Fe-Sn nanocrystalline films for flexible magnetic sensors with high thermal stability.

The interplay of magnetism and spin-orbit coupling on an Fe kagome lattice in Fe3Sn2 crystal produces a unique band structure leading to an order of magnitude larger anomalous Hall effect than in conventional ferromagnetic metals. In this work, we demonstrate that Fe-Sn nanocrystalline films also exhibit a large anomalous Hall effect, being applicable to magnetic sensors that satisfy both high sensitivity and thermal stability. In the films prepared by a co-sputtering technique at room temperature, the partial development of crystalline lattice order appears as nanocrystals of the Fe-Sn kagome layer. The tangent of Hall angle, the ratio of Hall resistivity to longitudinal resistivity, is maximized in the optimal alloy composition of close to Fe3Sn2, implying the possible contribution of the kagome origin even though the films are composed of nanocrystal and amorphous-like domains. These ferromagnetic Fe-Sn films possess great advantages as a Hall sensor over semiconductors in thermal stability owing to the weak temperature dependence of the anomalous Hall responses. Moreover, the room-temperature fabrication enables us to develop a mechanically flexible Hall sensor on an organic substrate. These demonstrations manifest the potential of ferromagnetic kagome metals as untapped reservoir for designing new functional devices.

Type-1 polarised dendritic cells are a potent immunogen against Mycobacterium tuberculosis.

OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1ß, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1ß, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6). RESULTS: Although DC1s from TB patients expressed the same levels of multiple co-stimulatory molecules (CD83, CD86, CD80 and CD40) as the standard DCs (sDCs), DC1s secreted substantially higher levels of IL-12p70. Furthermore, when DCs pulsed with or without ESAT-6 were cultured with lymphocytes from the same patients, DC1s induced much higher numbers of ESAT-6-specific IFN-γ-producing T-cells than sDCs, as manifested by their superior induction of natural killer cell activation and antigen-independent suppression of regulatory T-cells. CONCLUSION: TB antigen-loaded DC1s are potent inducers of antigen-specific T-cells, which could be used to develop improved immunotherapies of TB.

Ultraconserved region-containing Transformer 2ß4 controls senescence of colon cancer cells.

Ultraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2ß (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2ß4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2ß4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2ß4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem-loop structure, blocked the interaction with Sp1 and increased CDKN1A transcription. Overexpression of TRA2ß4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects. Taken together, TRA2ß4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program. This novel function of TRA2ß4 may uncover an oncogenic function of transcribed UCRs.

Ultrasound-guided percutaneous aspiration of hyperreactio luteinalis avoids laparoscopic untwisting of ovarian torsion.

Hyperreactio luteinalis (HL) is characterized by multicystic bilateral enlargement of the ovaries and is a self-limiting benign condition associated with pregnancy or trophoblastic disease. Since HL regresses spontaneously over time, it should be managed conservatively as long as the patient's condition permits; torsion of the enlarged ovaries is believed to be the only exception that mandates surgical intervention. Here, we describe a case of HL complicated by ovarian torsion that was treated successfully without surgical intervention. A 33-year-old woman was admitted to our hospital owing to acute abdomen. Nine days previously, she had had a stillbirth caused by hydrops fetalis at 24 weeks' gestation. The characteristic findings observed on magnetic resonance imaging (MRI) led to the diagnosis of HL complicated by torsion of the enlarged left ovary. Emergency laparoscopic detorsion of the ischemic left ovary was planned. Aiming to reduce the risk of cystic injury and bleeding at the trocar insertion site, volume reduction of the left ovarian cyst was performed by percutaneous aspiration. The patient's pain diminished rapidly and laparoscopic surgery was deferred. Subsequent MRI revealed that gadolinium enhancement of the left ovarian tumor had been restored, indicating spontaneous detorsion of the left ovary. The patient remained asymptomatic and was discharged from the hospital 12 days after aspiration of the cyst. From this experience, we propose that, in cases of ovarian torsion occurring in large functional cysts, including HL, volume reduction by percutaneous cyst aspiration should be considered before performing emergency laparoscopic surgery.

Transformer 2ß and miR-204 regulate apoptosis through competitive binding to 3' UTR of BCL2 mRNA.

RNA-binding proteins and microRNAs are potent post-transcriptional regulators of gene expression. Human transformer 2ß (Tra2ß) is a serine/arginine-rich-like protein splicing factor and is now implicated to have wide-ranging roles in gene expression as an RNA-binding protein. RNA immunoprecipitation (RIP) with an anti-Tra2ß antibody and microarray analysis identified a subset of Tra2ß-associated mRNAs in HCT116 human colon cancer cells, many of which encoded cell death-related proteins including Bcl-2 (B-cell CLL/lymphoma 2). Tra2ß knockdown in HCT116 cells decreased Bcl-2 expression and induced apoptosis. Tra2ß knockdown accelerated the decay of BCL2α mRNA that encodes Bcl-2 and full-length 3' UTR, while it did not affect the stability of BCL2ß mRNA having a short, alternatively spliced 3' UTR different from BCL2α 3' UTR. RIP assays with anti-Tra2ß and anti-Argonaute 2 antibodies, respectively, showed that Tra2ß bound to BCL2α 3' UTR, and that Tra2ß knockdown facilitated association of miR-204 with BCL2α 3' UTR. The consensus sequence (GAA) for Tra2ß-binding lies within the miR-204-binding site of BCL2 3' UTR. Mutation of the consensus sequence canceled the binding of Tra2ß to BCL2 3' UTR without disrupting miR-204-binding to BCL2 3' UTR. Transfection of an anti-miR-204 or introduction of three-point mutations into the miR-204-binding site increased BCL2 mRNA and Bcl-2 protein levels. Inversely, transfection of precursor miR-204 reduced their levels. Experiments with Tra2ß-silenced or overexpressed cells revealed that Tra2ß antagonized the effects of miR-204 and upregulated Bcl-2 expression. Furthermore, TRA2ß mRNA expression was significantly upregulated in 22 colon cancer tissues compared with paired normal tissues and positively correlated with BCL2 mRNA expression. Tra2ß knockdown in human lung adenocarcinoma cells (A549) increased their sensitivity to anticancer drugs. Taken together, our findings suggest that Tra2ß regulates apoptosis by modulating Bcl-2 expression through its competition with miR-204. This novel function may have a crucial role in tumor growth.

He/Ar-atom scattering from molecular monolayers: C60/Pt(111) and graphene/Pt(111).

Supersonic He and Ar atomic beam scattering from C(60) and graphene monolayers adsorbed on a Pt(111) surface are demonstrated in order to obtain detailed insight into a gas-molecule collision that has not been studied in detail so far. The effective masses and phonon spectral densities of the monolayers seen by different projectiles are discussed based on classical models such as the hard cube model and the recently developed smooth surface model. Large effective masses are deduced for both the monolayers, suggesting collective effects of surface atoms in the single collision event. The effective Debye temperature of graphene was found to be similar to that reported in highly oriented pyrolytic graphite (HOPG), indicating that the graphene is decoupled well from the Pt substrate. A much smaller Debye-Waller factor was found for the C(60) layer, probably reflecting the strong C(60)-Pt(111) interaction.

Induction and emergence behavior of children undergoing general anesthesia correlates with maternal salivary amylase activity before the anesthesia.

BACKGROUND: The parents of the children who undergo surgery experience stress during the pre-anesthetic period. Such stress influences the mental status of their children, thereby inducing their pre-anesthetic anxiety and problematic behavior at emergence. Recently, measurement of salivary biomarkers was evaluated as stress biomarkers. Especially, alpha-amylase is utilized as an excellent index for psychological stress. In the present study, we tested whether salivary amylase activity of mothers before the surgery of their children correlates with the peri-operative children's behaviors. METHODS: A total of 22 pairs of mothers and children were analyzed. Maternal salivary amylase activity was evaluated at the entrance of the operation room. The children underwent minor plastic surgery under general anesthesia, and induction and emergence behaviors were assessed. RESULTS: The higher the maternal salivary amylase activity, the severer the children's induction anxiety (r(s)=-0.667, n=22, P<0.0001), and the higher the maternal amylase activity, the severer the children's emergence agitation (r(s)=0.705, n=22, P<0.0001). CONCLUSION: Induction and emergence behaviors of children undergoing general anesthesia significantly correlated with their respective maternal salivary amylase activity during the pre-anesthetic period.

Combined medical and surgical treatment of severe vernal keratoconjunctivitis.

PURPOSE: We report the efficacy of an alternative method of treatment for vernal keratoconjunctivitis (VKC) that consists of excision of the palpebral conjunctiva followed by supratarsal injection of corticosteroid and five times daily topical application of 0.05% cyclosporine A (CsA) and cromolyn sodium. METHODS: We evaluated 10 patients with severe treat-resistant VKC with corneal complications. The patients were evaluated for symptoms and for signs, including conjunctival changes, corneal limbal infiltrates, vascularization, reduction of epitheliopathy, meibomitis, visual acuity, intraocular pressure, and pathologic evaluation, before and after treatment. RESULTS: All patients showed marked improvement after 2 weeks of treatment. The symptoms (P <.01), signs (P <.02), and the visual acuity of all patients (P <.01) had significantly improved following treatment. Histological examination showed significant inflammatory cell decreases 4 weeks after surgery (P <. 05). CONCLUSION: Surgery plus topical drug therapy may be useful in treating patients with very severe VKC.

Characterization of rat OX40 ligand by monoclonal antibody.

OX40 (CD134) is a member of the tumor necrosis factor (TNF) receptor superfamily first identified as a rat T cell activation marker. We previously identified the rat ligand for OX40 (OX40L) by molecular cloning. In the present study, we newly generated an anti-rat OX40L mAb (ATM-2) that can inhibit the binding of OX40 to rat OX40L and thus efficiently inhibits the T cell costimulatory activity of rat OX40L. Flow cytometric analyses using ATM-2 and an anti-rat OX40 mAb (MRC OX40) indicated that OX40 was inducible on splenic CD4(+) T cells by stimulation with immobilized anti-CD3 mAb, while OX40L was not expressed on resting or activated T cells. OX40L was expressed on splenic B cells after stimulation with lipopolysaccharide (LPS), but not on peritoneal macrophages. Interestingly, splenic dendritic cells (DC) expressed OX40L constitutively, which was further upregulated by LPS stimulation. The potent costimulatory activities of splenic DC for anti-CD3-stimulated rat CD4(+) T cell proliferation and cytokine (IL-2, IFN-gamma, IL-10, and IL-13) production were substantially inhibited by ATM-2. These results indicated that OX40L is expressed on professional antigen-presenting cells (APC), and may be involved in humoral immune responses via T-B interaction and in cellular immune responses via T-DC interaction in the rat system.

[Long-term prognosis of ulcerative colitis].

Despite its intermittent course of activity and remission, the good response to salazopyridine and steroids makes the long-term prognosis of ulcerative colitis favorable. The number of non-active type ulcerative colitis is increasing and consequently, the rate of active disease and relapse is decreasing every year. More than 90% of the patients even with disease of 10 or more years are able to work almost with no limits for the daily living. The colectomy rate in Japan is 4.1% after one year of the onset of the disease and 6.8% after 2 years. Thereafter approximately 1% of the patients undergo surgery yearly. The most common reasons of surgery are complications such as massive bleeding, perforation or toxic megacolon. Other indications are chronic continuous disease and cases with frequent relapses. Considering the extension of the disease, about one-third of the total colitis type and 10% of the left-sided type undergo surgery. The risk of colonic cancer is higher in patients with total colitis type and when has had the disease for more than 10 years. Most of the them are flat type poor-differentiated adenocarcinomas. Therefore patients with total colitis type for more than 10 years should undergo colonoscopic surveillance.

Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation.

BACKGROUND: Conditions that destroy the limbal area of the peripheral cornea, such as the Stevens-Johnson syndrome, ocular pemphigoid, and chemical and thermal injuries, can deplete stem cells of the corneal epithelium. The result is scarring and opacification of the normally clear cornea. Standard corneal transplantation cannot treat this form of functional blindness. METHODS: We performed and evaluated 70 transplantations of corneal epithelial stem cells from cadaveric eyes into 43 eyes of 39 patients with severe ocular-surface disorders and limbal dysfunction. Medical treatment had failed in all patients. The patients had a mean preoperative visual acuity of 0.004 (only being able to count the number of fingers presented by the examiner) in the affected eyes, which satisfies the criteria for legal blindness in most countries. In 28 eyes, we also performed standard corneal transplantation. Stem-cell transplantations were performed as many as four times on 1 eye if the initial results were not satisfactory; 19 eyes had multiple transplantations. Patients were followed for at least one year after transplantation. RESULTS: A mean of 1163 days after stem-cell transplantation, 22 of the 43 eyes (51 percent) had corneal epithelialization; of the 22 eyes, 7 eyes had corneal stromal edema and 15 eyes had clear corneas. Mean visual acuity improved from 0.004 to 0.02 (vision sufficient to distinguish the largest symbol on the visual-acuity chart from a distance of 1 m) (P<0.001). The 15 eyes in which the cornea remained clear had a final mean visual acuity of 0.11 (the ability to distinguish the largest symbol from a distance of 5 m). Complications of the first transplantation included persistent defects in the corneal epithelium in 26 eyes, ocular hypertension in 16 eyes, and rejection of the corneal graft in 13 of 28 eyes. The epithelial defects eventually healed in all but two of the eyes. CONCLUSIONS: Transplantation of corneal epithelial stem cells can restore useful vision in some patients with severe ocular-surface disorders.

A new surgical technique for deep lamellar keratoplasty with single running suture adjustment.

PURPOSE: To improve the technique of deep lamellar keratoplasty. METHODS: For the recipient eye, a divide-and-conquer technique was applied to deep lamellar keratoplasty. After trephinization, the recipient cornea within the trephine was divided into four quadrants to facilitate lamellar dissection at approximately 70% depth. This procedure of division was continued until the Descemet membrane was exposed in the central area. The corneal graft was placed with an adjusted single running suture. Seventeen eyes were treated with this technique. RESULTS: In 17 eyes of 15 patients, the mean visual acuity 6 months or more after deep lamellar keratoplasty was 20/52 with eyeglass correction and 20/80 without eyeglass correction. At 6 months or more after deep lamellar keratoplasty, the mean +/- SD keratometric astigmatism in 17 eyes was 3.2 +/- 2.3 diopters. CONCLUSION: This technique facilitates deep lamellar keratoplasty and prevents high or excessive astigmatism after surgery.

Surgical reconstruction of the ocular surface in advanced ocular cicatricial pemphigoid and Stevens-Johnson syndrome.

PURPOSE: Ocular cicatricial pemphigoid and Stevens-Johnson syndrome often cause ocular damage and blindness not amenable to surgical correction. We present a new surgical technique for reconstructing affected eyes. METHODS: Fourteen eyes of 11 patients with cicatricial keratoconjunctivitis (seven patients with cicatricial pemphigoid and four with Stevens-Johnson syndrome; average age +/- S.D., 55.5 +/- 25.4 years) were treated with a combination of allograft limbal transplantation, amniotic membrane transplantation, and tarsorrhaphy, followed every 15 minutes by artificial tears derived from the patient's blood serum. Eight eyes required concomitant penetrating or lamellar keratoplasty because of corneal opacity. RESULTS: With a mean follow-up of 143 days (range, 10 to 608 days), we achieved successful ocular surface reconstruction in 12 eyes, with minimal recurrence of symblepharon. Failure occurred in two eyes (one each in 9- and 10-year-old boys) that developed corneal infiltration and vascularization. CONCLUSIONS: A combination of allograft limbal transplantation, amniotic membrane transplantation, and tarsorrhaphy, followed by the use of serum-derived tears, can reconstruct the ocular surface in most cases. Although in this study the follow-up period was short and relatively few patients were studied, this approach appears to offer an alternative to keratoprosthesis for treating severe cicatricial keratoconjunctivitis with dry eye.

[Early colorectal cancer].

Early colorectal cancer is situated at the field with a rich stock of topics in Japan. For this reason, there are increasing number of patients with colorectal cancer, many reports of depressed early cancer and rapid advances of molecular biology about colorectal neoplasm. Most of early colorectal cancers are discovered to be the protruded type by all accounts in spite that many cases of depressed type early cancer have been reported in many Japanese institutes. The final diagnosis of early colorectal cancer is usually made by histological examination after endoscopic resection, however invasive cancers with distinct endoscopic appearance of submucosal spread should be treated surgically from the beginning after diagnosis on biopsy specimens.

Common T cell receptor clonotype in lacrimal glands and labial salivary glands from patients with Sjögren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltration into lacrimal and salivary glands leading to symptomatic dry eyes and mouth. Immunohistological studies have clarified that the majority of infiltrating lymphocytes around the lacrimal glands and labial salivary glands are CD4 positive alphabeta T cells. To analyze the pathogenesis of T cells infiltrating into lacrimal and labial salivary glands, we examined T cell clonotype of these cells in both glands from four SS patients using PCR-single-strand conformation polymorphism (SSCP) and a sequencing method. SSCP analysis showed that some infiltrating T cells in both glands expand clonally, suggesting that the cells proliferate by antigen-driven stimulation. Intriguingly, six to sixteen identical T cell receptor (TCR) Vbeta genes were commonly found in lacrimal glands and labial salivary glands from individual patients. This indicates that some T cells infiltrating into both glands recognize the shared epitopes on autoantigens. Moreover, highly conserved amino acid sequence motifs were found in the TCR CDR3 region bearing the same TCR Vbeta family gene from four SS patients, supporting the notion that the shared epitopes on antigens are limited. In conclusion, these findings suggest that some autoreactive T cells infiltrating into the lips and eyes recognized restricted epitopes of a common autoantigen in patients with SS.

A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia.

A 2-year-old girl with a very rare form of acute megakaryoblastic leukemia (AMKL), having the 11p13;14q11 translocation specific for T-cell malignancies, is reported. She was diagnosed as having AMKL on the basis of her bone marrow, which contained 30% megakaryoblasts identified by characteristic morphology on May-Giemsa stain, positive for platelet peroxidase activity and for the surface marker of platelet glycoprotein IIb/IIIa, CD41. Cytogenetic studies of marrow cells revealed 47,XX,i(7q), +der(11)t(11;14)(p13;q11), -14, +21. She achieved hematologic remission after two courses of chemotherapy including behenoyl cytarabine, acracinorubicin, 6 mercaptopurine, and prednisolone, but soon relapsed and died 11 months after admission. This case suggests that adequate diagnostic assessments of morphology, surface markers, and cytogenetics are necessary for proper diagnosis in leukemia and lymphoma, and that an important, though as-yet unidentified, gene in megakaryopoiesis may reside in the 14q11 chromosomal region.

Isolation of anti-Beijing-1 group-specific monoclonal antibody and antigenic analysis of Japanese encephalitis viruses in India.

Based on the reactivities of monoclonal antibodies, we previously reported that 25 Japanese encephalitis (JE) virus strains fell into five antigenic groups: Nakayama, Beijing-1, Kamiyama, 691004 and Muar. In the present study, we produced monoclonal antibodies against the Beijing-1 strain and obtained the Beijing-1 group-specific antibody, designated BEGMA 1. Furthermore, antigenic comparison of the seven JE virus strains isolated in India was performed by using BEGMA 1 and other group-specific antibodies. The results showed that six strains fell into the Kamiyama group to which the currently prevalent strains in Japan belong.