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We conducted a multicenter prospective study on whether a comprehensive geriatric assessment (CGA) can predict the adverse events (AEs) of chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients aged ≥ 65 years with newly diagnosed DLBCL underwent a pretreatment baseline CGA consisting of six assessment tools: activities of daily living (ADL), instrumental ADL (IADL), mood, nutritional status, comorbidities, and cognitive function. An attending physician chose each patient's treatment but was blind to CGA results. Patients were grouped as "dependent" or "independent" according to the CGA. The primary endpoint was to evaluate the association between chemotherapy-induced grade 3–4 toxicity and CGA. Of 86 patients, 78 completed the designated CGA. The median age was 79 years (65–89). Seventy-two patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP-like) regimen, and six were treated with low-toxicity regimens. Forty-one patients were classified as dependent and 37 as independent. In multivariate analysis, an impairment of IADL was independently associated with grade 3–4 leukopenia (odds ratio [OR] 0.63; 95% confidence interval [CI] 0.43–0.92, p = 0.017) and anemia (OR 0.67; 95% CI 0.50–0.90, p = 0.008). The presence of a comorbidity was also associated with grade 3–4 non-hematological toxicity (OR 2.17; 95% CI 1.37–3.43, p = 0.001). The 4-year survival rate tended to be longer in the independent (72.7%) compared to dependent (56.9%) group. Overall, a CGA may be a useful tool for predicting serious AEs associated with chemotherapy in elderly patients with DLBCL. [ABSTRACT FROM AUTHOR]

Combined oral cyclophosphamide and capecitabine (XC) chemotherapy is used for metastatic breast cancer (MBC) patients. We report herein two MBC patients who developed severe hemorrhagic cystitis after XC therapy. Case 1: A 67-year-old woman with MBC had received XC therapy for 2.5 years. After a sudden onset of lower abdominal pain and gross hematuria, cystoscopy revealed a urinary bladder mucosa showing diffuse dilation of the capillaries and a large blood clot. A total dose of 60.8 g cyclophosphamide had been given and the XC regimen was discontinued immediately. The patient experienced frequent episodes of bladder tamponade over 18 months and underwent continuous bladder irrigation and cystoscopic fulguration. Hyperbaric oxygen therapy (HBOT) provided only temporary relief and the patient subsequently developed hemorrhagic shock. A bilateral ureterostomy was eventually performed. Case 2: A 65-year-old woman with MBC was given XC for 3 years, but this was discontinued after she developed new lung lesions. The patient was given a total dose of 78.4 g of cyclophosphamide. A month later, the patient complained of intermittent gross hematuria, which progressed to persistent macroscopic hematuria for 1 week. She underwent continuous bladder irrigation with saline, without an improvement in her bladder tamponade. Subsequently, the bleeding ceased completely after HBOT. Some MBC cases can be controlled for a long time with XC therapy. For those cases, we need to realize that severe hemorrhagic cystitis may occur. Even at a low dose, requires testing periodically for occult blood in the urine to detect the early stages of cystitis. [ABSTRACT FROM AUTHOR]

The rotational spectrum of one conformer of the methyl glycolate–H 2 O complex has been measured by means of the pulsed jet Fourier transform microwave spectrometer. The observed a - and b -type transitions exhibit doublet splittings due to the internal rotation of the methyl group. On the other hand, most of the c -type transitions exhibit quartet splittings arising from the methyl internal rotation and the inversion motion between two equivalent conformations. The spectrum was analyzed using parameterized expressions of the Hamiltonian matrix elements derived by applying the tunneling matrix formalism. Based on the results obtained from ab initio calculation, the observed complex of methyl glycolate–H 2 O was assigned to the most stable conformer of the insertion complex, in which a non-planer seven membered-ring structure is formed by the intermolecular hydrogen bonds between methyl glycolate and H 2 O subunits. The inversion motion observed in the c -type transitions is therefore a kind of ring-inversion motion between two equivalent conformations. Conformational flexibility, which corresponds to the ring-inversion between two equivalent conformations and to the isomerization between two possible conformers of the insertion complex, was investigated with the help of the ab initio calculation. [ABSTRACT FROM AUTHOR]

We describe a new measurement method for liquid–liquid interfacial tension via a floating droplet profile (floating drop method), on a liquid. The accuracy of the floating drop method was confirmed for an oil-aqueous solution system. Specifically, we measured the interfacial tension between a floating rapeseed oil droplet and a 0.2% aqueous solution of polyoxyethylene alkyl ether sulfuric acid ester salt. In addition, it was confirmed that the tensile balance at the edge of the oil droplet floating on the aqueous solution, which is known as Neumann’s triangle, is satisfied in the present system. [ABSTRACT FROM AUTHOR]

Background Evidence of eribulin therapy for metastatic breast cancer ( MBC) in clinical practice is not well documented. Methods We retrospectively analyzed the safety and efficacy of eribulin in 29 MBC patients from 2011 to 2016 at Fukuoka University Hospital. Results The median patient age, number of courses, total dose, and relative dose intensity were as follows: 65 years, five courses, 8.6 mg/m2, and 75%, respectively. One patient achieved a complete response, ( CR) six a partial response ( PR), eight stable disease ( SD) and 14 patients exhibited progressive disease. The objective response rate ( ORR: CR + PR) was 24.1%, and the clinical benefit rate ( CBR: CR + PR + SD) was 51.7%. The median progression-free survival was 90 days (95% confidence interval [ CI] 67-126) and median overall survival was 264 days (95% CI 198-357). In patients who previously received 2-4 regimens, the ORR was 28.5% and the CBR was 57.1%. In patients who received 5-12 regimens, the ORR was 20% and the CBR was 45%. Chemotherapy was administered to 20 patients (69%) after eribulin administration, and the median overall survival rate of cases that achieved greater than a PR was 1088 days. The most frequent treatment-related grade 3/4 adverse events were neutropenia (55.2%), and febrile neutropenia (20.1%). Grade 3 peripheral neuropathy occurred in 13.8% of patients, but was not exacerbated even if present before treatment. Conclusion Eribulin is effective for MBC patients who have received multiple chemotherapies. Neutropenia and febrile neutropenia may develop after heavy prior therapy. [ABSTRACT FROM AUTHOR]

As tongue cancer is one of the major malignant cancers in the world, understanding the mechanism of maintenance of lingual epithelial tissue, which is known to be the origin of tongue cancer, is unquestionably important. However, the actual stem cells that are responsible for the long-term maintenance of the lingual epithelium have not been identified. Moreover, a simple and convenient culture method for lingual epithelial stem cells has not yet been established. Recently, we have shown that Bmi1-positive cells, residing at the second or third layer of the epithelial cell layer at the base of the interpapillary pit (IPP), were slow-cycling and could supply keratinized epithelial cells for over one year, indicating that Bmi1-positive cells are long-term lingual epithelial stem cells. In addition, we have developed a novel lingual epithelium organoid culture system using a three-dimensional matrix and growth factors. Here, we discuss current progress in the identification of lingual stem cells and future applications of the lingual culture system for studying the regulatory mechanisms of the lingual epithelium and for regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia, and it causes a high rate of complications such as stroke. It is known that AF begins as paroxysmal form and gradually progresses to persistent form, and sometimes it is difficult to identify paroxysmal AF (PAF) before having stroke. The aim of this study is to evaluate the risk of PAF and stroke using genetic analysis and circulating biomarkers. Materials and methods: A total of 600 adult subjects were enrolled (300 from PAF and control groups). Peripheral blood was drawn to identify the genetic variation and biomarkers. Ten single nucleotide polymorphisms (SNPs) were analyzed, and circulating cell-free DNA (cfDNA) was measured from plasma. Four microRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were quantified in serum using quantitative RT-PCR. Results: Genotyping identified 4 single nucleotide polymorphisms (SNPs) that were significantly associated with AF (rs6817105, rs3807989, rs10824026, and rs2106261), and the genetic risk score using 4 SNPs showed the area under the curve (AUC) of 0.631. Circulating miRNAs and cfDNA did not show significant differences between PAF and control groups. The concentration of cfDNA was significantly higher in patients with a history of stroke, and the AUC was 0.950 to estimate the association with stroke. Conclusion: The risk of AF could be assessed by genetic risk score. Furthermore, the risk of stroke might be evaluated by plasma cfDNA level. [ABSTRACT FROM AUTHOR]

Abstract: The influence of quinone structures related to the formation of the “colloidal deposit” on Pb electrode immersed into water containing lignin preparations or pure organic compounds has been investigated. It was found that quinone structures in lignin preparations, as well as in pure organic compounds, play an important role in the formation of the “colloidal deposit”. [Copyright &y& Elsevier]

Myocardial infarction (MI) is one of the common diseases whose pathogenesis includes genetic factors. To reveal genetic backgrounds of this clinically heterogeneous disorder, we started our case-control association study by examining large-scale gene-based single nucleotide polymorphism (SNP) sets for ∼1,000 patients and controls. As a core genotyping method, a combination of multiplex PCR and Invader method was used, and after genotyping ∼65,000 SNPs, we found two SNPs located within lymphotoxin-α ( LTA) gene showing significant association with MI. LTA is one of the cytokines produced in the early stages of vascular inflammatory processes. These SNPs seem to be involved in inflammation by both qualitatively and quantitatively modifying the function of LTA protein, thereby conferring a risk of MI. The genetic association was further confirmed by other researchers using white European trios. To further understand the roles of LTA protein in the pathogenesis of MI, we searched for proteins that interact directly with LTA protein and identified galectin-2 protein as a binding partner of LTA protein. It is a member of galactose-binding lectin family whose function has not been well characterized. Genetic association study again revealed that an SNP in LGALS2 encoding galectin-2 was also associated with susceptibility to MI. This genetic substitution seemed to affect the transcriptional level of galectin-2, which led to altered secretion of LTA, thereby affecting the degree of inflammation. Thus, our findings indicate the importance of inflammation, especially the LTA cascade, in the pathogenesis of MI. Also, combined strategy of genetic and molecular-cellular biological approaches may be useful for clarification of the pathogenesis of common diseases in general. [ABSTRACT FROM AUTHOR]

Gene targeting using short interfering RNA (siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. For the application of siRNA technology to gene therapy, however, still more efficient transduction of siRNA into target cells is needed. In this study, we developed an adenoviral vector harboring a tandem-type siRNA expression unit, in which sense and antisense strands composing the siRNA duplex were separately transcribed by two human U6 promoters. Targeting survivin, an antiapoptotic molecule widely overexpressed in malignancies but not detected in terminally differentiated adult tissues, this type of adenoviral vector (Adv-siSurv) successfully exerted a gene knockdown effect and induced apoptosis in HeLa, U251, and MCF-7 cells. These cancer cells, once infected with Adv-siSurv, displayed remarkably attenuated growth potential, both in vitro and in vivo. Moreover, intratumoral injection of Adv-siSurv significantly suppressed tumor growth in a xenograft model using U251 glioma cells. This novel modality may be a promising tool for cancer therapy. [Copyright &y& Elsevier]

Gallbladder cancer cells are stimulated by hepatocyte growth factor (HGF) in vitro and in vivo. We constructed an adenovirus vector, AdCMV.NK4, carrying the HGF antagonist HGF/NK4 (NK4) and evaluated whether or not this vector can suppress the peritoneal implantation of gallbladder cancer in a novel peritoneal injury mouse model. A human gallbladder cancer cell line (GB- d1) and human peritoneal mesothelial cells infected with the adenovirus vector produced a substantial level of NK4 protein. An invasion of GB-d1 cells was determined by a coculture with AdCMV.NK4-infected human mesothelial cells in vitro. Both the invasion and migration of GB-d1 cells were dramatically inhibited by this vector in a multiplicity of infection (MOI)-dependent manner. GB-d1 cells were intraperitoneally injected into the nude mice with peritoneal injury, followed by either AdCMV.NK4 or a control vector (AdCMV.LacZ). The incidence and the size of the metastatic tumor drastically decreased by AdCMV.NK4 (MOI 100: n = 4, P<.0001). Real-time PCR analysis revealed a transient elevation of mouse HGF mRNA expression at the peritoneal injury sites. AdCMV.NK4 has been suggested to induce the inhibition of the implantation and growth of gallbladder cancer cells in vivo through its anti-HGF activity, and the use of NK4 gene transfer could be an effective modality for preventing peritoneal metastasis of gallbladder cancer. [ABSTRACT FROM AUTHOR]

The epidermis of higher plants generates the cuticle layer that covers the outer surface of each plant. The cuticle plays a crucial role in plant development, and some mutants with defective cuticle exhibit morphological abnormalities, such as the fusion of organs. The way in which the cuticle forms and its contribution to morphogenesis are poorly understood. Conventional detection of the cuticle by transmission electron microscopy (TEM) requires laborious procedures, which include fixation, staining with osmium, and preparation of ultra-thin sections. It is also difficult to survey entire surfaces of expanded leaves because of the limited size of specimens that can be examined. Thus, TEM is unsuitable for large-scale screening for mutants with defective cuticle. We describe here a rapid and inexpensive method, designated the toluidine-blue (TB) test, for detection of cuticular defects in whole leaves. We demonstrated the validity of the TB test using mutants of Arabidopsis thaliana, including abnormal leaf shape1 ( ale1), fiddlehead ( fdh), and five e cer iferum ( cer) mutants, in which the structure and/or function of the cuticle is abnormal. Genetic screening for mutants using the TB test allowed us to identify seven loci. The cuticle-defective regions of leaves of the mutants revealed five intrinsic patterns of surface defects (classes I through V), suggesting that formation of functional cuticle on leaves involves various spatially regulated factors. [ABSTRACT FROM AUTHOR]

Ossification of the posterior longitudinal ligament (OPLL) of the spine is a subset of 'bone-forming' diseases, characterized by ectopic ossification in the spinal ligaments. OPLL is a common disorder among elderly populations in eastern Asia and is the leading cause of spinal myelopathy in Japan. We performed a genomewide linkage study with 142 affected sib pairs, to identify genetic loci related to OPLL. In multipoint linkage analysis using GENE- HUNTER-PLUS, evidence of linkage to OPLL was detected on chromosomes 1p, 6p, 11q, 14q, 16q, and 21q. The best evidence of linkage was detected near D21S1903 on chromosome 21q22.3 (maximum Z[SUBlr] = 3.97); therefore, the linkage region was extensively investigated for linkage disequilibrium with single-nucleotidepolymorphisms (SNPs) covering 20 Mb. One hundred fifty positional candidate genes lie in the region, and 600 gene-based SNPs were genotyped. There were positive allelic associations with seven genes (P < .01 ) in 280 patients and 210 controls, and four of the seven genes were clustered within a region of 750 kb, ∼1.2 Mb telomeric to D21S1903. Extensive linkage disequilibrium and association studies of the four genes indicated that SNPs in the collagen 6A1 gene (COL6A1) were strongly associated with OPLL (P = .000003 for the SNP in intron 32 [-29]). Haplotype analysis with three SNPs in COL6A1 gave a single-point P value of .0000007. Identification of the locus of susceptibility to OPLL by genomewide linkage and linkage disequilibrium studies permits us to investigate the pathogenesis of the disease, which may lead to the development of novel therapeutic tools. [ABSTRACT FROM AUTHOR]

The extent and distribution of linkage disequilibrium (LD) in humans is a current topic especially for gene mapping of complex diseases. Akaike's information criterion (AIC) was applied to estimate LD and compared with other standard LD measures, D' and r². By comparison of an independent model (IM; linkage equilibrium) and a dependent model (DM; linkage disequilibrium), the parsimonious model is the one with the smaller AIC score. Therefore, the extent of LD by AIC is expressed as AIC(IM) — AIC(DM)(AIC(LD)). A total of 39 singlenucleotide polymorphisms on a 1.6-Mb region of chromosome 21q22 were identified, and genotyped in 192 Japanese individuals. All possible pairs were analyzed to estimate LD and the analyses were compared. AIC(LD) became highly positive as the D' value increased and was negative at D' values of around 0.2. Because a negative value of AIC(LD) implies linkage equilibrium, D' values below 0.2 should be regarded as linkage equilibrium. The LD estimate by AIC yielded results similar to those obtained by r², indicating that AIC(LD) would be useful for fine gene mapping. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the role of genetic variants of interleukin-3 (IL-3) in the pathophysiology of rheumatoid arthritis (RA) in Japan. Association between RA and a single-nucleotide polymorphism in the IL-3 promoter region; Methodology; Results and discussion.

Abstract Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of drugs such as azathiopurine, 6-mercaptopurine, and 6-thioguanine, which are widely prescribed for immunosuppressive or cytotoxic applications. We report here the entire genomic structure of the TPMT gene and the presence of 30 single-nucleotide polymorphisms (SNPs) within that structure. The gene spans a genomic region about 27kb long and consists of nine exons. By screening its entire genomic sequence for SNPs in 48 Japanese chromosomes by direct DNA sequencing, we detected 1 SNP in the 870-bp promoter region, 26 SNPs in introns, and 3 SNPs in the 3' untranslated region (3'UTR) for investigating correlations between TPMT genotypes and the side-effects caused by thiopurine drugs. [ABSTRACT FROM AUTHOR]

Simple Summary: The accumulation of Lipiodol (ethiodized oil) after transarterial embolization is known to reflect tumor necrosis. In general, the treatment effect is evaluated by computed tomography; there has been no development in imaging modalities for several decades. A new technique, ultrasonic heating, can differentiate biological tissues based on the fact that tissues' characteristic sound velocity varies depending on the temperature. This technique could have the potential to evaluate treatment effect after transarterial embolization as an alternative to computed tomography. Computed tomography (CT) is the standard method to evaluate Lipiodol deposition after transarterial embolization (TAE) for a long period. However, iodine but not Lipiodol can be observed on CT. A minimally invasive other method to detect Lipiodol has been needed to evaluate accurate evaluation after procedure. The purpose of this study was to evaluate the efficacy of using the rate of change in sound velocity caused by ultrasonic heating to reflect Lipiodol accumulation after TAE in a rat liver tumor model. We analyzed the association of this developed technique with CT images and histological findings. Eight rats bearing N1S1 cells were prepared. After confirmation of tumor development in a rat liver, Lipiodol was injected via the hepatic artery. Seven days after TAE, CT scan and sound velocity changes caused by ultrasonic heating were measured, and then the rats were sacrificed. An ultrasonic pulse-echo method was used to measure the sound velocity. The temperature coefficient of the sound velocity in each treated tumor was evaluated and compared with the mean CT value and the histological Lipiodol accumulation ratio. Pearson's correlation coefficients were calculated to assess the correlation between the measured values. The correlation coefficient (r) of the mean CT value and histological Lipiodol accumulation ratio was 0.835 (p = 0.010), which was considered statistically significant. Also, those of the temperature coefficient of the sound velocity and the histological Lipiodol accumulation ratio were statistically significant (r = 0.804; p = 0.016). To our knowledge, this is the first study that reported the efficacy of ultrasonic heating to detect Lipiodol accumulation in rat liver tumors after TAE. Our results suggest that the rate of change in sound velocity caused by ultrasonic heating can be used to evaluate Lipiodol accumulation in liver tumors after TAE, and thus could represent an alternative to CT in this application. This new innovative technique is easy to treat and less invasive in terms of avoiding radiation compared with CT. [ABSTRACT FROM AUTHOR]

Cadherin molecules are essential for tissue morphogenesis and are also related to cancer invasion and metastasis. Although normal melanocytes express E- and P-cadherin, the activity and expression of E- and P-cadherin in melanoma cells are still unknown. We measured the homophilic adhesion activity of human normal epidermal melanocytes and the melanoma cell lines MeWo and A375. The melanoma cells showed stronger homophilic adhesion activity than did the melanocytes, despite the lower expression of E- and P-cadherin in the melanoma cells. This result suggested that melanoma cells expressed other types of homophilic adhesion molecules. Using degenerate primers to amplify multiple cadherin subtypes, we performed a polymerase chain reaction (PCR) with the first strand of cDNAs generated by reverse transcription of the mRNAs of the melanoma cells, and we isolated two known cadherin fragments, N-cadherin and PC42, and six novel cadherin fragments, cadherins ME1-ME6. The reverse transcriptase-PCR. using specific primers of cadherins including E-, P-, and N-cadherins, PC42, and cadherins ME1-M.E6 revealed that the melanoma cells expressed more kinds of cadherin molecules than did the melanocytes. Such cadherins may play an important role in melanoma cell-cell adhesion. [ABSTRACT FROM AUTHOR]

Epidermolysis bullosa acquisita is a subepidermal blistering disease in which patients have autoantibodies against the non-collagenous domain of type VII collagen. Starting with previously isolated 1-kilobase pair (Kb) cDNA for this au- toantigen, we isolated overlapping cDNAs with a combined open reading frame of -&SIM;3.2 Kb, encoding most (&SIM;115 kilo- daltons [KDa]) of the N-terminal non-collagenous domain of type VII collagen. To localize immunogenic domains, we produced maltose-binding fusion proteins with cDNA encoding different portions of this autoantigen. These cDNA fragments scan from 5' to 3' of this non-collagenous domain and overlap each other. An immunoblot analysis of these fusion proteins with eight epidermolysis bullosa acquisita patient sera demonstrated that each patient serum binds to different regions of this molecule and that epitopes for these patient sera locate throughout this autoantigen. These data suggest that multiple epitopes on the N-terminal non-collagenous domain of type VII collagen are recognized by circulating autoantibodies in patients with epidermolysis bullosa acquisita. [ABSTRACT FROM AUTHOR]

The various clinical features of adult T-cell leukemia/lymphoma (ATL) are frequently accompanied by skin eruptions. Recently, a cutaneous type of ATL has been proposed by clinical studies. We analyzed the viral integration of human T-cell leukemia virus-I (HTLV-I) and monoclonal rearrangement of T-cell receptor (TCR) gene in blood lymphocytes and the cutaneous infiltrated cells of nine ATL patients with various clinical features and skin eruptions. We classified them by the results of Southern blot analysis and propose a cutaneous-type ATL accordingly. In two of them, we could detect the monoclonal integration of HTLV-I and T-cell monoclonality only in the skin but not in the peripheral lymphocytes. We also demonstrated the time course study in one patient. Clinicians should be aware of the HTLV-I positive cutaneous T cell lymphoma that can be named cutaneous-type ATL. Examination of viral integration and T-cell monoclonality in skin lesions is required to make an exact diagnosis of cutaneous ATL. [ABSTRACT FROM AUTHOR]

A partial cDNA clone (called BP cDNA) with coding sequences for the carboxy-terminal region of bullous pemphigoid (BP) antigen has been recently isolated and sequenced. In order to determine whether specific peptides encoded by the cDNA could be used to raise antibodies against BP antigen, fusion proteins derived from fragments of the BP cDNA and 17-mer or 19-mer synthetic peptides, corresponding to its deduced amino acid sequence, were used to generate rabbit antibodies. Three restriction enzyme fragments, 1179 bp (5' end), 264 bp (middle), and 546 bp (3' end), of the 1992 open reading frame (ORF) of BP cDNA were subcloned in frame into pEX plasmids to make β-galactosidase fusion proteins FP1, FP2, and FP3, respectively. Fusion proteins of the predicted molecular weight, and which bound anti-β-galactosidase antibodies, were produced, confirming the length of the predicted ORF. Rabbits immunized with FP1, but not FP3, produced antibodies, similar to authentic antibodies from BP patients, which: 1) bound the epidermal basement membrane at titers over 10,000, as determined by indirect immunofluorescence; 2) bound the basement membrane on the roof of 1 M NaCl-split skin; 3) immunoprecipitated the 230-kD BP antigen; and 4) bound the hemidesmosome, as determined by immunoelectron microscopy. Rabbits immunized with FP2 also produced lower titer BP-like antibodies. We further showed that short hydrophilic synthetic peptides, contained in FP1, could induce similar BP-like antibodies in rabbits at immunofluorescence titers up to 2560. These rabbit antibodies should prove useful for further studies on the function and structure of particular epitopes of BP antigen as well as on the pathophysiology of disease. [ABSTRACT FROM AUTHOR]

T-cell populations of 22 plaque lesions from seven mycosis fungoides patients were studied for clonal rearrangement of the β chain of the T-cell receptor (Tβ gene. All plaque lesions employed in this study showed clinically similar appearance. Histologically, all the biopsy specimens showed epidermotropism and the dermal infiltration of mononuclear cells including atypical cells. Histochemically, the majority of the infiltrated cells had surface markers of helper T cells. DNA extracted from skin lesions, peripheral lymphocytes, and lymph nodes revealed that the monoclonal expansion of T cells was different among patients and lesions. DNA extracted from the two skin lesions of case 1 revealed a clonal expansion of T cells. The rearranged bands persisted for about 1 year. In contrast, all lesions from casts 3-7 showed no rearranged band. Interestingly, three lesions from case 2 showed mixed type results, i.e., the monoclonal expansion of T cells was detected in one lesion but not in the other two lesions. Time course study of case 2 revealed that the same rearranged hand became detectable in all three skin lesions and a lymph node about 1 year later. These results suggest that in plaque lesions of mycosis fungoides, there are various stages of detectable monoclonality of infiltrating cells, although the clinical appearance of the plaques was similar, and that the variety of monoclonality may reflect the long clinical course of this disease. [ABSTRACT FROM AUTHOR]

We constructed a high-density map of single-nucleotide polymorphisms (SNPs) present within a 31-kb region of human chromosome 13q31 that contains the human counterpart of the rabbit ITR gene, which encodes a rhodopsin-like G protein-coupled receptor associated with vascular remodeling. The elements of human ITR cDNA were distributed in 27,452 bp of genomic DNA; the nine exons ranged in size from 50 bp to 2271 bp, with an average size of 392 bp. We isolated a total of 22 SNPs from the ITR locus by systematically screening genomic DNA from 48 healthy Japanese individuals; three SNPs were present in the 5′ flanking region, two in coding elements, 12 in introns, and five in the 3′ untranslated region. By comparing our data with SNPs deposited in the dbSNP database in the National Center for Biotechnology Information, 19 of the 22 SNPs (86) were considered to be novel. The map presented here should help in evaluating the role of human ITR in cardiovascular diseases, in other diseases mapped to this segment on chromosome 13q31, and in a variety of pharmacogenetic effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, favorable outcomes have been reported for hepatocellular carcinoma treated with transarterial chemoembolization (TACE) combined with lenvatinib (LEN-TACE). However, the optimal treatment protocol remains unclear. In this study, we performed a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE). The objective was to assess changes in tumor hemodynamics following the 4-day lenvatinib administration and to evaluate the outcomes of this combined therapy. A significant decrease in intra-tumor flow after lenvatinib was observed, with a 100% technical success rate and no severe adverse events. Complete response rates (CR) at 1 month were 75%, and the 12-month progression-free survival (PFS) rate was 75.0%. The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction radio by lenvatinib prior to TACE (r = −0.55). The short-term LEN-TACE is feasible and safe, demonstrating promising results, including a high CR rate and prolonged PFS. Aim: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. Methods: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4–12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. Results: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = −0.55). The 12-month progression-free survival (PFS) rate was 75.0%. Conclusions: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory. [ABSTRACT FROM AUTHOR]

The effects of substance P and substance K, which are coexpressed in the same mRNA as a β-preprotachykinin in peripheral tissues and released in the inflammatory lesion of the skin, were examined on epidermal proliferation using spontaneously transformed mouse epidermal cell line (Pam 212 cells). Substance P stimulated the synthesis of DNA of Pam 212 cells in the medium containing 2%- 10% fetal calf serum (FCS). Stimulation of DNA synthesis was dose dependent if the cells were cultured in the medium containing 2% FCS (quiescent condition). This effect was inhibited by spantide. In a serum-free medium, substance P had no effect on keratinocyte proliferation. In contrast, substance K, which shares a common amino acid sequence with substance P on its C-terminal, did not affect DNA synthesis of Pam 212 cells in either medium condition. Substance P released in inflammation may stimulate epidermal proliferation. [ABSTRACT FROM AUTHOR]

Background: Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited. The aim of this study was to prospectively evaluate the feasibility, tolerability, and pharmacokinetics of selective transarterial chemoembolization (TACE) with irinotecan-loaded 40 μm microspheres combined with systemic FOLFIRI for colorectal liver metastases refractory to oxaliplatin regimen.Methods: The dose escalation study was conducted in three patient groups with different amounts of irinotecan loaded (50, 75 and 100 mg per mL-microspheres). Selective catheterization was performed to embolize subsegments or segments of located tumors using TACE navigation system. FOLFIRI was administrated 7 days after TACE. Plasma concentration was measured before and time points after administration.Results: Nine patients successfully underwent a total of 22 TACE procedures. Dose-limiting toxicity did not appear at any level. The overall response rate was 55.6%. The median progression free and overall survival were 8.1 and 18.2 months, respectively. The AUC and Cmax of plasma SN-38 per 1 mg injected irinotecan dose were significantly higher in irinotecan-loaded microspheres compared with FOLFIRI (P = 0.009 and P <  0.001, respectively).Conclusion: Selective TACE using 40 μm irinotecan-loaded microspheres combined with systemic FOLFIRI was feasible and safe even when a high dose of irinotecan was loaded. Irinotecan-loaded microspheres resulted in a higher plasma concentration and AUC of SN-38 than treatment with FOLFIRI. Further large scale trials to evaluate the efficacy are mandatory.Trial Registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367 ; Registered date; 08,10,2014. [ABSTRACT FROM AUTHOR]

Primary hepatic lymphoma (PHL) is a rare form of non-Hodgkin lymphoma primarily affecting the liver. We present a case of an 84-year-old man diagnosed with PHL, incidentally detected during abdominal ultrasonography. The ultrasonography showed a hypoechoic nodule. When examined by CEUS, the nodule showed hyperenhancement in the arterial phase and hypoenhancement in the portal and late phases. Conversely, CECT demonstrated hypoenhancement through all the phases. The patient declined a tumor biopsy and opted for follow-up care. Ten months later, the lobular mass had increased from 15 mm to 65 mm, presenting as hypoechogenic and demonstrating the "vessel-penetrating sign" on color Doppler imaging. CEUS revealed reticulated enhancement, indicating intratumoral vessels. The mass displayed hypoattenuation on plain CT, hypointensity in T1-weighted images, and hyperintensity in T2-weighted images and exhibited significant restriction in diffusion-weighted images. Both CECT and contrast-enhanced MRI exhibited hypoenhancement. The patient underwent a partial hepatic segmentectomy, and the mass was pathologically diagnosed as a diffuse large B-cell lymphoma. Subsequent postoperative radiological examinations revealed no other lesions, confirming the diagnosis of PHL. Our report highlights specific ultrasonographic signs of PHL observed from an early stage and presents a review of the relevant literature. [ABSTRACT FROM AUTHOR]

Background: The physical and biochemical factors responsible for cervical disc degeneration, and resulting in various spinal disorders, remain unclear. This study aimed to evaluate the correlation between cervical spinal canal stenosis and degeneration of intervertebral discs, and to analyze the factors related to disc degeneration in the Japanese population.Methods: Three hundred and forty-four Japanese general residents underwent investigations, including magnetic resonance imaging of the cervical spine, in our health check project. We measured anteroposterior diameters at the levels of the cervical spinal disc in mid sagittal plane magnetic resonance imaging and evaluated disc degeneration. Spearman correlation coefficient was used to evaluate whether the diameters were correlated with disc degenerative scores. Stepwise multiple linear regression analysis was conducted with the score of disc degeneration as the dependent variable; and age, physical measurement values, bone mineral density of the forearm, and the value of serum bone metabolic markers and amino acids as the independent variables for each sex.Results: As the age increased, the anteroposterior diameters decreased in both sexes. The minimum anteroposterior diameters were correlated with the disc degenerative scores (Spearman r = - 0.59, p < 0.001 in men, Spearman r = - 0.53, p < 0.001 in women). In multiple linear regression analysis, age, cross-linked N-telopeptide of type 1 collagen and isoleucine were significantly correlated with the cervical disc degenerative score in men (R2 = 0.47), and age and lysine were significantly correlated with the degenerative score in women (R2 = 0.50).Conclusion: The factors responsible for cervical disc degeneration differed between men and women. Whether modifying these significant factors is possible, or whether this intervention would contribute to prevention of disc degeneration requires future studies. [ABSTRACT FROM AUTHOR]

We recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells (LESCs), which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. However, the precise role of LESCs in generating tongue tumors and Bmi1-positive cell lineage dynamics in tongue cancers are unclear. Here, using a mouse model of chemically (4-nitroquinoline-1-oxide: 4-NQO) induced tongue cancer and the multicolor lineage tracing method, we found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. Although many Bmi1-positive cells within the tongue cancer specimens failed to proliferate, some proliferated continuously and supplied tumor cells to the surrounding area. This process eventually led to the formation of areas derived from single cells after 1-3 months, as determined using the multicolor lineage tracing method, indicating that such cells could serve as cancer stem cells. These results indicate that LESCs could serve as the origin for tongue cancer and that cancer stem cells are present in tongue tumors. [ABSTRACT FROM AUTHOR]

Background: The recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. Materials and Methods: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). Results: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10). Conclusion: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC. [ABSTRACT FROM AUTHOR]

Background: Studies have reported associations between neck pain and degenerative changes in the cervical spine in women, and between neck pain and obesity or metabolic syndrome. The present study investigated associations between neck pain or stiffness and lipid profiles in subjects recruited from the general population of a Japanese community.Methods: The 1122 volunteers who participated in this study included 426 men (age 52.6 ± 15.5 years; body mass index 23.6 ± 3.2) and 696 women (age 55.3 ± 15.3 years; body mass index 22.2 ± 3.4). Each subject filled out a questionnaire about any neck pain or neck-shoulder stiffness experienced in the previous 3 months. We recorded the following laboratory results related to metabolic factors, including lipid profiles: total cholesterol, LDL and HDL cholesterol, triglycerides, free fatty acids, glucose, and hemoglobin A1c. We conducted logistic and linear regression analyses using the prevalence of neck pain or neck-shoulder stiffness as the dependent variable and age, sex, body mass index, and laboratory data as independent variables.Results: There was no significant difference in the prevalence of neck pain between men (20.5%) and women (21.5%). However, the prevalence of neck and shoulder stiffness was significantly higher in women (60.3%) than in men (38.0%; P < 0.05). Logistic and linear regression analyses showed a significant negative correlation between the prevalence of neck pain and LDL cholesterol (odds ratio [OR], 0.958; 95% CI, 0.921-0.997), and between the prevalence of neck-shoulder stiffness and age (OR, 1.025; 95% CI, 1.013-1.038) and gender (OR, 0.362; 95% CI, 0.25-0.494).Conclusion: LDL cholesterol was correlated with neck pain in this cross-sectional population-based study. [ABSTRACT FROM AUTHOR]

We describe the clinical effects of short-term lenvatinib administration prior to conventional transarterial chemoembolization (cTACE) on tumor vasculature. Two patients with unresectable hepatocellular carcinoma underwent high-resolution digital subtraction angiography (DSA) and perfusion four-dimensional computed tomography during hepatic arteriography (4D-CTHA) before and after administration of lenvatinib treatment. The doses and periods of lenvatinib administration were, respectively, 12 mg/day for 7 days and 8 mg/day for 4 days. In both cases, high-resolution DSA revealed a decrease in dilatation and tortuosity of the tumor vessels. Furthermore, the tumor staining became more refined, and newly formed tiny tumor vessels were observed. Perfusion 4D-CTHA revealed a decrease in arterial blood flow to the tumor by 28.6% (from 487.9 to 139.5 mL/min/100 mg) and 42.5% (from 288.2 to 122.6 mL/min/100 mg) in the two cases, respectively. The cTACE procedure resulted in good lipiodol accumulation and complete response. Patients have remained recurrence-free for 12 and 11 months after the cTACE procedure, respectively. The administration of short-term lenvatinib in these two cases resulted in the normalization of tumor vessels, which likely led to improved lipiodol accumulation and a favorable antitumor effect. [ABSTRACT FROM AUTHOR]

Simple Summary: To date, the indication for transarterial chemoembolization (TACE) of intermediate stage hepatocellular carcinoma (HCC) with a high tumor burden remains controversial. TACE has the advantage of a high possibility of achieving complete response (CR). This study aimed to clarify prognosis and identify predictors of CR by TACE in intermediate stage HCC beyond up-to-7 criteria. Overall, 56.9% of patients obtained CR, which contributed to prolonging survival. On multivariate analysis, the predictor of CR was HCC within up-to-11 criteria. In this study, the treatment strategy for intermediate stage HCC based on the 7–11 criteria is suggested. Aim: To clarify the prognosis and identify predictors for obtaining a complete response (CR) by transarterial chemoembolization (TACE) in intermediate stage HCC beyond up-to-7 criteria. Methods: Of the 120 patients with intermediate stage HCC who were treated by TACE as the initial treatment from February 2007 to January 2016, 72 finally matched the following inclusion criteria: beyond up-to-7 criteria; Child–Pugh score under 7; and no combined therapy within 4 weeks after the initial TACE. The CR rate and overall survival (OS) were evaluated. Logistic regression analysis was performed to identify predictors of CR. The deterioration of liver function after TACE was also evaluated. Results: The CR rate was 56.9%, and the overall median survival time (MST) was 37.7 months. The MST was 38.7 months in the CR group and 28.0 months in the non-CR group (p = 0.018). HCC within up-to-11 criteria was the only predictor of CR. The CR rate and MST were 70.7% and 37.7 months, respectively, in patients with HCC within up-to-11 criteria and 38.7% and 32.7 months, respectively, in the patients beyond up-to-11 criteria. Deterioration of the Child–Pugh score after the initial TACE and the 2nd TACE occurred in 24.2% and 12.0%, respectively, and deterioration of the modified albumin-bilirubin (mALBI) grade occurred in 17.6% and 7.4%, respectively. Conclusion: TACE can achieve high CR rates with prolonged overall survival for intermediate stage HCC beyond up-to-7 criteria. The predictor of CR was within up-to-11 criteria. Deterioration of liver function was not severe, but requires caution. Multidisciplinary approach as additional treatment after TACE is important. [ABSTRACT FROM AUTHOR]

Background: This study assessed the differences in daily virus reduction and the residual infectivity after the recommended home stay period in Japan in patients infected with influenza and treated with baloxavir (BA), laninamivir (LA), oseltamivir (OS), and zanamivir (ZA). Methods: We conducted an observational study on children and adults at 13 outpatient clinics in 11 prefectures in Japan during seven influenza seasons from 2013/2014 to 2019/2020. Virus samples were collected twice from influenza rapid test-positive patients at the first and second visit 4–5 days after the start of treatment. The viral RNA shedding was quantified using quantitative RT-PCR. Neuraminidase (NA) and polymerase acidic (PA) variant viruses that reduce susceptibility to NA inhibitors and BA, respectively, were screened using RT-PCR and genetic sequencing. Daily estimated viral reduction was evaluated using univariate and multivariate analyses for the factors such as age, treatment, vaccination status, or the emergence of PA or NA variants. The potential infectivity of the viral RNA shedding at the second visit samples was determined using the Receiver Operator Curve based on the positivity of virus isolation. Results: Among 518 patients, 465 (80.0%) and 116 (20.0%) were infected with influenza A (189 with BA, 58 with LA, 181 with OS, 37 with ZA) and influenza B (39 with BA, 10 with LA, 52 with OS, 15 with ZA). The emergence of 21 PA variants in influenza A was detected after BA treatment, but NA variants were not detected after NAIs treatment. Multiple linear regression analysis showed that the daily viral RNA shedding reduction in patients was slower in the two NAIs (OS and LA) than in BA, influenza B infection, aged 0–5 years, or the emergence of PA variants. The residual viral RNA shedding potentially infectious was detected in approximately 10–30% of the patients aged 6–18 years after five days of onset. Conclusions: Viral clearance differed by age, type of influenza, choice of treatment, and susceptibility to BA. Additionally, the recommended homestay period in Japan seemed insufficient, but reduced viral spread to some extent since most school-age patients became non-infectious after 5 days of onset. [ABSTRACT FROM AUTHOR]

Simple Summary: Transarterial chemoembolization (TACE) is the recommended treatment for intermediate-stage hepatocellular carcinoma (HCC), and its role as a curative treatment is now greater than previously due to the introduction of targeted molecular and immunotherapies. An important current concern is patient selection in TACE for intermediate-stage HCC, which includes an extremely heterogeneous population. The hepatobiliary phase (HEB) in gadoxetic acid disodium-enhanced MRI (EOB-MRI) is related to β-catenin, so EOB-MRI could be a molecular imaging biomarker reflecting tumor biology. Although HCC with signal heterogeneity in the HBP of EOB-MRI showed malignant behavior, no previous study has evaluated prognosis after TACE based on signal heterogeneity quantified in the HBP of EOB-MRI. In this study, we showed a quantitative analysis of tumor signal heterogeneity in HBP on EOB-MRI was valuable in predicting the prognosis after TACE and suggested a treatment strategy for patients with intermediate-stage HCC based on this quantitative evaluation. Background: In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). Methods: This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. Results: A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). Conclusion: CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE. [ABSTRACT FROM AUTHOR]

IntroductionAt present, adenoviral vectors have been widely used for gene transfer into tumor cells primarily because they can be produced in high titers and can infect many different cell types. However, a major problem when utilizing the adenoviral vectors for gene therapy applications is thought to be related to low transduction efficiency due to weak expression of the adenovirus receptor, coxsackie– adenovirus receptor (CAR) in cancer cells, or side effects due to expression of CAR in normal cells. There is an urgent requirement to improve the specificity of gene delivery via adenoviral vectors in the context of cancer gene therapy.Experimental designWe constructed a fiber modified Ad5 vector (Adv-FZ33) in which a IgG-binding domain (Z33) derived from staphylococcal protein A was inserted into the HI loop of knob protein. We then evaluated on both in vitro and in vivo levels the extent of retargeting towards and therapeutic effectiveness against CEA-positive gastric cancers when using the fully human CEA antibody (C2-45) complex with this modified vector.ResultsIn vitro LacZ or EGFP reporter gene expression after infection with Adv-FZ33 vectors conjugated to anti-CEA mAb was approximately 20 times higher than that obtained with vector conjugated to the control mAb (human IgG4). We generated Ax3CAUP-FZ33, which is an Adv-FZ33 derivative vector expressing a therapeutic gene, namely E. coli uracil phosphoribosyltransferase (UPRT) which converts 5FU directly to 5-fluorouridine monophosphate. When conjugated with the anti-CEA mAb, C2-45, Ax3CAUP-FZ33 enhanced the cytotoxicity of 5FU (19.7-fold in terms of IC50 values) against gastric cancer cells. In a nude mouse peritoneal dissemination model, use of Ax3CAUP- FZ33 conjugated with anti-CEA mAb C2-45, in combination with 5FU administration, resulted in greatly enhanced anti-tumor effects against CEA-positive cancer cells. Tumor growth in mice treated with Ax3UP-FZ33/C2-45/5FU was significantly suppressed, and tumor volumes were less than a quarter of those of the control IgG4 group (total weight, 0.12 ± 0.11 g; P < 0.05). Furthermore, we examined the survival effects of Ax3UP-FZ33 conjugated with anti- CEA mAb plus 5FU in mice with peritoneal disseminated gastric cancer. The median survival time of the Ax3CAUP-FZ33/C2-45/5FU group was significantly longer than those of the PBS and 5FU only treatment groups (p<0.01, versus PBS and 5FU only groups). On the other hand, no significant difference was present between the Ax3CAUP-FZ33/5FU or Ax3CAUP-FZ33/IgG4/5FU groups and the PBS or 5FU only groups.ConclusionsThese data suggest that CEA-targeted FZ33-mutant adenovirus- mediated gene delivery offers a strong and selective therapeutic modality against CEA-producing cancers. This novel strategy may be a promising tool for cancer gene therapy.Molecular Therapy (2006) 13, S114–S115; doi: 10.1016/j.ymthe.2006.08.355 [ABSTRACT FROM AUTHOR]

We report valuable imaging findings in a case of β-catenin-activated hepatocellular adenoma (β-HCA) with weak β-catenin activation. A 40 year-old female presented with a liver tumor in S8 that was incidentally detected on ultrasonography. The tumor showed marked enhancement and early venous drainage into the middle hepatic vein in the arterial phase of contrast-enhanced computed tomography (CT). The tumor revealed slight hypointensity in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). Six months after detection, the tumor had increased in size and a biopsy indicated hepatocellular carcinoma. The tumor was resected and pathologically diagnosed as β-HCA with weak β-catenin activation such as exon 3 S45 mutation and exon 7/8 mutation. Marked enhancement in the arterial phase of CT and MRI is a characteristic finding of β-HCA with weak β-catenin activation. Furthermore, the degree of β-catenin activation might determine the signal intensity of β-HCA in the hepatobiliary phase of EOB-MRI. [ABSTRACT FROM AUTHOR]

Context: Few reports focused on the sex differences in alopecia areata (AA) treated with steroid pulse therapy. Aims: This study aimed to investigate the association between the clinical outcomes and distinction of gender in AA patients treated with steroid pulse therapy. Settings and Design: This study retrospectively investigated 32 cases (15 males and 17 females) treated with steroid pulse therapy at the Department of Dermatology at the Shiga University of Medical Science between September 2010 and March 2017. Methods and Material: The administration of corticosteroid was 500 mg methylprednisolone intravenous infusion for 3 consecutive days. Patients were followed up approximately once a month until March 2017. Statistical Analysis Used: The respective data were analyzed by examining and comparing males and females. Statistical analysis was performed using t-test and χ2 test. Results: There were no significant differences in periods from the onset of AA to the administration of steroid pulse therapy (P = 0.2), the degree of severity (P = 0.37) and improved rate (P = 0.0772) between males and females. In contrast, the remission rate was 20% (3 of 15 males) and 71% (12 of 17 females), which was statistically significant (P = 0.0042). Previous reports have also shown a significant difference in the remission rate between males and females (males: 32 of 114; females: 51 of 117; P = 0.014). Conclusions: Despite the limitations of a small sample size including the previous reports (n = 261), female patients with AA would have better outcomes than male patients after steroid pulse therapy. [ABSTRACT FROM AUTHOR]

The microstructure of rapidly solidified melt-spun ribbons of (Fe 0.75 M 0.10 B 0.15 ) 100− x Cu x (M = Si, Zr) alloys was investigated focusing on amorphous-phase formation and the solidification structure. In this study, Fe–Cu–Si–B and Fe–Cu–Zr–B alloys were designed to show amorphous-phase formation and liquid-phase separation simultaneously. Amorphous-phase formation was confirmed in both Fe–Cu–Si–B and Fe–Cu–Zr–B alloys. Minor exceptions in a combination map of mixing enthalpy and quaternary predicted phase diagram are acceptable range for designing a quaternary Fe–Cu-based alloy system that shows liquid-phase separation in Fe-based and Cu-based liquids and the formation of an Fe-based amorphous phase. [ABSTRACT FROM AUTHOR]

The microstructure of nanoglobules with a core–shell structure embedded in an Fe–Zr–B-based amorphous phase by liquid phase separation was investigated in an Fe–Cu–Zr–B immiscible alloy. Transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and scanning transmission electron microscopy (STEM) studies of the melt-spun ribbon clarified that an fcc Cu nanocrystalline core was covered by a B-enriched Fe-based amorphous shell in the nanoglobules. [ABSTRACT FROM AUTHOR]

The microstructure of arc-melted ingots and rapidly solidified melt-spun ribbons of quaternary Fe–Cu–Nb–B immiscible alloys was investigated, with a focus on amorphous-phase formation and solidification structure. A continuous melt-spun ribbon with an Fe–Nb–B-based amorphous matrix and 10–100 nm diameter fcc -Cu crystalline globules was obtained for the (Fe 0.75 Nb 0.10 B 0.15 ) 80 Cu 20 alloy. [ABSTRACT FROM AUTHOR]

Imipenem/Cilastatin (IPM/CS) is currently used as an embolic agent in transarterial embolization for chronic musculoskeletal pain due to its efficacy of short-term blood flow occlusion. However, due to its off-label use, the development of new materials to substitute IPM/CS is needed. Therefore, investigating the behavior of IPM/CS particles becomes crucial. In this paper, we observed the changes in particle size of IPM/CS when dissolved in phosphate-buffered saline, normal saline, iodinated contrast agent and water. The results indicated that the particle size of IPM/CS ranged from 16 to 57 µm and has fastest hydrolysis rate in iodinated contrast agent. And we analyzed the possible structure of hydrolyzed product of IPM/CS in water at room temperature and 37 ℃ using 1HNMR, HPLC. The results suggested Cilastatin is stable at both temperatures, while Imipenem hydrolyzed to produce slightly different products at different temperatures. [Display omitted] [ABSTRACT FROM AUTHOR]

Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP), treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP) by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p  =  3×10−7, odds ratio = 2, 95% confidence intervals: 1.5–2.6). The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p  =  3×10−9). Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs. [ABSTRACT FROM AUTHOR]

Abstract: The effect of addition of B or C on thermoelectric properties of YbAl3 was investigated. YbAl3 is well known as one of heavy fermion intermetallic compounds, which generally possess relatively large Seebeck coefficient and extremely low electrical resistivity. Yb1.05Al3M x (M=B or C, x =0–0.10) showed almost single phase with AuCu3-type structure. The Seebeck coefficient and electrical resistivity of Yb1.05Al3 were hardly affected by the addition of B or C, which showed that there was no difference in the carrier density among these compounds. The addition of C, or especially B, was effective for the reduction of the thermal conductivity, which was mainly attributed to the reduction of the lattice contribution. As a result, Yb1.05Al3B0.10 showed a maximum ZT of about 0.33 at 323K, which was a little larger than ZT of Yb1.05Al3. [Copyright &y& Elsevier]

The authors have been engaged in the development of a phosphorus recovery system capable of maintaining high recovery efficiencies, with the chemical cost suppressed. This time, they conducted demonstration tests of a fluidized bed magnesium ammonium phosphate reactor provided with a seeder reactor for the supernatant from anaerobic digestion using a pilot experimental plant with a wastewater treatment capacity of 20 m3/d. For the digestion supernatant with a phosphorus concentration of approximately 300 mg/L, the treated water phosphorus concentration was 10 to 25 mg/L, and the phosphorus recovery efficiency was more than 90%. Relative to the chemical cost in the case of magnesium chloride, the chemical cost in the case of magnesium hydroxide is approximately 40%. Thus, with the new system, it was possible to reduce the running cost while maintaining high recovery efficiencies. [ABSTRACT FROM AUTHOR]

Galectins, a family of animal lectins that bind ß-galactoside sugar chains, are thought to have a variety of intra- and extracellular functions. Through a case-control study in the Japanese population and subsequent functional analyses, we previously showed that a functional single nucleotide polymorphism (SNP) in the gene encoding galectin-2 (lectin, galactoside-binding, soluble, 2;LGALS2) is associated with susceptibility to myocardial infarction. As an addition to the genetic information aboutLGALS2reported earlier, we provide here a map of polymorphic sites within an 11-kb region containing the gene encoding a closely related molecule, galectin-1 (lectin, galactoside-binding, soluble, 1;LGALS1). The map includes 14 SNPs and two genetic variations of other types detected in a Japanese population sample. Five of the 14 SNPs were not among those deposited in the dbSNP database in the US National Center for Biotechnology Information and appeared to be novel. We also analyzed linkage disequilibrium (LD) using the 12 SNPs in which minor-allele frequencies were>0.20. Investigation of haplotype structure within theLGALS1locus revealed five common haplotypes covering more than 95% of the test population. One, or a pair, of the SNPs described here might serve as a “tag” for detecting associations between complex diseases and genes in this local segment of chromosome 22q13.1. [ABSTRACT FROM AUTHOR]

Palladium nanoparticles encapsulated into graphite (Pd–graphite intercalation compound: Pd–GIC) were produced from two kinds of graphite, natural graphite (average flake size: 270 μm) and kish graphite (average flake size: 15 μm). Hydrogen storage properties of Pd–GIC have been investigated by means of differential scanning calorimetry (DSC) between 473 and 573 K at 1.0 MPa hydrogen pressure. It is found from the DSC measurement that Pd–GIC can absorb and emit hydrogen. [Copyright &y& Elsevier]

The decay of nano-islands on the surface of a Au(111) electrode, in contact with 50 mM sulfuric acid aqueous solution under an applied potential in the range of 0.15–1.2 V, has been investigated using electrochemical atomic force microscopy (EC-AFM). The results are compared with those previously obtained for Au(100). With either orientation, it is found that the area of the top layer of multi-layered islands decreases linearly with time at any applied potential. It was also found that the decay rate, defined as the rate of decrease of the number of atoms in the top-layer of the islands per second, increases with the magnitude of the applied potential. Further, the decay rate of the top layer of the islands on Au(111) is almost the same as that on Au(100). [Copyright &y& Elsevier]

Axin, an important regulator of β-catenin, is frequently mutated in human hepatocellular carcinomas (HCCs), and transduction of the wild-type Axin gene (AXIN1) induces apoptosis in HCC cells as well as in colon cancer cells. To investigate the detailed biological function of Axin, we searched on a cDNA microarray for genes whose expression was altered by transfer of wild-type AXIN1 into colon-cancer cell line LoVo. Among the genes showing altered expression, we focused on one, termed AXUD1 (AXIN1 up-regulated1), that revealed enhanced expression in response to exogeneously expressed AXIN1 but not to LacZ, a control gene. The AXUD1 gene consists of five exons and encodes a transcript with an open reading frame of 1767 bp. A 3.2-kb transcript of AXUD1 was expressed in all human tissues examined, most abundantly in lung, placenta, skeletal muscle, pancreas and leukocyte. By radiation-hybrid mapping we assigned its chromosomal location at 3p22, a region where frequent loss of heterozygosity has been reported in lung, renal, prostate, breast and cervical cancers. AXUD1 was frequently down-regulated in lung, kidney, liver and colon cancers compared with their corresponding normal tissues, suggesting that AXUD1 may have a tumor-suppressor function in those organs. Oncogene (2001) 20, 5062–5066. [ABSTRACT FROM AUTHOR]