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Biomedical subjects

Takashi Asai

Publications and source records attributed to Takashi Asai.

At least 19 recordsLinked to original sources
PubMed2006

AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis.

The Notch1-RBP-Jkappa and the transcription factor Runx1 pathways have been independently shown to be indispensable for the establishment of definitive hematopoiesis. Importantly, expression of Runx1 is down-regulated in the para-aortic splanchnopleural (P-Sp) region of Notch1- and Rbpsuh-null mice. Here we demonstrate that Notch1 up-regulates Runx1 expression and that the defective hematopoietic potential of Notch1-null P-Sp cells is successfully rescued in the OP9 culture system by retroviral transfer of Runx1. We also show that Hes1, a known effector of Notch signaling, potentiates Runx1-mediated transactivation. Together with the recent findings in zebrafish, Runx1 is postulated to be a cardinal down-stream mediator of Notch signaling in hematopoietic development throughout vertebrates. Our findings also suggest that Notch signaling may modulate both expression and transcriptional activity of Runx1.

Animals↗
PubMed2006

Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies.

We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 micro g/ml, the peak alemtuzumab concentration in this patient was only 1.44 micro g/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation.

Alemtuzumab↗
PubMed2006

[Cannot intubate, cannot ventilate: airway management of difficult airways in adults].

Cannot intubate, cannot ventilate (CICV) is one major cause of death associated with general anesthesia and thus proper airway management plans are necessary. To achieve safe airway management, it is necessary first to predict if the patient's trachea can be difficult to intubate or the lungs difficult to ventilate. When difficulty is predicted, the following factors should be considered: (1) if general anesthesia is truly necessary; (2) if tracheal intubation is mandatory; (3) if muscle relaxation is required; (4) if awake intubation is safer; (5) if surgical airway is required; and (6) if tracheal intubation can prevent airway obstruction. When CICV occurred after general anesthesia, it is important to remember that the primary task is to oxygenate the patient, and not to intubate the trachea: the patient may need to be awaken, surgical airway obtained, or cardiopulmonary bypass established. To make a right decision, it is necessary to know the advantages and disadvantages of each option, as well as of each airway device, and to be acquainted with these devices during routine anesthesia. In this article, I will present six typical cases of difficult airways, and will discuss appropriate options for safer airway management.

Adolescent↗
PubMed2006

[Insertion of a laryngeal mask airway before removal of a nasotracheal tube in a patient after anterior spine surgery].

A 19-year-old man with cervical spondylosis (C4-C6) was scheduled for an anterior spine surgery. Anesthesia was induced with propofol and fentanyl, and nasotracheal intubation was performed without difficulty after vecuronium administration. Anesthesia was maintained with sevoflurane and nitrous oxide in oxygen supplemented with fentanyl. No complications were observed during the operation. After surgery, the patient's head and neck were stabilized by a halo-vest, and we attempted to minimize stress responses associated with tracheal extubation. While the patient was still deeply anesthetized, and the nasotracheal tube was in place, a laryngeal mask airway (LMA) was placed without difficulty. After confirming correct position of the LMA, the nasotracheal tube was removed without body movement or coughing. Removal of the LMA was safely performed after recovery of the patient's respiration and consciousness. We believe that the laryngeal mask airway is useful during emergence from anesthesia in the patient whose trachea is intubated nasally.

Adult↗
PubMed2005

Crk-associated substrate lymphocyte type is required for lymphocyte trafficking and marginal zone B cell maintenance.

The lymphocyte-specific Cas family protein Cas-L (Crk-associated substrate lymphocyte type) has been implicated to function in lymphocyte movement, mediated mainly by integrin signaling. However, its physiological role is poorly understood. In this study we analyzed the function of Cas-L in lymphocytes using gene-targeted mice. The mutant mice showed a deficit of marginal zone B (MZB) cells and a decrease of cell number in secondary lymphoid organs. An insufficient chemotactic response and perturbed cell adhesion were observed in Cas-L-deficient lymphocytes, suggesting that the aberrant localization was responsible for the deficit of MZB cells. Moreover, we found that lymphocyte trafficking was altered in Cas-L-deficient mice, which gave a potential reason for contraction of secondary lymphoid tissues. Thus, Cas-L affects homeostasis of MZB cells and peripheral lymphoid organs, which is considered to be relevant to impaired lymphocyte migration and adhesion.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Host-residual invariant NK T cells attenuate graft-versus-host immunity.

Invariant NK T (iNKT) cells have an invariant TCR-alpha chain and are activated in a CD1d-restricted manner. They are thought to regulate immune responses and play important roles in autoimmunity, allergy, infection, and tumor immunity. They also appear to influence immunity after hemopoietic stem cell transplantation. In this study, we examined the role of iNKT cells in graft-vs-host disease (GVHD) and graft rejection in a mouse model of MHC-mismatched bone marrow transplantation, using materials including alpha-galactosylceramide, NKT cells expanded in vitro, and Jalpha18 knockout mice that lack iNKT cells. We found that host-residual iNKT cells constitute effector cells which play a crucial role in reducing the severity of GVHD, and that this reduction is associated with a delayed increase in serum Th2 cytokine levels. Interestingly, we also found that host-residual iNKT cause a delay in engraftment and, under certain conditions, graft rejection. These results indicate that host-residual iNKT cells attenuate graft-vs-host immunity rather than host-vs-graft immunity.

Adoptive Transfer↗
PubMed2005

Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos.

The AML1/EVI1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/EVI1/+ fetal liver.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Functional domains of Runx1 are differentially required for CD4 repression, TCRbeta expression, and CD4/8 double-negative to CD4/8 double-positive transition in thymocyte development.

Runx1 (AML1) has multiple functions in thymocyte development, including CD4 repression in immature thymocytes, expression of TCRbeta, and efficient beta-selection. To determine the functional domains of Runx1 important for thymocyte development, we cultured Runx1-deficient murine fetal liver (FL) cells on OP9-Delta-like 1 murine stromal cells, which express Delta-like 1 and support thymocyte development in vitro, and introduced Runx1 or C-terminal-deletion mutants of Runx1 into the FL cells by retrovirus infection. In this system, Runx1-deficient FL cells failed to follow normal thymocyte development, whereas the introduction of Runx1 into the cells was sufficient to produce thymocyte development that was indistinguishable from that in wild-type FL cells. In contrast, Runx1 mutants that lacked the activation domain necessary for initiating gene transcription did not fully restore thymocyte differentiation, in that it neither repressed CD4 expression nor promoted the CD4/8 double-negative to CD4/8 double-positive transition. Although the C-terminal VWRPY motif-deficient mutant of Runx1, which cannot interact with the transcriptional corepressor Transducin-like enhancer of split (TLE), promoted the double-negative to double-positive transition, it did not efficiently repress CD4 expression. These results suggest that the activation domain is essential for Runx1 to establish thymocyte development and that Runx1 has both TLE-dependent and TLE-independent functions in thymocyte development.

Amino Acid Motifs↗
PubMed2005

[Evaluation of a nested-pCR to detect 18S rDNA for the diagnosis of toxoplasmic meningoencephalitis].

To detect an 18S ribosomal DNA fragment of Toxoplasma gondii Nested-PCR was used to detect an 18S ribosomal DNA fragment of Toxoplasma gondii in the CSF of 13 patients at 6 facilities in whom Toxoplasma meningoencephalitis had been suspected between January 2001 and Feburary 2005. Based on the diagnostic criteria of the CDC, all patients were treated with the anti-toxoplasmic chemotherapy based on the clinical diagnosis. Clinical improvement was observed in 11 patients, and the final diagnosis was toxoplasmosis, but the conditions of 2 patients deteriorated, and they were ultimately diagnosed with malignant lymphoma. Based on the results of the clinical diagnosis, we assessed the effectiveness of the nested-PCR method of examining the CSF for making the diagnosis of Toxoplasma meningoenephalitis. The results of the nested-PCR were positive in 8 of the 13 cases, and all 8 cases had been diagnosed with Toxoplasma encephalitis clinically. The results were negative in 5 of the 13 cases, but 3 of the 5 negative cases had been clinically diagnosed as toxoplasmosis, indicating that the test was false-negative in some cases (27.3%; 3/11). Toxoplasma meningoencephalitis is so difficult to diagnose that the development of the new, high-specificity diagnostic methods is being eagerly awaited.

Adult↗
PubMed2005

[Laryngeal mask during emergence from anesthesia in intubated patients with asthmatic attack or ischemic heart disease].

We report two patients in whom the presence of a tracheal tube induced asthmatic attack or hemodynamic instability and the laryngeal mask was useful during emergence from anesthesia. Case 1:A 24-year-old man with asthma was scheduled for reconstruction of an amputated finger. After induction of anesthesia and neuromuscular blockade, the trachea was intubated without complications. At the end of 9.5-h uneventful operation under anesthesia with sevoflurane, nitrous oxide and oxygen, inhalational anesthetics were turned off. During emergence from anesthesia, bucking with asthmatic attack occurred. Sevoflurane and theophilline resolved the attack, which recurred after termination of sevoflurane. Under deep anesthesia with sevoflurane, the laryngeal mask was placed, and then the tracheal tube removed without complications. The laryngeal mask was removed when the patient awoke uneventfully. Case 2: A 69-year-old man with a recent history of myocardial infarction was scheduled for skin grafting. After uneventful operation, sevoflurane and nitrous oxide were turned off. Multiple premature ventricular contractions (PVCs) with hypertension and tachycardia occurred, and necessitated the restart of sevoflurane. Under deep anesthesia, the laryngeal mask was inserted and the trachea extubated, and the patient regained consciousness without complications.

Adult↗