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Cholangiocarcinoma (CCA) is a rare disease characterized by malignant cells derived from the epithelial cells of the biliary duct system. Despite extensive treatments, the prognosis for CCA remains poor, emphasizing the critical need for the development of novel treatments. Considerable attention has been directed towards innate immune effector cells, which can recognize tumor cells independently of the major histocompatibility complex, laying the foundation for the development of off-the-shelf drugs. In this study, we cultured innate immune cells obtained from the peripheral blood of healthy adults and conducted a comparative analysis of the effector functions against CCA cell lines by Vδ2 γδ T cells and NK cells. This analysis was performed using standard short- and long-term cytotoxicity assays, as well as ELISA for IFN-γ. Vδ2 γδ T cells demonstrated cytotoxicity and IFN-γ production in response to CCA cells in a TCR-dependent manner, particularly in the presence of tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate, a bisphosphonate prodrug. In contrast, direct killing and antibody-dependent cellular cytotoxicity were relatively slow and weak. Conversely, NK cells displayed potent, direct cytotoxicity against CCA cells. In summary, both Vδ2 γδ T cells and NK cells show promise as innate immune effector cells for adoptive transfer therapy in the context of CCA. [ABSTRACT FROM AUTHOR]

The q-Toda equation is derived from replacing ordinary derivatives with q-derivatives in the famous Toda equation. In this paper, we associate an extension of the q-Toda equation with matrix eigenvalue problems, and then show applications of its time-discretization to computing matrix eigenvalues. With respect to the Lotka–Volterra system, we also have the similar discussion on the case of the Toda equation. [ABSTRACT FROM AUTHOR]

We previously reported that soymorphins, [mu]-opioid agonist peptides derived from soy [beta]-conglycinin [beta]-subunit, have anxiolytic-like activity. The aim of this study was to investigate the effects of soymorphins on food intake and gut motility, along with their mechanism. We found that soymorphins decreases food intake after oral administration in fasted mice. Orally administered soymorphins suppressed small intestinal transit at lower dose than that of anorexigenic activity. Suppression of food intake and small intestinal transit after oral administration of soymorphins was inhibited by naloxone or naloxonazine, antagonists of [mu]- or [[mu].sub.1]-opioid receptor, respectively, after oral but not intraperitoneal administration. The inhibitory activities of small intestinal transit by soymorphins were also inhibited by WAY100135, raclopride, or saclofen, antagonists for serotonin 5-HTIA, dopamine 02, or GABAB receptor, respectively. We then examined the order of activation of 5-[HT.sub.1A], [D.sub.2], and [GABA.sub.B] receptors, using their agonists and antagonists. The inhibitory effect of 8-hydroxy-2-dipropylaminotetralin hydrobromide, a 5-HT1A agonist, after oral administration on small intestinal transit was blocked by raclopride or saclofen. Bromocriptine, a [D.sub.2] agonistinduced small intestinal transit suppression, was inhibited by saclofen, but not by WAY100135. Baclofen, a [GABA.sub.B] agonist-induced small intestinal transit suppression, was not blocked by WAY100135 or raclopride. These results suggest that 5-[HT.sub.1A] activation elicits [D.sub.2] followed by GABAB activations in small intestinal motility. We conclude that orally administered soymorphins suppress food intake and small intestinal transit via [[mu].sub.1]-opioid receptor coupled to 5-[HT.sub.1A], [D.sub.2], and [GABA.sub.B] systems. anorexigenic activity; small intestinal motility; [[mu].sub.1]-opioid receptor; soy [beta]-conglycinin [beta]-subunit doi: 10.1152/ajpgi.00081.2010.

In this paper, we describe representations of integers by linear combinations with integer coefficients of squares of the Fibonacci numbers. Focusing on felicitous linear dependence of the Fibonacci squares, we design a numeration system with the Fibonacci squares for representing every integer uniquely. [ABSTRACT FROM AUTHOR]

Aim: Mortality rate of maintenance hemodialysis patients is known to be high. Cardio-ankle vascular index (CAVI) is an index reflecting the proper stiffness of the arterial tree from the origin of the aorta to the ankle. We aimed to clarify the utility of CAVI as a predictor of mortality in hemodialysis patients. The roles of age and nutritional conditions on survival were also examined. Methods: We followed 242 patients undergoing hemodialysis for 6 consecutive years. Data from 209 patients (mean age was 60 ± 11 years) excluding those with ankle-brachial index < 0.90 were then analyzed. CAVI and heart to ankle pulse wave velocity (haPWV) were measured using Vasera 1500. Results: Thirty-eight hemodialysis patients who died during the 6-year period had higher age, cardiothoracic ratio (CTR), CAVI, and haPWV, and lower diastolic blood pressure, albumin, phosphate, and calcium phosphate product. The Kaplanâ€"Meier curves for cumulative survival among the tertile groups showed that the mortality rate was higher in the highest tertile (T3) compared to T1/T2 for both CAVI and haPWV. Receiver operating characteristic (ROC) analysis revealed that CAVI had better discriminatory power for all-cause mortality compared to haPWV. In the Cox-proportional hazards analyses, 1 SD increase in both parameters contributed independently to all-cause mortality [CAVI: HR 1.595 (95% CI 1.108â€" 2.297), haPWV: HR 1.695 (95% CI 1.185â€" 2.425)], as well as age and CTR. Both parameters above the cut-offs estimated in the ROC analysis (CAVI ≥ 9.2, haPWV ≥ 8.9) also had independent contributions to mortality. Conclusion: Through the 6 consecutive years of follow-up in 209 HD patients, increased CAVI might represent a major modifiable risk factor for all-cause mortality. Further research is needed to examine whether CAVI-lowering interventions contribute to improved prognosis. [ABSTRACT FROM AUTHOR]

Increasing attention has been paid to human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) in the field of cancer immunotherapy. We have previously demonstrated that a novel bisphosphonate prodrug, tetrakis-pivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (PTA), efficiently expands peripheral blood Vγ2Vδ2 T cells to purities up to 95–99% in 10–11 days. In the present study, we first examined the effect of PTA on farnesyl diphosphate synthase (FDPS) using liquid chromatography mass spectrometry (LC-MS) to analyze the mechanism underlying the PTA-mediated expansion of Vγ2Vδ2 T cells. We find that the prodrug induced the accumulation of both isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), direct upstream metabolites of FDPS. This indicates that not only IPP but also DMAPP plays an important role in PTA-mediated stimulation of Vγ2Vδ2 T cells. We next analyzed TCR-independent cytotoxicity of Vγ2Vδ2 T cells. When human lung cancer cell lines were challenged by Vγ2Vδ2 T cells, no detectable cytotoxicity was observed in 40 min. The lung cancer cell lines were, however, significantly killed by Vγ2Vδ2 T cells after 4–16 h in an effector-to-target ratio-dependent manner, demonstrating that Vγ2Vδ2 T cell-based cell therapy required a large number of cells and longer time when tumor cells were not sensitized. By contrast, pulsing tumor cell lines with 10–30 nM of PTA induced significant lysis of tumor cells by Vγ2Vδ2 T cells even in 40 min. Similar levels of cytotoxicity were elicited by ZOL at concentrations of 100–300 μM, which were much higher than blood levels of ZOL after infusion (1–2 μM), suggesting that standard 4 mg infusion of ZOL was not enough to sensitize lung cancer cells in clinical settings. In addition, Vγ2Vδ2 T cells secreted interferon-γ (IFN-γ) when challenged by lung cancer cell lines pulsed with PTA in a dose-dependent manner. Taken together, PTA could be utilized for both expansion of Vγ2Vδ2 T cells ex vivo and sensitization of tumor cells in vivo in Vγ2Vδ2 T cell-based cancer immunotherapy. For use in patients, further studies on drug delivery are essential because of the hydrophobic nature of the prodrug. [ABSTRACT FROM AUTHOR]

We report a case of an anticoagulated patient with sudden onset pleural hematoma after straining at defecation to cardiac arrest on 2 weeks after lobectomy for lung cancer. We decided to perform an emergent operation for an evacuation of extrapleural hematoma immediately after resuscitation. The bleeding point was revealed on the extrapleural thoracic apex. We should be aware that extrapleural hematoma can occur because of increased intrathoracic pressure such as straining during defecation in patients on anticoagulation. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in a major histocombatibility complex (MHC) ‐unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino)ethylidene‐1,1‐bisphosphonate (PTA). PTA stimulated the expansion of Vγ2Vδ2 cells to purities up to 99%. These levels were consistently higher than those observed after expansion with zoledronic acid, the most commonly used stimulator for clinical trials. Cell numbers also averaged more than those obtained with zoledronic acid and the expanded Vγ2Vδ2 cells exhibited high cytotoxicity against tumor cells. The high purity of Vγ2Vδ2 cells expanded by PTA increased engraftment success in immunodeficient NOG mice. Even low levels of contaminating αβ T cells resulted in some mice with circulating human αβ T cells rather than Vγ2Vδ2 cells. Vγ2Vδ2 cells from engrafted NOG mice upregulated CD25 and secreted tumor necrosis factor‐α and interferon‐γ in response to PTA‐treated tumor cells. Thus, PTA expands Vγ2Vδ2 T cells to higher purity than zoledronic acid. The high purities allow the successful engraftment of immunodeficient mice without further purification and may speed up the development of allogeneic Vγ2Vδ2 T cell therapies derived from HLA‐matched normal donors for patients with poor autologous Vγ2Vδ2 T cell responses. [ABSTRACT FROM AUTHOR]

The integrable hungry Lotka-Volterra (hLV) system stands for a prey-predator model in mathematical biology. The discrete-time hLV (dhLV) system is derived from a time discretization of the hLV system. The solution to the dhLV system is known to be represented by using the Casorati determinant. In this paper, we show that if the entries of the Casorati determinant become an extended Fibonacci sequence at the initial discrete time, then those are also an extended Fibonacci sequence at any discrete time. In other words, the extended Fibonacci sequence always appears in the entries of the Casorati determinant under the time evolution of the dhLV system with suitable initial setting. We also show that one of the dhLV variables converges to the ratio of two successive extended Fibonacci numbers as the discrete time goes to infinity. [ABSTRACT FROM AUTHOR]

The Hankel determinant appears in representations of solutions to several integrable systems. An asymptotic expansion of the Hankel determinant thus plays a key role in the investigation of asymptotic analysis of such integrable systems. This paper presents an asymptotic expansion formula of a certain Casorati determinant as an extension of the Hankel case. This Casorati determinant is then shown to be associated with the solution to the discrete hungry Lotka-Volterra (dhLV) system, which is an integrable variant of the famous prey-predator model in mathematical biology. Finally, the asymptotic behavior of the dhLV system is clarified using the expansion formula for the Casorati determinant. [ABSTRACT FROM AUTHOR]

The integrable discrete hungry Lotka–Volterra (dhLV) system is easily transformed to the qd-type dhLV system, which resembles the recursion formula of the qd algorithm for computing matrix eigenvalues. Some of the qd-type dhLV variables play a role for assisting the time evolution of the others. This property does not appear in the original dhLV system. In this article, we first show the existence of a centre manifold for the qd-type dhLV system. With the help of the centre manifold theory, we next investigate the local convergence of the qd-type dhLV system, and then clarify the monotonicity related to the qd-type dhLV variables at the final phase of the convergence. [ABSTRACT FROM PUBLISHER]

The cyclic reduction method is a direct method for solving tridiagonal linear systems. At the first step of this method, a tridiagonal coefficient matrix is transformed into a pentadiagonal form. In this article, we prove that the condition number for eigenvalues of some classes of coefficient matrices always decreases after the first step of the cyclic reduction method. [ABSTRACT FROM AUTHOR]

Abstract: The anti-hypertensive peptide Arg-Ile-Tyr, which was isolated based on its inhibitory activity (IC50 =28μM) for angiotensin I-converting enzyme (ACE) from the subtilisin digest of rapeseed protein, exhibited vasorelaxing activity (EC50 =5.1μM) in an endothelium-dependent manner in the mesenteric artery of spontaneously hypertensive rats (SHRs). We named the peptide rapakinin. ACE inhibitors are reported to induce nitric oxide (NO)-dependent vasorelaxation by elevating the endogenous bradykinin level; however, the vasorelaxation induced by 10μM of rapakinin was blocked only insignificantly by HOE140 or N G-nitro-l-arginine methyl ester (l-NAME), antagonists of bradykinin B2 receptor and an inhibitor of NO synthase, respectively. On the other hand, the vasorelaxation induced by 10μM rapakinin was significantly blocked by indomethacin and CAY10441, a cyclooxygenase (COX) inhibitor and an antagonist of the IP receptor, respectively. The vasorelaxing activity of rapakinin was also blocked by lorglumide, an antagonist of the cholecystokinin (CCK) CCK1 receptor, although rapakinin has no affinity for the IP and CCK1 receptors. The vasorelaxation induced by 10μM iloprost, an IP receptor agonist, was also blocked by lorglumide, suggesting that CCK–CCK1 receptor system is activated downstream of the PGI2–IP receptor system. The anti-hypertensive activity of rapakinin after oral administration in SHRs was also blocked by CAY10441 and lorglumide. These results suggest that the anti-hypertensive activity of rapakinin might be mediated mainly by the PGI2–IP receptor, followed by CCK–CCK1 receptor-dependent vasorelaxation. [Copyright &y& Elsevier]

The discrete hungry Lotka--Volterra (dhLV) system is a generalization of the discrete Lotka--Volterra (dLV) system which stands for a prey--predator model in mathematical biology. In this paper, we show that (1) some invariants exist which are expressed by dhLV variables and are independent from the discrete time and (2) a dhLV variable converges to some positive constant or zero as the discrete time becomes sufficiently large. Some characteristic polynomial is then factorized with the help of the dhLV system. The asymptotic behaviour of the dhLV system enables us to design an algorithm for computing complex eigenvalues of a certain band matrix. [ABSTRACT FROM AUTHOR]