial lung biopsy specimens from these cases were examined retrospectively. Diagnosis of organizing pneumonia was reevaluated based upon the consensus of a respiratory physician, a radiologist, and a pathologist. Transbronchial lung biopsy results of the reviewed patients with organizing pneumonia found seven patients who had IAFD, and 34 who did not. Seven patients’ conditions were associated with collagen vascular disease (CVD), and 34 were cryptogenic. IAFD was significantly associated with high C-reactive protein (CRP) values (>5 mg/dl) (p = 0.0012) and underlying CVD (p = 0.0099). Multivariate analysis revealed that IAFD was independently associated with high CRP values (p = 0.0184). Three of 31 patients and six of 27 patients experienced a relapse of organizing pneumonia within 6 months and 1 year, respectively. IAFD (p = 0.0044) and high CRP values (p = 0.0207) were significantly related to relapse within 6 months, while only CRP was significantly related to relapse within 1 year (p = 0.0007). In patients with organizing pneumonia, IAFD was significantly associated with high CRP values. High CRP values and/or IAFD predicted relapse of organizing pneumonia within 6 months to 1 year.

Background: Differentiating cryptogenic organizing pneumonia (COP) from community-acquired pneumonia (CAP) can be difficult in some cases. Objective: To clarify the clinical utility of procalcitonin (PCT) levels for differentiating between COP and CAP. Methods: Blood PCT levels, leukocyte count, C-reactive protein concentration, number of segments involved on computed tomography (CT) images, and pneumonia severity assessment scale were retrospectively investigated from clinical charts and chest CT images of COP and CAP patients who were admitted to our hospital from 2012 to 2014. The clinical characteristics of COP patients were compared to those of CAP patients for whom causative organisms were not detected. Results: There were 16 COP and 94 CAP patients for whom causative organisms were not detected. Blood PCT levels of all COP patients were less than 0.16 ng/dL, and significantly lower than those of CAP patients (p = 0.0004), while the number of involved segments was significantly higher than that of CAP patients (p = 0.0001). Blood PCT levels and the number of involved segments remained independently significant for differentiating between COP and CAP by multivariate analysis. Receiver operating characteristics curve analysis revealed that 7 was the best cut-off number for involved segments to differentiate between COP and CAP patients with low PCT levels (sensitivity 85.7%, specificity 94.7%). Conclusion: A combination of PCT levels and number of involved segments on CT images is useful for differentiation between COP and CAP.

Purpose This study aimed to elucidate factors related to 30-day mortality of pneumonia occurring outside hospital by comprehensively analyzing data considered relevant to prognosis. Methods Data considered relevant to prognosis were retrospectively examined from clinical charts and chest X-ray images of all patients with pneumonia occurring outside hospital admitted to our hospital from 2010 to 2016. The primary outcome was 30-day mortality. Results Data were collected from 534 patients (317 community-acquired pneumonia and 217 nursing- and healthcare associated pneumonia patients; 338 men (63.3%); mean age, 76.2 years-old). Eighty-three patients (9.9%) died from pneumonia within 30 days from the date of admission. The numbers of patients with pneumonia severity index (PSI) classes of I/II/III/IV/V and age, dehydration, respiratory failure, orientation disturbance, pressure (A-DROP) scores of 0/1/2/3/4/5 were 29/66/127/229/83, and 71/107/187/132/30/7, respectively. Mean (standard deviation) body mass index (BMI), serum albumin, blood procalcitonin, white blood cell and C-reactive protein were 20.00 (4.12) kg/m2, 3.16 (0.60) g/dL, 3.69 (13.15) ng/mL, 11559.4 (5656.9)/mm3, and 10.92 (8.75) mg/dL, respectively. Chest X-ray images from 152 patients exhibited a pneumonia shadow over a quarter of total lung field. Logistic regression analysis revealed that PSI class or A-DROP score, BMI, serum albumin, and extent of pneumonia shadow were related to 30-day mortality. Receiver operating characteristics curve analysis revealed that serum albumin was superior to PSI class or A-DROP score for predicting 30-day mortality. Conclusion Serum albumin is not less important than PSI class or A-DROP score for predicting 30-day mortality in hospitalized patients with pneumonia occurring outside hospital.

A microcapillary chip-based particle electrophoresis system developed for characterizing extracellular vesicles (EVs) is described. So far, it is technologically difficult to analyze or identify a heterogeneous population of particles ranging from several tens to one hundred nanometers, and hence, there is a growing demand for a new analytical method of nanoparticles among researchers working on extracellular vesicles. The analytical platform presented in this chapter allows detection of individual nanoparticles or nanovesicles of less than 50 nm in diameter and enables the characterization of nanoparticles based on multiple indexes such as concentration, diameter, zeta potential, and surface antigenicity. This platform will provide a useful and easy-to-use solution for obtaining both quantitative and qualitative information on EV samples used in research and development of exosome biology and medicine.

A microcapillary chip-based particle electrophoresis system developed for characterizing extracellular vesicles (EVs) is described. So far, it is technologically difficult to analyze or identify a heterogeneous population of particles ranging from several tens to one hundred nanometers, and hence, there is a growing demand for a new analytical method of nanoparticles among researchers working on extracellular vesicles. The analytical platform presented in this chapter allows detection of individual nanoparticles or nanovesicles of less than 50 nm in diameter and enables the characterization of nanoparticles based on multiple indexes such as concentration, diameter, zeta potential, and surface antigenicity. This platform will provide a useful and easy-to-use solution for obtaining both quantitative and qualitative information on EV samples used in research and development of exosome biology and medicine.

We investigated the role of interferon regulatory factor 8 (IRF8) in a model of chronic pain in which repeated cold stress (RCS) exposure produces tactile allodynia. RCS exposure produced a decrease in paw withdrawal threshold (PWT) to mechanical stimulation. Spinal microglia of RCS-exposed mice were morphologically activated. Expression of IRF8 was significantly increased in the spinal cord of RCS-exposed mice and was localized in microglia. IRF8-knockout mice failed to show the RCS-induced decrease in PWT. Thus, RCS exposure activates spinal microglia and upregulation of IRF8 in these cells is involved in the development of tactile allodynia after RCS exposure. Keywords:: interferon regulatory factor-8, microglia, repeated cold stress

Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca2+ signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.

Background: Patients with inflammatory bowel disease (IBD) occasionally present with pulmonary involvement. Recently, a tumor necrosis factor-α (TNF-α) blocking agent was introduced for the treatment of IBD in Japan. We aimed to clarify the frequency and type of chest X-rays or computed tomography (CT) abnormalities associated with IBD in patients treated with infliximab (IFX). Methods: We prospectively obtained, through interviews, information regarding respiratory symptoms, medical history, smoking history, occupational and environmental exposure, and medication history for patients with IBD treated with IFX at the IBD center of our hospital. We also examined percutaneous oxygen saturation (SpO2) and chest X-rays. Chest computed tomography and spirometry were also performed for patients with respiratory symptoms, abnormal SpO2, and/or abnormal chest X-rays. Results: Subjects were 115 patients with Crohn’s disease (CD) and 8 with ulcerative colitis (UC). Of those with CD, 21 presented with respiratory symptoms. Among these, 4 (3.5%) had chest X-ray abnormalities. None of the patients with UC had respiratory symptoms or chest X-ray abnormalities. CT examination of 13 patients with CD revealed 5 with bronchiectatic changes, ground glass opacity (GGO), consolidation, nodular lesions, and/or granular shadows. Conclusion: Chest X-rays or computed tomography abnormalities were detected in at least 3.5% of patients with CD treated with IFX.

Electrophoretic mobility (EPM) of human promyelocytic leukemia cell lines (HL60) during neutrophil differentiation induced by all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO) was measured using microcapillary electrophoresis chips. Prior to EPM measurement of HL60 cells, neutrophil differentiation of the cells was confirmed by morphological classification. Subsequently, EPM of HL60 cells was measured using an on-chip cell electrophoresis system before and after neutrophil differentiation. The EPM changed gradually with the progress of the neutrophil differentiation. From the analysis of experimental data by principal component analysis, it was revealed that there is a strong correlation between morphologic classification and EPM during the neutrophilic differentiation. The present result suggests that on-chip EPM measurement system can be used as a monitoring tool for the cell differentiation.

Two patients with granulomatous lung lesions thought to be related to Crohn's disease (CD) are reported. Patient 1 was a 43-year-old man who was diagnosed with CD at age 11 years. He developed a fever in the 38 °C, and a chest X-ray and CT scan showed infiltrates with air bronchograms in the right upper lobe and left lingular segment. Transbronchial lung biopsy (TBLB) revealed granulomatous lesions. Patient 2 was a 76-year-old woman who was diagnosed with CD at age 44 years. Chest CT showed infiltrates and nodular shadows in both lung fields. Video-assisted thoracoscopic surgery (VATS) in June 2012 revealed granulomatous lesions. Tuberculosis, fungal infections, drug-induced lung disorder, and sarcoidosis were ruled out as a cause of the granulomatous lesions in both patients. The aetiology was thought to be CD.

The amorphous perfluoropolymer CytopTM (Asahi Glass Co., Ltd.) is an attractive material for use in microdevices for biological and chemical analysis because of its high optical transparency, excellent chemical stability, and low refractive index of 1.34, which is almost the same as that of water. In this study, to increase the applicability of this polymer for such microdevices, the modification of its surface properties was investigated using low-pressure argon plasma. Hydrophilicity control with a water contact angle in the range from 30° to 110° and, moreover, the long-term stability of the hydrophilized surface were achieved for the first time. Although oxygen plasma treatment caused etching instead of hydrophilization, exposure to argon plasma led to bond breaking, the formation of free radicals, and finally the incorporation of hydrophilic groups as a result of the reaction with the oxygen or water from the atmosphere after the polymer was removed from the plasma reactor. Furthermore, to evaluate the suitability of this material for applications involving cell cultivation, the cell adhesion and proliferation properties of the plasma-treated surface were also investigated.

In clinical practice, glucocorticoids are often used with the aim of modulating the efficacy and toxicity of chemotherapeutic agents. However, how glucocorticoids modulate the pharmacological action of chemotherapeutic agents remains to be clarified. In this study, we generated glucocorticoid receptor (GR)-deficient rat-1 cells to investigate the role of GR in the regulation of cellular sensitivity to irinotecan hydrochloride (CPT-11). Treatment of wild-type rat-1 cells with dexamethasone (DEX) significantly enhanced the cytotoxic effect of CPT-11, whereas the treatment had little effect on the cytotoxicity of CPT-11 in GR-deficient cells. Topoisomerase-I activity in wild-type cells after concomitant treatment with DEX and CPT-11 was significantly lower than that after treatment with CPT-11 alone. DEX treatment also enhanced the inhibitory action of CPT-11 on the phosphatidylinositol 3-kinase–Akt signaling pathway in wild-type cells, accompanied by facilitating caspase-3 activity. These modulatory effects of DEX on the CPT-11–induced cytotoxicity were not observed in GR-deficient cells. Our present findings reveal the underlying mechanism by which GCs enhance the chemotherapeutic effect of CPT-11 and indicate the possibility that the dosage of CPT-11 could be reduced by the combination treatment with GCs, which may attenuate the adverse effect without decreasing anti-tumor activity.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.08219FP] Keywords:: glucocorticoid receptor, dexamethasone, CPT-11, topoisomerase-I, phosphatidylinositol 3-kinase [PI(3)K]–Akt signaling

The application of on-chip cell electrophoresis to the diagnosis of cell damage after treatment with a cell dissociation agent has been studied for the first time using both floating and adherent cells. First, a preliminary experiment was carried out using HL-60 (human leukemic) cells in order to investigate how cell dissociation agents affect the cell surface. After the treatment of HL-60 cells with three different cell dissociation agents for 20 min, the effects of cell dissociation agents on the cell were examined by both biological and electrical approaches. The result of an on-chip electrophoresis experiment showed the possibility of detecting a slight change in HL-60 cell surfaces, while no significant changes were observed by biological methodologies. The largest effect was particularly observed for trypsin treatment. Subsequently, the effects of trypsin treatment time were investigated using HeLa cells as an example of adherent cells. As a result, both biological and electrical measurements showed an increasing variation of the cells with trypsin treatment time. Thus, it is considered that the possible application of an on-chip cell electrophoretic mobility measurement system for the noninvasive evaluation of cell state that does not include cell labeling or mechanical damage after cell dissociation agent treatment. Such a system is expected to be valuable for the quality control of sample cells that will be required in future cell-based biotechnology applications.

A scanning radical microjet (SRMJ) equipment using oxygen microplasma has been developed and successfully applied for controlling biological cells’ attachment on biocompatible polymer material, poly(dimethylsiloxane) (PDMS). The radical microjet has advantages in localized and high-rate surface treatment. Moreover, maskless hydrophilic patterning using SRMJ has been demonstrated to be applicable to patterned cell cultivation which is useful in emerging biotechnological field such as tissue engineering and cell-based biosensors. Since control of PDMS surface properties is an indispensable prerequisite for cells’ attachment, effects of oxygen flow rates and treatment time on localized hydrophilic patterning of PDMS surfaces were first investigated for controlling HeLa cells’ (human epitheloid carcinoma cell line) attachment. Relationships between surface conditions of treated PDMS films and attached cell density are also discussed based on surface properties analyzed using atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS).

Microarray chip technology such as DNA chips, peptide chips, and protein chips is one of the promising approaches for achieving high-throughput screening (HTS) of biomolecule function since it has great advantages in feasibility of automated information processing due to one-to-one indexing between array position and molecular function as well as massively parallel sample analysis as a benefit of downsizing and large-scale integration. Mostly, however, the function that can be evaluated by such microarray chips is limited to affinity of target molecules. In this paper, we propose a new HTS system and enzymatic activity based on microreactor array chip technology. A prototype of the automated and massively parallel measurement system for fluorometric assay of enzymatic reactions was developed by the combination of microreactor array chips and a highly sensitive fluorescence microscope. Design strategy of microreactor array chips and an optical measurement platform for the high-throughput enzyme assay are discussed. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 92(4): 35–41, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10056

UTokyo Research掲載「載せるだけで細胞の酸素消費量を測定できるシート型センサ」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/flexible-sheet-type-sensor-for-measuring-cellular-oxygen-metabolism.html, UTokyo Research "Flexible sheet-type sensor for measuring cellular oxygen metabolism" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/flexible-sheet-type-sensor-for-measuring-cellular-oxygen-metabolism.html

Electrical characteristics of biological cells are important indices for obtaining information about the state and function of a cell. In this paper, we report the development of microdevices for physioelectrical measurement of cells by applying nano/microfabrication technologies. These devices enable the highly precise measurement of cell membrane potential and zeta potential of individual cells in a minimally invasive manner. Such a fusion of the microdevice technologies and biotechnologies is expected to provide power diagnostic tools for future cell study and cell therapy. © 2008 Wiley Periodicals, Inc. Electron Comm Jpn, 91(1): 40– 45, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10027

A scanning microjet treatment (SMJ) using nitrogen radicals was developed and applied it for controlling biological cells' attachment on biocompatible polymer material, poly(dimethylsiloxane) (PDMS). Previously, we developed an atmospheric-pressure argon/oxygen (Ar/O2) radical microjet system and used it for modifying PDMS surface. In this study, we examined argon/nitrogen (Ar/Nsub>2) plasma system and compared it with the previous study using Ar/O2 system in terms of degree of hydrophilicity, chemical state, surface morphology and cell adhesion. The results from the Ar/N2 system showed interesting phenomena that indicate promising potentials for application in controlling cell adhesion.

背景. Gefitinibは化学療法による既治療が奏効しなかった肺腺癌患者に投与されるが, 下痢などの有害事象はこれらの患者にとって深刻な問題となる. 症例. 71歳女性. 2002年2月に肺腺癌 (臨床病期IIIB) と診断した. プラチナ製剤を含む化学療法を行ったが無効であったので, gefitinib 250 mg/日の投与を行った. 重篤な下痢が出現したために塩酸ロペラミドを投与し, 7日間休薬した後, 隔日投与にて治療を再開した. その結果, 下痢は止まり腫瘍の縮小率は44% (RECIST) に達しPRと判定した. 結論. 現在までに, 国内外ともに隔日投与により, 重篤な副作用を回避し臨床効果をあげられた報告はなく, 今後は隔日投与の体内動態を再検討し, 他の内服方法と比較することで臨床効果のみならず, 有益な経済効果をもたらす可能性があると考えられた.

Influence of hydroxyurea (HU) on the antitumor effect of irinotecan hydrochloride (CPT-11) was investigated in ICR male mice transplanted with sarcoma 180 cells (S-180). A single dose of CPT-11 (100 mg/kg) was injected at various times after a single dose of HU (300 mg/kg). The relative tumor weight varied significantly depending on the timing of CPT-11 injection after HU injection (P < 0.01). The higher antitumor effect of CPT-11 was observed when DNA synthesis of S-180 cells increased (20 hr), and the lower effect was observed when the DNA synthesis decreased (0 hr). The loss of body weight also varied significantly depending on the timing of CPT-11 injection after HU injection (P < 0.01). The toxicity of CPT-11 was higher when the inhibitory effect of HU on DNA synthesis of bone marrow cells was stronger (15 hr), and the lower toxicity was observed when the inhibitory effect was not observed (0 hr). The plasma SN-38 concentration at 2 hr after CPT-11 injection was higher at 20 hr after HU injection than at 0 hr after HU injection. The difference in plasma esterase activity between 0 hr and 20 hr after HU injection was regarded as the mechanism underlying the dosing time-dependent difference of the SN-38 concentration. These experiments suggest that HU can produce a different phase of cell cycle between tumor cells and normal cells. This leads to increase the antitumor effect of CPT-11 without increasing the adverse effect of the drug. It is essential to consider the dosing time in the two-drug combination therapy.

The high-resolution imaging of neural cells in vivo has brought about great progress in neuroscience research. Here, we report a novel experimental platform, where the intact brain of a living mouse can be studied with the aid of a surgically implanted micro-optical fluidic device; acting as an interface between neurons and the outer world. The newly developed device provides the functions required for the long-term and high-resolution observation of the fine structures of neurons by two-photon laser scanning microscopy and the microfluidic delivery of chemicals or drugs directly into the brain. A proof-of-concept experiment of single-synapse stimulation by two-photon uncaging of caged glutamate and observation of dendritic spine shrinkage over subsequent days demonstrated a promising use for the present technology.