Search

// Marie Shimanuki 1 , Yorihisa Imanishi 1 , Yoichiro Sato 1 , Nana Nakahara 1 , Daisuke Totsuka 1 , Emiri Sato 1 , Sena Iguchi 1 , Yasuo Sato 2 , Keiko Soma 3 , Yasutomo Araki 1 , Seiji Shigetomi 4 , Satoko Yoshida 5 , Kosuke Uno 6 , Yusuke Ogawa 7 , Takehiro Tominaga 5 , Yuichi Ikari 5 , Junko Nagayama 4 , Ayako Endo 8 , Koshiro Miura 9 , Takuya Tomioka 10 , Hiroyuki Ozawa 5 and Kaoru Ogawa 5 1 Department of Otorhinolaryngology–Head and Neck Surgery, Kawasaki Municipal Kawasaki Hospital, Kawasaki, Kanagawa, Japan 2 Department of Otorhinolaryngology, Kyosai Tachikawa Hospital, Tachikawa, Tokyo, Japan 3 Department of Otorhinolaryngology, Matsumoto Dental University, Matsumoto, Nagano, Japan 4 Department of Otorhinolaryngology, Yokohama Municipal Citizen’s Hospital, Yokohama, Kanagawa, Japan 5 Department of Otorhinolaryngology–Head and Neck Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan 6 Department of Otolaryngology–Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan 7 Department of Otorhinolaryngology, International University of Health and Welfare Atami Hospital, Atami, Shizuoka, Japan 8 Department of Otorhinolaryngology, Saitama Red Cross Hospital, Saitama, Saitama, Japan 9 Department of Otorhinolaryngology, Kamio Memorial Hospital, Chiyoda, Tokyo, Japan 10 Department of Otorhinolaryngology, Ashikaga Red Cross Hospital, Ashikaga, Tochigi, Japan Correspondence to: Yorihisa Imanishi, email: yorihisa@ja2.so-net.ne.jp Keywords: febrile neutropenia; TPF; monocyte count; neutrophil count; head and neck squamous cell carcinoma Received: February 09, 2018 Accepted: March 07, 2018 Published: April 10, 2018 ABSTRACT Background: Febrile neutropenia (FN) is the most serious hematologic toxicity of systemic chemotherapy. However, accurate prediction of FN development has been difficult because the risk varies largely depending on the chemotherapy regimen and various individual factors. Methods: We retrospectively analyzed diverse clinical factors including pretreatment hematological parameters to clarify the reliable predictors of FN development during chemotherapy with a docetaxel, cisplatin, and fluorouracil (TPF) regimen in patients with head and neck squamous cell carcinoma. Results: Among the 50 patients, grade ≥3 neutropenia, grade 4 neutropenia, and FN developed in 36 (72%), 21 (42%), and 12 (24%) patients, respectively. Multivariate logistic regression revealed that a pretreatment absolute monocyte count (AMC)

Pyoderma gangrenosum is a rare ulcerative condition associated with various systemic diseases. Lesions on the lower extremities and the trunk are common, but lesions on the nose are rare. Here we report a case of pyoderma gangrenosum on the nose. A 33-year-old woman presented with fever, nasal obstruction, and painful swelling on the nasal bridge. Physical examination revealed swellings on the nasal septal mucosa bilaterally. Computed tomography showed a septal abscess and a subcutaneous abscess on the nasal bridge. The lesions worsened despite treatment with intravenous antibiotics and abscess drainage. Meanwhile, the patient also complained of bloody stools and was diagnosed with ulcerative colitis. Therefore, pyoderma gangrenosum on the nose was suspected, and was diagnosed by exclusion of other diseases. Treatment with systemic corticosteroids was started and the nasal lesions improved rapidly. However, saddle nose deformity occurred. A review of the literature reveals that pyoderma gangrenosum on the nose can cause ulcerations, septal abscess, and sinusitis. Further, there is a high likelihood of nasal complications, including saddle nose deformity, septal perforation, and skin defects. Pyoderma gangrenosum should be included in the differential diagnosis when nasal ulceration, abscesses, and sinusitis do not improve with antibiotics and drainage.

Due to the complex mechanisms involved in butanol-induced stress response, butanol tolerance phenotype is difficult to engineer even in microorganisms with well-defined genetic backgrounds. We therefore aimed to isolate butanol-tolerant microorganisms from environmental samples as potential alternative hosts for butanol production. Soil samples collected were subjected to butanol stress. A microbial strain capable of 2.5-3 % (w/v) butanol tolerance was isolated and identified as Enterococcus faecium by 16S rDNA analysis. The isolate grew readily under both aerobic and anaerobic conditions and was capable of producing butanol anaerobically. In comparison with the obligate anaerobe Clostridium acetobutylicum, the growth under both aerobic and anaerobic conditions of the isolated strain, together with no detection of butyrate and lack of two-phase fermentation suggests different metabolic networks from the obligate anaerobe C. acetobutylicum. Under anaerobic condition, butanol reached up to 0.4 gl(-1) in a batch culture without heterologous introduction of butanol biosynthetic pathway. Besides butanol tolerance, the isolated E. faecium IB1 showed high tolerance to 10 % (w/v) ethanol and 3 % (w/v) isobutanol. With distinct features including high butanol tolerance and natural butanol production, the isolated E. faecium IB1 with minimum metabolic engineering can be explored as a potential host for butanol production.

A solution-phase total synthesis of argifin using 3,4,5-tris(octadecyloxy)benzyl tag as a hydrophobic protective group of carboxylic acid was developed to produce 44% overall yield for 16 linear steps. Argifin, a novel class of natural product chitinase inhibitor, is a highly water-soluble cyclic pentapeptide, so hitherto, only solid-phase synthesis techniques have been used to conveniently prepare the compound and its derivatives. 3,4,5-Tris(octadecyloxy)benzyl alcohol (HO-TAGa) and its esters are highly crystalline materials and highly capable of dissolving in less-polar solvents such as dichloromethane, benzene, THF, etc., but insoluble in polar solvents such as methanol and DMSO. The combination of HO-TAGa and Fmoc-based peptide synthesis, together with simple purification by recrystallization from MeOH solution, furnished an efficient and practical route of argifin production in the liquid-phase.

In situ click chemistry is a target-guided synthesis technique for discovering potent protein ligands by assembling azides and alkynes into triazoles inside the affinity site of a target protein. We report the rapid discovery of a new and potent inhibitor of bacterial chitinases by the use of in situ click chemistry. We observed a target-templated formation of a potent triazole inhibitor of the chitinase-catalyzed chitin hydrolysis, through in situ click chemistry between a biologically active azide-containing scaffold and structurally unrelated alkyne fragments. Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides and antiasthmatics. Argifin, which has been isolated and characterized as a cyclopentapeptide natural product by our research group, shows strong inhibitory activity against chitinases. As a result of our efforts at developing a chitinase inhibitor from an azide-bearing argifin fragment and the application of the chitinase template and a library of alkynes, we rapidly obtained a very potent and new 1,5-disubstituted triazole inhibitor against Serratia marcescens chitinase (SmChi) B. The new inhibitor expressed 300-fold increase in the inhibitory activity against SmChiB compared with that of argifin. To the best of our knowledge, our finding of an enzyme-made 1,5-disubstituted triazole, using in situ click chemistry is the second example reported in the literature.

症例は68歳，男性．2006年12月の検診での上部消化管透視で胃に異常を指摘された．その後の内視鏡検査で胃体上部後壁にBorrmann3型腫瘍を認め胃癌（低分化腺癌）と診断された．腹部CTでは胃後壁に造影効果を伴った腫瘤，小彎側に複数の腫大リンパ節を認めた．膵臓に転移は確認できなかった．2007年1月に手術を施行，リンパ節はNo.1，3，4d，7，11pが腫大し一部膵への浸潤を認めた．さらに膵尾部に径15mmの孤立性腫瘤を触知した．S-T3，N2，H0，P0，CY0，M1（panc）StageIV，術式は胃全摘兼膵脾合併切除（D2郭清）とした．病理診断では胃原発巣は中分化型管状腺癌，壁深達度SS，N3（4sb，11p，11d，16a2計4/94），膵実質内の腫瘍も胃と同様の組織像を示す中分化型管状腺癌で胃壁，リンパ節との連続性はなく単発性の膵転移と診断した．術後14カ月，再発の徴候はなく外来通院中である．

In the 45 nm half pitch node, a mask induced polarization effect appears. Because of this effect, intensity of diffracted light depends on a pattern size and a diffraction order. This is pronounced in an attenuated phase shift mask (attPSM). A mask topography effect has to be considered for rigorous simulation. A small window attributable to diffraction efficiency is generated, because of an insufficient ratio of 1st order and 0th order diffracted light from the attPSM. Two approaches to produce a sufficient ratio, namely, a low transmittance layer attPSM and a biased pattern attPSM, were investigated by simulation. A mask bias of more than 10 nm on both sides is required to generate an optimal diffraction efficiency ratio for the 0th and 1st orders. The low transmittance (around 1%) attPSM had higher contrast at 45 nm half pitch in the resist image than the biased attPSM. It was also shown that a phase difference between diffraction orders caused lower contrast imaging.

症例は73歳,女性.食欲不振を主訴に近医を受診した.腹部超音波検査にて嚢胞性肝腫瘤を指摘され,当科を紹介された. 入院時,全身状態良好で体温36.3°C, 身体所見では手術痕以外には,異常所見を認めなかった. CT, MRIにて肝右葉前区域に,不均一に造影される,肥厚した嚢胞壁を伴い隔壁を有する多房性嚢胞性腫瘤を認めた.血管造影検査では腫瘍濃染像, encasement, 肝動脈門脈シャントを認めた.一方,下部消化管検査にて2型直腸癌を認めた. 以上より嚢胞性肝腫瘤の鑑別診断として肝嚢胞腺癌,転移性肝腫瘍,肝細胞癌などを含めた悪性の腫瘍を強く疑い,直腸低位前方切除術,肝前区域切除術を施行した.病理組織学的には嚢胞性肝腫瘤に悪性所見を認めず,細菌培養検査よりKlebsiella. pneumoniaeが検出され,肝膿瘍と診断した. 術前診断にて悪性を否定しえなかった肝膿瘍の1切除例を経験したので,若干の考察を加え報告する.

From results of ACTS-GC,postoperative adjuvant chemotherapy,administration of S-1 for one year has become the standard for gastric cancer of Stage II and III except T1. We inspected problems of adjuvant chemotherapy by S-1 by dose rate, an adverse event,and compliance. For the period from July 2006 to December 2008,among 41 cases of stage II/stage III gastric cancer, S-1 was as started as adjuvant therapy by for 28 cases (68.3%). Among 14 cases (63.6%) considered able to complete S-1 treatment for one year, 7 cases (31.8%) had to have their dose reduced or their administration schedule changed. No adverse event of grade 3/4 was found, but cancellation or reduced dose was necessary due to anorexia, malaise, diarrhea, severe skin reaction, and leukopenia resulting from myelosuppression. Thirteen patients took no S-1, and two (4.9%) of them took UFT, while 11 cases (26.8%) became a no-treatment follow-up group for reasons of age, coexisting symptoms and other reasons. The problem in the future is to improve compliance, and to establish a treatment strategy for patients who do not meet administration criteria and for patients for whom continuation of drug administration is impossible.

A vanillin-tolerant strain of Saccharomyces cerevisiae was screened and its intracellular ergosterol levels were compared with several laboratory yeast strains to study the potential relationship between ergosterol content and vanillin tolerance. Saccharomyces cerevisiae NBRC1950 was selected as a vanillin-tolerant strain. Its ergosterol content was higher than those of the laboratory strains. The results of DNA microarray and quantitative reverse transcriptase-polymerase chain reaction analysis showed that five genes involved in ergosterol biosynthesis (ERG28, HMG1, MCR1, ERG5, and ERG7) were upregulated in NBRC 1950 compared with strain X2180, suggesting that high expression of genes involved in ergosterol biosynthesis may cause high ergosterol content in strain NBRC 1950. The S. cerevisiae HX strain, which was a high-ergosterol-containing strain derived from X2180, was more tolerant to vanillin than the parental strain, suggesting that high ergosterol content may, in part, be responsible for vanillin tolerance. These findings provide a biotechnological basis for the molecular engineering of S. cerevisiae with increased tolerance to vanillin.

The purpose was to investigate side effects of FEC100 treatment, particularly bone marrow suppression, nausea and vomiting.We investigated side effects of FEC100 at the time of initial administration in 49 breast cancer patients (including 3 with recurrence). We used a 5-HT3 receptor antagonist as an antiemetic agent, steroids and Haloperidol, an antidopamine agent. Antibiotics were also administered for five days from day 10.The mean nadir of white blood cell count was 1,492+/-575 microL, and the mean day on which the nadir was reached was the 13.0+/-1.45th day. Leukopenia of less than 1,000 microL (grade 4) was seen in 8 (16.3%) of the 49 patients, and the incidence of leukopenia was particularly high (3/6, 50%) in patients with multiple bone metastases. Febrile neutropenia occurred in 4 (8.1%) of the 49 patients, 2 of those 4 patients having multiple bone metastasis. Fifteen (30.6%) of the 49 patients had nausea, and 3 patients (6.1%) had vomiting.The results indicate that side effects of FEC100 treatment are tolerable. However, care is needed for patients with multiple bone metastases because of the strong bone marrow suppression in such patients.

We investigated GroEL substrates from Bacillus subtilis 168 using the single-ring mutant of B. subtilis GroEL. We identified 28 candidates for GroEL substrates, of which Spo0B, Ald, Eno, SpoIIP, and FbaA were involved in spore formation, and Rnc, Tuf, Eno, Tsf, and FbaA were essential for B. subtilis growth. As observed at the protein level, the amount of SpoIIP interaction with GroEL increased at 3 h after initiation of sporulation.

We investigated a temperature adaptation of Bacillus subtilis 168 in which chromosomal groEL was replaced with a psychrophilic groEL. This strain can grow at 50 degrees C but not at 51 degrees C, a temperature at which wild-type B. subtilis can grow. Using in vivo random mutagenesis by the B. subtilis mutator strain (mutS, mutM, mutY), two thermo-adaptants were isolated from the groEL substituted strain at 52 degrees C. They contained novel amino acid alterations in their ATP binding motif (T93I) and the inter-monomer contact (R285H) region of GroEL. These results suggest that GroEL participates in bacterial temperature adaptation.

Aim Suramin is a symmetrical polysulfonated naphthylamine derivative of urea. There have been few studies on the effect of suramin on cytokines. We examined the effects of suramin on production of inflammatory cytokines. Methods We made an acute liver injury model treated with d -galactosamine (GalN) and lipopolysaccharide (LPS). Plasma AST, ALT, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were measured. We compared with survival rate, histological found and NF-κB activity between with and without treatment of suramin. In macrophage like cell line, TNF-α and IL-6 production, TNF-α and IL-6 mRNA expression, and NF-κB activity was measured. Results The lethality of mice administered suramin with GalN/LPS was significantly decreased compared with that in mice without suramin. Changes of hepatic necrosis and apoptosis were slight in suramin-treated mice. Serum AST, ALT, TNF-α, IL-6 levels and NF-κB activity in the liver were significantly lower in mice administered suramin. In an in vitro model, suramin preincubation inhibited TNF-α and IL-6 production, TNF-α and IL-6 mRNA expression, and NF-κB activity. Conclusions Suramin inhibits TNF-α and IL-6 production through the suppression of NF-κB activity from macrophages and shows therapeutic effects on acute liver damage.

In recent low-k1 lithography, the size of a mask pattern is becoming close to wavelength of the light source. The light intensity through the mask pattern is depending on polarization. TM polarization light is higher transmission than TE polarization light for a MoSi mask. This effect influences not only the zeroth-order light but the first-order light. On the other hand, TE polarization imaging makes higher contrast than TM polarization in two beam interference. Effects of polarization to resolution are not simple. Since an attenuated phase shift mask is used in order to obtain high contrast, it is necessary to take into consideration the influence of that. It is also taken into consideration that illumination light is not perpendicular incidence but oblique incidence for an ArF hyper-NA tool. We will perform a rigorous simulation in consideration of the above conditions. Hereby influence of the to the utmost resolution will be clarified by the rigorous simulation.

Genipin is a metabolite derived from the herbal medicine Inchinko-to. Little is known about the mechanism of genipin action on acute liver injury through inflammatory cytokines. We examined the effects of genipin on production of TNF-alpha in vivo and in vitro. Mice were given GalN/LPS with or without genipin treatment. All mice not given genipin died within 12h. But in mice given genipin, 8 of 15 mice survived for 24h after GalN/LPS administration. Histologically, hepatic necrosis and inflammatory cells infiltration were significantly slight in mice given genipin. Serum AST and ALT activity were significantly lower in mice given genipin. Serum and liver homogenate TNF-alpha levels were significantly lower in mice given genipin. However, in IL-6 and IL-1beta, there were no significant differences in mice given and not given genipin. TNF-alpha, NF-kappaB activation and TNF-alpha mRNA expression in a cultured mouse macrophage-like cell line J774.1 were significantly suppressed by genipin administration. In conclusion, the present findings suggest that genipin, a metabolite derived form the herbal medicine Inchinko-to improved acute liver dysfunction by suppressive effect of TNF-alpha production.

We have studied the lithography issue of resist footing in an ion implant layer after a gate conductor formation. In a previous report , we proposed the shadow model and showed a solution to reduce the resist footing. This paper reports on the further investigation into the cause and the reduction method of the resist footing over non-planar wafer with simulation and explains the effects with the shadow model. We analyzed the processes that affected the resist footing and four main effects were selected. These were NA, illumination coherency, mask bias, and mask type. We simulated these four effects on an orthogonal array by using the design of experiments (DOE). We obtained a better condition of higher NA, smaller coherency, positive mask bias, and Att-PSM for reducing the resist footing. We explain the reasons for these effective factors with the shadow model.

Standard simulations of optical projection systems for lithography with scalar or vector methods of Fourier optics make the assumption that the wafer stack consists of homogeneous layers. We introduce a general scheme for the rigorous electromagnetic field (EMF) simulation of lithographic exposures over non-planar wafers. Rigorous EMF simulations are performed with the finite-difference time-domain (FDTD) method. The described method is used to simulate several typical scenarios for lithographic exposures over non-planar wafers. This includes the exposure of resist lines over a poly-Si line on the wafer with orthogonal orientation, the simulation of “classical” notch problems, and the simulation of lithographic exposures over wafers with defects.

The authors investigated the types of additive nonreactive fluorinated surfactants that effectively decrease the release energy of a certain ultraviolet-cured base resin for radical photopolymerization. The release energies of resins containing various surfactants were compared in two atmospheres, namely air and 1,1,1,3,3-pentafluoropropane (PFP, HFC-245fa). Tridecafluoro-1,1,2,2-tetrahydrooctan-1-ol functioned as the most effective surfactant under an air atmosphere, for detachment of a silica surface modified with tridecafluoro-1,1,2,2-tetrahydrotrimethoxysilane from the cured resins. Under a PFP atmosphere, heptadecafluoro-1,1,2,2-tetrahydrodecan-1-ol with a longer fluoroalkyl chain was necessary to effectively decrease the release energy. It was indicated that the segregation of liquid fluoroalkyl alcohols between the cured resin and modified mold was effective in decreasing the release energy of cured resins.

In recent low-k1 lithography, the size of a mask pattern is becoming close to the wavelength of the light source. In a sub-100-nm pattern at wafer scale of 4× masks, transverse electric (TE) polarization light had higher transmittance of the zeroth order than TM polarization for a Cr mask according to rigorous model simulation of a finite difference time domain method. On the other hand, transverse magnetic (TM) polarization light had higher transmittance than TE polarization light for a MoSi mask. From the results of lithography simulation for a 45-nm pattern on the MoSi mask, TE polarization was better for wide exposure latitude, but TM polarization was better for large depth of field. The performance of a current MoSi mask is inferior to that of a Cr mask. However, a lower transmittance MoSi mask has better performance in the exposure defocus window under the dipole illumination. Also, rigorous simulation showed transmittance dependency of the light incident angle to the MoSi mask. The dependency was larger for TM polarization than for TE polarization.

We report a problem regarding DUV lithography on topographical substrates and a solution for obtaining desired CD control and resist pattern shape. In our experiment, large footings for a 250-nm resist pattern are observed when the resist pattern is transferred over a polysilicon step pattern of 175 nm in height. This pattern error is not negligible regarding device performance. The exposure tool used is a KrF scanner of NA 0.6. The resist is 500 nm thick with no antireflective coating (ARC). Computer simulation is used to demonstrate the amount of the footing. A nonrigorous diffraction model did not recreate the footing appearance at the poly-Si step. However, a rigorous diffraction model of incident light in a cone recreated the footing amount at the poly-Si step faithfully. In this simulation, optical distribution in the resist over the nonplanar wafer is solved by the finite-difference time-domain (FDTD) method. Optical intensity at the sidewalls of the step differs between the two models. Experimental results as well as simulation results show that larger coherency results in larger footing. In the case of a large coherency, the illumination rays come from various directions to the wafer, and a large shadow area is likely to appear behind the steep step. We also propose a shadow model for simple footing simulation. As a consequence, optical behavior in the vicinity at the steep step has a strong impact on the resist footing.

Phenotype frequencies and haplotype of HLA antigens in 297 cases with various bronchopulmonary diseases were studied using the method of lymphocyte microcytotoxicity test. The following results were obtained.1. High frequencies of HLA-A2, HLA-A9, HLA-B5, HLA-BW40 were recognized in normal individuals.2. HLA-BW21 in the patients with chronic bronchitis was higher than those in normal individuals (P

Background Lignocellulosic materials are abundant and among the most important potential sources for bioethanol production. Although the pretreatment of lignocellulose is necessary for efficient saccharification and fermentation, numerous by-products, including furan derivatives, weak acids, and phenolic compounds, are generated in the pretreatment step. Many of these components inhibit the growth and fermentation of yeast. In particular, vanillin is one of the most effective inhibitors in lignocellulose hydrolysates because it inhibits fermentation at very low concentrations. To identify the genes required for tolerance to vanillin, we screened a set of diploid yeast deletion mutants, which are powerful tools for clarifying the function of particular genes. Results Seventy-six deletion mutants were identified as vanillin-sensitive mutants. The numerous deleted genes in the vanillin-sensitive mutants were classified under the functional categories for 'chromatin remodeling' and 'vesicle transport', suggesting that these functions are important for vanillin tolerance. The cross-sensitivity of the vanillin-sensitive mutants to furan derivatives, weak acids, and phenolic compounds was also examined. Genes for ergosterol biosynthesis were required for tolerance to all inhibitory compounds tested, suggesting that ergosterol is a key component of tolerance to various inhibitors. Conclusion Our analysis predicts that vanillin tolerance in Saccharomyces cerevisiae is affected by various complicated processes that take place on both the molecular and the cellular level. In addition, the ergosterol biosynthetic process is important for achieving a tolerance to various inhibitors. Our findings provide a biotechnological basis for the molecular engineering as well as for screening of more robust yeast strains that may potentially be useful in bioethanol fermentation.