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A conduit for peripheral nerve regeneration (NERBRIDGE®; Toyobo Co., Japan) in cases of disconnection or deficiency of the peripheral nerve was approved in Japan in 2013. NERBRIDGE® is a polyglycolic acid-collagen (PGA) product derived from porcine skin. The use of NERBRIDGE® has been reported mainly in orthopaedic surgery. Reports on its use for sensory nerve injuries in the oral region are scarce. This case report describes a case of significant sensory recovery obtained by nerve repair using NERBRIDGE® in a patient with schwannoma-induced inferior alveolar nerve resection. At the 1-year postoperative evaluation, sensory nerve recovery using the two-point discrimination test was confirmed.

Here we consider the following functional equation, Ψ ( X ( t , x , Ψ ( x ) ) ) = Y ( t , x , Ψ ( x ) ) , where X ( t , x , y ) and Y ( t , x , y ) are holomorphic functions in t < θ , | x | < θ , ...

Vessel sealing devices have been described to be effective, allowing to perform procedures with reduced blood loss and shorter operative times in head and neck surgery. Since the traditional vessel sealing devices are all disposable and expensive, there are not often used even in advanced cancer surgery in terms of cost. On the other hand, ‘marClampCut IQ’ (KLS Martin, Tuttlingen, Germany) is a new reusable vessel sealing device. In this clinical study, a traditional disposable device ‘LigaSure small jaw’ and a reusable device ‘marClampCut IQ’ were particularly compared regarding medical expenses and efficacy in modified total neck dissection. Between October 2014 and April 2020, modified total neck dissections were performed using the ‘LigaSure small jaw’ for 56 patients aged from 26y/o to 88y/o (median:66.0y/o). The ‘marClampCut IQ’ was mainly used between November 2018 and April 2020 for 64 modified total neck dissections in patients aged from 31y/o to 91y/o (median:70.5y/o). The amount of blood loss was significantly more in the ‘LigaSure small jaw’ group than in the ‘marClampCut IQ’ group (U-test, P = 0.006). There were no significant differences in age and operation time between the ‘LigaSure small jaw’ group and the ‘marClampCut IQ’ group. When calculated based on the list price in Japan, ‘LigaSure small jaw’ costed $1,000 each; on the other hand, ‘marClampCut IQ’ costed $240 per operation. We found that we could save $760 per operation using ‘marClampCut IQ’. The new reusable device ‘marClampCut IQ’ provided similar clinical efficacy and safety with a highly reduced cost when compared to the disposable device ‘LigaSure small jaw’ in this clinical study of modified total neck dissection.

Objetivo: Identificar na literatura os impactos da violência doméstica na vida das mulheres. Métodos: Trata-se de revisão integrativa realizada em seis fases. A busca ocorreu nas bases de dados LILACS, BDENF e MEDLINE, via portal da Biblioteca Virtual em Saúde, no mês de janeiro de 2023. Resultados: Foram identificados 277 estudos, dos quais 10 foram eleitos. A partir da análise do escopo da produção científica nacional sobre a violência doméstica contra a mulher, optou-se por apresentar os resultados e discussões por meio da construção de unidades temáticas. Assim surgiram três unidades temáticas intituladas: Identificação, notificação e conduta frente a violência contra a mulher e Perfil e característica de mulheres vítimas de violência. Considerações finais: Diante do exposto, percebe-se que a violência contra a mulher continua sendo, na contemporaneidade, um fato presente em nossa sociedade, atingindo em maior proporção as classes sociais mais baixas, que sofrem historicamente com a violência e com a marginalização.

UDP-apiose, a donor substrate of apiosyltransferases, is labile because of its intramolecular self-cyclization ability, resulting in the formation of apiofuranosyl-1,2-cyclic phosphate. Therefore, stabilization of UDP-apiose is indispensable for its availability and identifying and characterizing the apiosyltransferases involved in the biosynthesis of apiosylated sugar chains and glycosides. Here, we established a method for stabilizing UDP-apiose using bulky cations as counter ions. Bulky cations such as triethylamine effectively suppressed the degradation of UDP-apiose in solution. The half-life of UDP-apiose was increased to 48.1 ± 2.4 h at pH 6.0 and 25 °C using triethylamine as a counter cation. UDP-apiose coordinated with a counter cation enabled long-term storage under freezing conditions. UDP-apiose was utilized as a donor substrate for apigenin 7-O-β-D-glucoside apiosyltransferase to produce the apiosylated glycoside apiin. This apiosyltransferase assay will be useful for identifying genes encoding apiosyltransferases.

In this study, we examined the covering effect of a new kind of infrared ray (IR)-cutting net to improve the low yield of summer-sown spinach crops in greenhouse. This IR-cutting net gives about 61% transmittance of visible light and approx. 50–54% absorbance of IR from 700 to 2600 nm. The utilisation of IR-cutting net in summer could favour plant growth due to lowering greenhouse temperatures. The globe temperatures when shielded by the IR-cutting net were approx. 6–8oC lower than without the net, an effect nearly equal to that of a 50% shade net. Although the plant growth was significantly reduced when plants were grown without a net, the crop productivity was intensified more by covering with the IR-cutting net than the 50% shade net. Mean fresh weight and yield for the IR-cutting net treatment was approx. 1.6 and 1.3 times larger, respectively, than for the 50% shade net. Although the photosynthetic capacity of plants grown without a net is suppressed by high temperature, this decreased photos...

Recent advance of bioinformatics and analytical apparatuses such as next generation DNA sequencer (NGS) and mass spectrometer (MS) has brought a big wave of comprehensive study to biology. Comprehensive study targeting all genes, transcripts (RNAs), proteins, metabolites, hormones, ions or phenotypes is called genomics, transcriptomics, proteomics, metabolomics, hormonomics, ionomics or phenomics, respectively. These omics are powerful approaches to identify key genes for important traits, to clarify events of physiological mechanisms and to reveal unknown metabolic pathways in crops. Recently, the use of omics approach has increased dramatically in fruit tree research. Although the most reported omics studies on fruit trees are transcriptomics, proteomics and metabolomics, and a few is reported on hormonomics and ionomics. In this article, we reviewed recent omics studies of major fruit trees, i.e. citrus, grapevine and rosaceae fruit trees. The effectiveness and prospects of omics in fruit tree research will as well be highlighted.

Higher relative humidity under elevated CO 2 conditions increases stomatal conductance and is expected to promote photosynthesis and growth of tomato. However, yield increase under higher relative humidity has been often reported to be unstable, depending on the growing conditions. Therefore, we investigated the effect of relative humidity and nutrient supply on growth and nutrient uptake under elevated CO 2 conditions in greenhouse tomato production. In two greenhouses, we grew tomato hydroponically at two electrical conductivity (EC) levels (low EC treatments: 0.8–1.2 dS m −1 , high EC treatments: 1.6–1.9 dS m −1 ). In one greenhouse, we installed a humidification system. The other was designated as a control. The dry weight (DW) per plant tended to increase with humidification though without significant differences. The leaf area per plant was not affected by humidification, but the high EC treatment increased the leaf area. The average water uptake in the low EC with mist decreased compared with that without mist. Our results suggested that water use efficiency was increased by higher humidity, whereas the nutrient content of leaves was suppressed by mist in the low EC. In both the treatments, supplying higher EC levels of nutrient solutions increased N, K and P contents but did not increased Ca or Mg contents as well as in low EC without mist. These results suggest that supplying high EC nutrient solutions cannot increase Ca and Mg contents sufficiently in leaves and stems. To stably increase yield of tomato by humidification under elevated CO 2 conditions, it is important to monitor the transpiration rate and carefully control relative humidity.

Grape (Vitis vinifera) accumulates various polyphenolic compounds, which protect against environmental stresses, including ultraviolet-C (UV-C) light and pathogens. In this study, we looked at the transcriptome and metabolome in grape berry skin after UV-C irradiation, which demonstrated the effectiveness of omics approaches to clarify important traits of grape. We performed transcriptome analysis using a genome-wide microarray, which revealed 238 genes up-regulated more than 5-fold by UV-C light. Enrichment analysis of Gene Ontology terms showed that genes encoding stilbene synthase, a key enzyme for resveratrol synthesis, were enriched in the up-regulated genes. We performed metabolome analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry, and 2,012 metabolite peaks, including unidentified peaks, were detected. Principal component analysis using the peaks showed that only one metabolite peak, identified as resveratrol, was highly induced by UV-C light. We updated the metabolic pathway map of grape in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and in the KaPPA-View 4 KEGG system, then projected the transcriptome and metabolome data on a metabolic pathway map. The map showed specific induction of the resveratrol synthetic pathway by UV-C light. Our results showed that multiomics is a powerful tool to elucidate the accumulation mechanisms of secondary metabolites, and updated systems, such as KEGG and KaPPA-View 4 KEGG for grape, can support such studies.

The Fc region of human IgG1 mediates effector function via binding to Fcγ receptors and complement activation. The H and L chains of IgG1 antibodies are joined by four interchain disulfide bonds. In this study, these bonds within the therapeutic IgG1 rituximab (RTX) were cleaved either by mild reduction followed by alkylation or by mild S-sulfonation; consequently, two modified RTXs – A-RTX (alkylated) and S-RTX (S-sulfonated) – were formed, and both were almost as potent as unmodified RTX when binding CD20 antigen. Unexpectedly, each modified RTX had a higher binding affinity for FcγRIIIA (CD16A) than did unmodified RTX. However, S-RTX and A-RTX were each less potent than RTX in an assay of antibody-dependent cellular cytotoxicity (ADCC). In this ADCC assay, each modified RTX showed decreased secretion of granzyme B, but no change in perforin secretion, from effector cells. These results provide significant information on the structures within IgG1 that are involved in binding FcγRIIIA, and they may be useful in the development of therapeutic antagonists for FcγRIIIA.

Here we consider the following functional equation, $$\Psi(X(x,\Psi(x)))=Y(x, \Psi(x)),$$ where X(x, y) and Y(x, y) are holomorphic functions in |x| < δ1, |y| < δ1. When we consider a nonlinear simultaneous system of two variables difference equations, we can reduce it to a single difference equation of first order by a solution Ψ of the above functional equation. We obtain a matrix by the linear terms of functions X and Y. When the all eigenvalues of the matrix are equal to 1, it is difficult to have a solution of the above functional equation. In the present paper, we derive a formal solution of the above functional equation under the condition. Further we prove the existence of a solution which is holomorphic and have an asymptotically expansion of the formal solution. Moreover, we will show an example of nonlinear difference system such that our results are applicable.

In order to induce horticulturally valuable mutants in the Liliaceous ornamental Tricyrtis hirta, embryogenic calluses of this species were irradiated with 12C+6 ion beams. Morphological characterization was performed on 35, 37 and 15 plants regenerated from calluses irradiated with 5, 10 and 20 Gy ion beams, respectively, and on 10 plants from non-irradiated calluses after 3 years of cultivation in pots. No plants were regenerated from calluses irradiated with 50 Gy ion beams. There were no large differences in the mean values of leaf length, leaf width, soil and plant analyzer development (SPAD) value of leaves, flower length and flower diameter between the control (division-derived plants from the mother plant of the embryogenic calluses) and the irradiation treatments at different doses. On the other hand, the mean number of shoots per plant increased, and the mean shoot length and the mean number of nodes per shoot decreased in the irradiation treatments. The mean number of flowers per plant was increased in the 20 Gy irradiation treatment. For most morphological characteristics investigated, the variation spectrum widened with increase in the irradiation dose. Several horticulturally attractive variations such as dwarfism, slender and deep green leaves, and large flowers were observed in regenerants from the irradiation treatments, and these variations were stable after additional 2 years of cultivation in pots or garden. Thus mutation induction by heavy ion beam irradiation of embryogenic calluses is a valuable tool for improving horticultural value of T. hirta.

Effect of heavy-ion beam irradiation on the growth and development of embryogenic calluses was examined in the liliaceous monocotyledon Tricyrtis hirta and the umbelliferous dicotyledon Daucus carota. Embryogenic calluses of T. hirta were irradiated with 5, 10, 20 or 50 Gy of 12C6+, 14N7+ or 20Ne10+ ions, and those of D. carota were irradiated with 5, 10, 20 or 50 Gy of 14N7+ ions. In both species, irradiation at 10–50 Gy inhibited growth of embryogenic calluses, and callus growth rate decreased as irradiation dose increased. Interestingly irradiation at low doses greatly promoted somatic embryo production from embryogenic calluses in both species. In T. hirta, calluses irradiated with 5 and 10 Gy 12C6+ ions, 10 Gy 14N7+ ions, and 5 Gy 20Ne10+ ions produced more than twice as many embryos as the control, non-irradiated calluses. In D. carota, embryogenic calluses irradiated with 5 Gy 14N7+ ions produced more than one and a half times as many embryos as the control. Somatic embryo production in both species was inhibited by irradiation at 20 and 50 Gy.

The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/.

Here we consider the functional equation $$ \psi(X(x, \psi(x))) = Y(x, \psi(x)),$$ in which X(x, y) and Y (x, y) are holomorphic functions of \((x, y) \in {\mathbb{C}}\) in a neighborhood of (0, 0), and further we will apply it for obtaining general solutions of some nonlinear difference equations.

The case of an isolated right submandibular gland aplasia, detected by computed tomography scan, magnetic resonance imaging, and technetium 99m-pertechnetate scintigraphy, in a 58-year-old man is reported.

The Fc domain of human IgG1 binds to Fcγ receptors (FcγRs) to induce effector functions such as phagocytosis. There are four interchain disulfide bonds between the H and L chains. In this study, the disulfide bonds within the IgG1 trastuzumab (TRA), which is specific for HER2, were cleaved by mild S-sulfonation or by mild reduction followed by S-alkylation with three different reagents. The cleavage did not change the binding activities of TRA to HER2-bearing SK-BR-3 cells. The binding activities of TRA to FcγRIIA and FcγRIIB were greatly enhanced by modification with mild reduction and S-alkylation with ICH2CONH2 or N-(4-aminophenyl) maleimide, while the binding activities of TRA to FcγRI and FcγRIIIA were decreased by any of the four modifications. However, the interchain disulfide bond cleavage by the different modifications did not change the antibody-dependent cell-mediated phagocytosis (ADCP) of SK-BR-3 cells by activated THP-1 cells. The order of FcγR expression levels on the THP-1 cells was FcγRII > FcγRI > FcγRIII and ADCP was inhibited by blocking antibodies against FcγRI and FcγRII. These results imply that the effect of the interchain disulfide bond cleavage on FcγRs binding and ADCP is dependent on modifications of the cysteine residues and the FcγR isotypes.

The Liliaceous perennial Tricyrtis hirta, sometimes called ‘Japanese toad lily’, has recently become popular as an ornamental for pot and garden uses. Highly embryogenic callus cultures of this plant predominately consisted of diploid cells but also contained tetraploid cells after 1 year of establishment. In the present study, plans regenerated from the 1-year-old embryogenic callus cultures were subjected to ploidy level analysis and morphological characterization following 3 years of cultivation. Among 37 plants examined, 28 kept the diploid level (2n = 2x = 26) but nine were tetraploid (2n = 4x = 52) as indicated by FCM analysis and chromosome observation. Although no morphological alterations were detected in 26 out of 28 diploid regenerants, the remaining two showed noticeable variations: both were severely dwarf and had crimped leaves and many malformed flowers. The tetraploid regenerants had several horticulturally attractive characteristics compared with the diploid controls, such as longer shoots, thicker stems, and larger flowers. Thus regeneration of tetraploid plants from 1-year-old embryogenic callus cultures offers a possibility to improve the horticultural value of T. hirta, although regeneration of trueness-to-type plants is essential for utilizing the cultures for micropropagation and genetic transformation.

Human beta1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) is thought to be an enzyme that extends the polylactosamine acceptor chains, but its function and structure analysis are unknown. To obtain insight into the structure of beta3GnT2, the effects of N-glycosylation on its biological function were evaluated using the addition of inhibitors, site-directed mutagenesis of potential N-glycosylation sites, and deletion of its N-terminal region using a fusion protein with GFP(uv) in a baculovirus expression system. Four of five potential N-glycosylation sites were found to be occupied, and their biological function and secretion were inhibited with the treatment of N-glycosylation inhibitor, tunicamycin. The N-glycosylation at Asn219 was necessary for the beta3GnT activity; moreover, N-glycosylation at Asn127 and Asn219 was critical for efficient protein secretion. When Ser221 was replaced with Thr, fusion protein was expressed as a single band, indicating that the double band of the expressed fusion protein was due to the heterogeneity of the glycosylation at Asn219. The truncated protein consisting of amino acids 82-397 (GFP(uv)-beta3GnT2Delta83), which lacked both one N-glycosylation site at Asn79 and the stem region of glycosyltransferase, was expressed as only a small form and showed no beta3GnT activity. These results suggest that the N-glycosylation site at Asn219, which is conserved throughout the beta1,3-glycosyltransferase family, is indispensable not only with regard to its biological function, but also to its secretion. The N-terminal region, which belongs to a stem region of glycosyltransferase, might also be important to the active protein structure.

We report on a 66-year-old man with adenolipoma of the hard palate. The patient consulted our hospitalfor detailed examination of a palatal mass. Magnetic resonance imaging showed a well-delineated tumor in thepalate. Since CT scanning indicated no bone resorption, the tumor was resected en bloc, with the patient undergeneral anesthesia. Histopathological examination suggested adenolipoma. During 4 years 6 months of postoperativefollow-up, the patient's course has been good, without relapse.

Functional analysis using RNAi was performed on eleven genes for metalloproteases of the M12A family inCaenorhabditis elegansand the interference of the C17G1.6 gene (nas-37) was found to cause incomplete molting. The RNAi of the C26C6.3 gene (nas-36) also caused a similar molting defect but not so severely as that of the nas-37 gene. Both the genes encode an astacinlike metalloprotease with an epidermal growth factor (EGF) like domain, a CUB domain, and a thrombospondin-1 domain, in this order. The promoterdriven green fluorescent protein (GFP) expression analysis suggested that they are expressed in hypodermal cells throughout the larval stages and in the vulva of adult animals. In the genetic background of rde-1(ne219), where RNAi does not work, the molting defect caused by the nas-37 interference was observed when the transgenic wildtype rde-1 gene was expressed under the control of the dpy-7 promoter, known to be active in the hypodermal cells, but not under the control of the myo-3 promoter, active in the muscular cells. Therefore these proteases are thought to be secreted by the hypodermal cells and to participate in shedding of old cuticles.

We investigated the effects of YM905 [(+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate], a new orally active muscarinic M3-receptor antagonist, on bowel dysfunction in vivo using experimental models that reproduce the symptoms present in irritable bowel syndrome (IBS). YM905 potently inhibited restraint stress-induced fecal pellet output in fed rats (ED50: 4.0 mg/kg) and diarrhea in fasted rats (ED50: 1.7 mg/kg), with similar potencies to the inhibition of bethanechol-, neostigmine- and nicotine-induced fecal pellet output in rats (ED50: 3.3, 7.9 and 4.5 mg/kg, respectively). YM905 also inhibited 5-hydroxytryptamine (5-HT)-, prostaglandin E2- and castor oil-induced secretory diarrhea in mice (ED50: 5.5, 14 and 6.3 mg/kg, respectively), but showed no significant effect on cholera toxin-induced intestinal secretion in mice. In addition, YM905 (3, 10 mg/kg) reversed morphine-decreased postprandial defecation in ferrets, a model of spastic constipation, whereas remosetron, a 5-HT3-receptor antagonist, was not effective. The mode of YM905 action was similar to that of darifenacin, a selective M3-receptor antagonist, with equivalent potencies. By contrast, propantheline, an antimuscarinic drug that has been used for IBS, was much less potent. These results show that YM905 ameliorates a wide spectrum of bowel dysfunctions through the blockade of M3 receptors, suggesting its therapeutic potential for treating IBS.

The study aim was to develop a simple in vitro model for pharmacophysiological investigation of urinary bladder smooth muscles. Smooth muscle cells from guinea pig detrusor were dissociated, and the suspended cells were stimulated with carbachol (CCh), an acetylcholine receptor agonist. Cytosolic Ca2+ levels were determined using Fura 2 fluorescence and extracellular acidification rates were monitored by the Cytosensor microphysiometer. CCh dose-dependently increased cytosolic Ca2+ levels and extracellular acidification rates, with EC50 values of approximately 1 μM. Both the acetylcholine muscarinic receptor antagonist atropine and the M3 muscarinic receptor-preferring antagonist 4-diphenylacetoxy N-methylpiperidine (4-DAMP) inhibited the effects of CCh, three orders of magnitude more potently than the selective M2 muscarinic receptor antagonist, methoctramine. These data indicate the dominant role of M3 receptors in guinea-pig bladder but fail to show clear evidence of any functional role for M2 receptors. Since this finding agrees with a number of other studies using in vivo and in vitro models (1), cell suspensions such as these may prove to be simple tools for the pharmacological study of urinary bladder smooth muscle tissue.

Here, we investigated the anticoagulant effects of darexaban in mice and human plasma in vitro, effects of darexaban in thrombosis and bleeding models in mice, and reversal effects of anti-inhibitor coagulant complex (ACC) and recombinant factor VIIa (rFVIIa) on anticoagulant effects of darexaban. In mice, darexaban inhibited FXa activity in plasma with an ED50 value of 24.8 mg/kg. Both darexaban and warfarin prolonged prothrombin time (PT) at 3 mg/kg and 0.3 mg/kg/day, respectively. PT and activated partial thromboplastin time (aPTT) prolonged by darexaban were dose-dependently reversed by intravenously-administered rFVIIa, significantly so at 1 mg/kg. In a pulmonary thromboembolism (PE) mouse model, both darexaban and warfarin dose-dependently reduced the mortality rate, significantly so at 10 mg/kg and 3 mg/kg/day, respectively. In a FeCl3-induced venous thrombosis (VT) mouse model, darexaban (0.3-10 mg/kg) dose-dependently decreased the thrombus protein content, significantly so at doses of 3 mg/kg or higher. In a tail-transection mouse model, darexaban had no significant effect on the amount of blood loss at doses up to 10 mg/kg, while warfarin showed a dose-dependent increase in blood loss, significantly so from 1 mg/kg/day. Darexaban and its metabolite darexaban glucuronide significantly prolonged PT and aPTT in human plasma in vitro, and while rFVIIa concentration-dependently reversed the prolonged PT in this plasma, ACC dose-dependently reversed both PT and aPTT changes prolonged by darexaban. Taken together, these results suggest that darexaban has a potential to be an oral anticoagulant with a better safety profile than warfarin, and that rFVIIa and ACC may be useful as antidotes to darexaban in cases of overdose.

To help formulate a local intervention for leptospirosis in Sri Lanka, we determined the serogroups of leptospiral species among 97 patients diagnosed with leptospirosis at the University of Peradeniya Teaching Hospital, Sri Lanka. Ninety-two point eight percent of the patients were men; nearly two-thirds wereor = 35 years old; the majority had secondary or higher education level, half were farmers or laborers; and 57.7% presented in the acute-phase of the illness. Twenty-five patients (25.8%) were confirmed to have leptospirosis by a positive laboratory method; 17 and 8 cases were confirmed with a positive test by quantitative MAT and nested PCR, respectively. Of the 17 MAT positive cases, infection occurred in a variety of serogroups, but the predominant groups were Sejroe and Tarassovi. Of the 8 nested PCR positive cases, 7 were seen among those with a MAT titer200 and 1 occurred in a patient with a MAT titeror = 200 but400. Of the 8 PCR positive cases, 7 were infected with the leptospiral species L. interrogans. Approximately 26% of the clinically diagnosed patients were confirmed by the two laboratory methods. Laboratory positivity was based on the time of blood collection after the onset of fever. Further studies are warranted to refine the clinical diagnostic criteria and to develop more efficient and accurate diagnostic tests for leptospirosis in resource limited settings.

High-dose intravenous immunoglobulin (IVIG) preparations are currently used for the treatment of autoimmune diseases such as immune thrombocytopenic purpura (ITP). Although the mechanisms of IVIG efficacy remain enigmatic, some clinical and laboratory studies suggest that interaction of the Fc domain of IgG, especially the Fc domain of dimeric IgG, with its receptors (Fc gamma receptors; FcγRs) plays an essential role. In this study, IVIG was dimerized with chemical crosslinkers to augment its therapeutic efficacy. Dimerized IVIG was found to have a much higher affinity for FcγRs than monomeric IVIG. In a mouse ITP model, chemically dimerized IVIG abrogated the decrease in platelet numbers in the blood that was caused by an anti-platelet antibody at a dose that was one tenth of the required dose of IVIG. These results suggest that chemical dimerization of IVIG should greatly improve the efficacy of IVIG therapy of ITP.

Intravenous immunoglobulin (IVIG) is currently a very important therapeutic used for not only infectious diseases, but also for autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). Untoward reactions of IVIG have been thought to result from complement activation by aggregated IgG in IVIG. In addition, the aggregates have been known to activate neutrophils, which may result in the untoward reactions. However, the effect and mechanism of IVIG on neutrophils remain unclear. In this study, we investigated the activation of neutrophils by IVIG in terms of their reactive oxygen species (ROS) emission to elucidate the mechanisms. IVIG-induced ROS emission from purified neutrophils was remarkably augmented by TNF-α priming of the cells. The ROS emission from TNF-α-primed neutrophils occurred by activation with whole gammaglobulin (GG) molecules, but not F(ab')(2), Fc, or a mixture of F(ab')(2) and Fc. ROS emission by GG was inhibited by the F(ab')(2) fragment and an inhibitory antibody against FcγRIII. These results suggest that binding of IVIG to not only surface antigen(s), but also FcγRIII on neutrophils, is involved in IVIG-induced ROS emission from TNF-α-primed neutrophils, and contribute to the untoward reactions of IVIG.

Darexaban (YM150) is an oral factor Xa inhibitor developed for the prophylaxis of venous and arterial thromboembolic disease. This study was conducted to investigate the biochemical and pharmacological profiles of darexaban and its active metabolite darexaban glucuronide (YM-222714), which predominantly determines the antithrombotic effect after oral administration of darexaban. In vitro activity was evaluated by enzyme and coagulation assays, and a prothrombin activation assay using reconstituted prothrombinase or whole blood clot. In vivo effects were examined in venous thrombosis, arterio-venous (A-V) shunt thrombosis, and bleeding models in rats. Both darexaban and darexaban glucuronide competitively and selectively inhibited human factor Xa with Ki values of 0.031 and 0.020 μM, respectively. They showed anticoagulant activity in human plasma, with doubling concentrations of darexaban and darexaban glucuronide for prothrombin time of 1.2 and 0.95 μM, respectively. Anticoagulant activity was independent of antithrombin. Darexaban and darexaban glucuronide inhibited the prothrombin activation induced by prothrombinase complex or whole blood clot with similar potency to free factor Xa. In contrast, prothrombinase- and clot-induced prothrombin activation were resistant to inhibition by enoxaparin. In venous and A-V shunt thrombosis models in rats, darexaban strongly suppressed thrombus formation without affecting bleeding time, with ID₅₀ values of 0.97 and 16.7 mg/kg, respectively. Warfarin also suppressed thrombus formation in these models, but caused a marked prolongation of bleeding time at antithrombotic dose. In conclusion, darexaban is a selective and direct factor Xa inhibitor and a promising oral anticoagulant for the prophylaxis and treatment of thromboembolic diseases.

A large carcinoma ex pleomorphic adenoma (CXPA) with regional lymph node metastasis occurred in the left submandibular gland of a 64-year-old man. Initially, the patient underwent tumor extirpation and ipsilateral radical neck dissection. Histologic examination revealed the malignant component of CXPA was clear cell squamous cell carcinoma (SCC), which is quite uncommon in head and neck region. In the metastatic regional lymph nodes, aggregates of clear cells were observed. To the best of our knowledge, this is the first case of CXPA of which the malignant component is clear cell SCC. Four months after the postoperative radiotherapy, delayed regional metastasis became evident in the contralateral side of the neck. Radical neck dissection was carried out, and, microscopically, moderately differentiated SCC was identified. The patient recovered well and remained free of disease for 29 months after the second surgery.

Orthologs are genes in different species that evolved from a common ancestral gene by speciation. Currently, with the rapid growth of transcriptome data of various species, more reliable orthology information is prerequisite for further studies. However, detection of orthologs could be erroneous if pairwise distance-based methods, such as reciprocal BLAST searches, are utilized. Thus, as a sub-database of H-InvDB, an integrated database of annotated human genes (http://h-invitational.jp/), we constructed a fully curated database of evolutionary features of human genes, called 'Evola'. In the process of the ortholog detection, computational analysis based on conserved genome synteny and transcript sequence similarity was followed by manual curation by researchers examining phylogenetic trees. In total, 18 968 human genes have orthologs among 11 vertebrates (chimpanzee, mouse, cow, chicken, zebrafish, etc.), either computationally detected or manually curated orthologs. Evola provides amino acid sequence alignments and phylogenetic trees of orthologs and homologs. In 'd(N)/d(S) view', natural selection on genes can be analyzed between human and other species. In 'Locus maps', all transcript variants and their exon/intron structures can be compared among orthologous gene loci. We expect the Evola to serve as a comprehensive and reliable database to be utilized in comparative analyses for obtaining new knowledge about human genes. Evola is available at http://www.h-invitational.jp/evola/.