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Biomedical subjects

M Tsuchida

Publications and source records attributed to M Tsuchida.

At least 55 records · Page 3Linked to original sources

[Anesthetic management with veno-venous extracorporeal membrane oxygenator (VV-ECMO) in a patient with severe tracheobronchial stenosis].

We conducted an anesthetic management to perform tracheostomy and tracheolysis in a 33 year-old female with severe stenosis extending to the lower trachea and right main bronchus. The minimal diameter of the stenotic lesion of the trachea was 3 mm according to the preoperative examinations including tomography, CT scan and magnetic resonance imaging. Since there was a high risk of airway collapse during anesthetic induction that could have made ventilation impossible, we decided to apply VV-ECMO to support gas-exchange prior to anesthetic induction. Blood gas analysis showed good results, and sufficient oxygenation and stable circulation were achieved during surgical procedures. Total intravenous anesthesia with propofol and fentanyl could provide adequate depth of anesthesia during surgery and rapid recovery with good spontaneous respiration after the termination of the infusion. VV-ECMO was a useful method to support gas-exchange in a case not requiring circulatory assistance without uneven oxygenation sometimes observed in VA-ECMO.

Adult↗

T cell activation up-regulates the expression of the focal adhesion kinase Pyk2: opposing roles for the activation of protein kinase C and the increase in intracellular Ca2+.

T cell activation initiates signals that control gene expression of molecules important for T cell function. The focal adhesion kinase Pyk2 has been implicated in T cell signaling. To further analyze the involvement of Pyk2 in T cell processes, we examined the effect of T cell stimulation on the expression of Pyk2. We found that TCR ligation or PMA increased Pyk2 expression in Jurkat T cells and in normal T cells. In contrast, TCR ligation and PMA failed to induce any detectable increase in the expression of the other member of the focal adhesion kinase family, Fak, in Jurkat T cells and induced only a weak increase in Fak expression in normal T cells. The serine/threonine kinases, protein kinase C and mitogen-activated protein/extracellular signal-related kinase kinase (MEK), regulated Pyk2 expression, as inhibitors of these kinases blocked stimulus-induced Pyk2 expression. Cyclosporin A, FK506, and KN-62 did not block Pyk2 expression; thus, calcineurin and Ca2+/calmodulin-activated kinases are not critical for augmenting Pyk2 expression. TCR ligation increased Pyk2 mRNA, and the transcriptional inhibitor actinomycin D blocked Pyk2 expression. Strikingly, Ca2+ ionophores, at concentrations that in combination with other stimuli induced IL-2 expression, blocked TCR- and PMA-induced up-regulation of Pyk2 expression. Thus, the increase in Ca2+ has opposing effects on IL-2 and Pyk2 expression. Cyclosporin A and FK506, but not KN-62, blocked Ca2+ ionophore-mediated inhibition of Pyk2 expression, implicating calcineurin in down-regulating Pyk2 expression. These results show that TCR-triggered intracellular signals increase Pyk2 expression and shed light on the molecular mechanisms that regulate Pyk2 expression in T cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Activation of T lymphocytes for adhesion and cytokine expression by toxin-conjugated anti-CD3 monoclonal antibodies.

BACKGROUND: Immunosuppressive drugs that target T cells are useful for prolonging allograft survival. The anti-CD3 immunotoxin FN18-CRM9 has been shown to effectively prolong renal allograft survival in a rhesus monkey model of transplantation. However, immunotoxin-treated monkeys showed increased levels of inflammatory cytokines and produced antibodies to donor proteins. To better understand the role of FN18-CRM9 in the production of cytokines and anti-donor antibodies in the monkey model, we examined whether this immunotoxin elicits functional responses in T cells. METHODS: Purified normal rhesus monkey T cells (>98% purity) were incubated with immunotoxin FN18-CRM9 or the unconjugated anti-CD3 monoclonal antibodies and then examined for changes in protein tyrosine phosphorylation, adhesion to fibronectin, gene expression, and proliferation in the presence or absence of anti-CD28 monoclonal antibodies (mAb) and interleukin-2. RESULTS: Immunotoxin treatment of T cells in vitro increased protein tyrosine phosphorylation, cell adhesion to the extracellular matrix, and expression of the inflammatory cytokines interferon-gamma and tumor necrosis factor-alpha. These immunotoxin effects were similar in magnitude to those induced by the unconjugated mAb. In contrast, immunotoxin-induced T cell proliferation was markedly less than that induced by the unconjugated mAb. Interestingly, the mitogenic molecules IL-2 and anti-CD28 mAb did not prevent immunotoxin-induced inhibition of cell proliferation. CONCLUSIONS: The activation of T cells for protein phosphorylation, adhesion, and cytokine expression strongly suggests that the actions of FN18-CRM9 in vivo are not limited to the inhibition of protein synthesis.

Animals↗

CD28 ligation induces tyrosine phosphorylation of Pyk2 but not Fak in Jurkat T cells.

Protein tyrosine kinases are critical for the function of CD28 in T cells. We examined whether the tyrosine kinases Pyk2 and Fak (members of the focal adhesion kinase family) are involved in CD28 signaling. We found that ligating CD28 in Jurkat T cells rapidly increases the tyrosine phosphorylation of Pyk2 but not of Fak. Paxillin, a substrate for Pyk2 and Fak, was not tyrosine-phosphorylated after CD28 ligation. CD28-induced tyrosine phosphorylation of Pyk2 was markedly reduced in the absence of external Ca2+. Previous studies have shown that the T cell antigen receptor (TCR) induces tyrosine phosphorylation of Pyk2. In this report, the concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of Pyk2; however, the extent of phosphorylation by both receptors was equivalent to the sum of that induced by each receptor alone. The Syk/Zap inhibitor piceatannol blocked CD28, and TCR induced tyrosine phosphorylation of Pyk2, suggesting that Syk/Zap is involved in Pyk2 phosphorylation. In contrast, the phosphatidylinositol 3-kinase inhibitor wortmannin blocked TCR- but not CD28-induced phosphorylation of Pyk2, suggesting that CD28 and TCR activate distinct pathways to induce tyrosine phosphorylation of Pyk2. Notably, depleting phorbol 12-myristate 13-acetate-sensitive protein kinase C did not block CD28- and CD3-induced tyrosine phosphorylation of Pyk2. These data provide evidence for the involvement of Pyk2 in the CD28 signaling cascade and suggest that neither Fak nor paxillin is involved in the signaling pathways of CD28.

CD28 Antigens↗

Persistence and clinical outcome of hepatitis G virus infection in pediatric bone marrow transplant recipients and children treated for hematological malignancy.

The natural course and the clinical significance of hepatitis G virus (HGV) infection were investigated in 106 pediatric patients who received chemotherapy for hematological malignancy or underwent bone marrow transplantation (BMT) using HGV-RNA and antibodies to the HGV-E2 protein (anti-E2). HGV markers were detected in 21 patients (19.8%; HGV-RNA in 19 and anti-E2 in 2). Longitudinal analysis of these HGV-infected patients showed that 1 had anti-E2 before the initial blood transfusion, 14 had persistent viremia, and 6 became clear of circulating HGV-RNA after completion of therapy, although 5 of the 6 HGV-cleared patients never developed anti-E2. Reactivation of HGV infection during chemotherapy was observed in two anti-E2-positive, HGV-RNA-negative patients; the reappearance of the same HGV strain was confirmed by phylogenetic analysis. Among BMT survivors without other known causes of liver dysfunction, HGV-RNA-positive patients had a higher peak serum alanine amino transferase (ALT) value than negative patients. Contrary to previous reports, immunosuppressed patients can apparently recover from HGV infection without detectable anti-E2 and some patients who supposedly recovered from HGV infection can nonetheless suffer exacerbation when subsequently immunosuppressed.

Adolescent↗

CD28 ligation induces rapid tyrosine phosphorylation of the linker molecule LAT in the absence of Syk and ZAP-70 tyrosine phosphorylation.

CD28 is a T cell surface molecule that is important for T cell activation. CD28-triggered T cell stimulation involves protein tyrosine phosphorylation, a process that is critical for CD28 function. Recently, a linker molecule has been identified as LAT (Linker for Activation of T cells). Studies involving LAT mutants and reconstitution experiments strongly implicate LAT in playing a critical role in T cell activation. We show in the present report that CD28 ligation induces tyrosine phosphorylation of LAT. CD28-induced tyrosine phosphorylation of LAT was rapid, as it was apparent within 1 min of CD28 ligation, reached a peak by 5 min, and declined thereafter. Previous studies implicated the protein tyrosine kinases ZAP-70 and Syk in the TCR-induced tyrosine phosphorylation of LAT. Here, tyrosine phosphorylation of Syk and ZAP-70 was detected after TCR but not after CD28 ligation. Thus, CD28 ligation appears to induce tyrosine phosphorylation of LAT by mechanisms that are independent of ZAP-70 and Syk. The concurrent ligation of CD28 and TCR increased tyrosine phosphorylation of LAT. These results implicate LAT in CD28 signal transduction pathways and in the co-stimulatory process in T cells.

Adaptor Proteins, Signal Transducing↗

A magnetic resonance abnormality correlating with permeability of the blood-brain barrier in a child with chemical meningitis during central nervous system prophylaxis for acute leukemia.

Chemical meningitis developed in a boy with acute lymphoblastic leukemia during central nervous system (CNS) prophylaxis. Cerebrospinal fluid examination showed pleocytosis and a high protein level. There were no malignant cytological findings. Calculated permeability of albumin across the blood-brain barrier (BBB) was more elevated than that of immunoglobulin or alfa2-macroglobulin. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement without any intracerebral lesion. Subsequent CNS prophylaxis was postponed. CSF findings and BBB permeability returned to normal, correlating well with the decrease of MRI abnormality.

Albumins↗

Efficacy and safety of extended thymectomy for elderly patients with myasthenia gravis.

BACKGROUND: The number of elderly patients who are diagnosed as myasthenia gravis (MG) is increasing in Japan. Although several factors affecting thymectomy have been well documented, few studies have focused on the efficacy and safety of thymectomy for elderly patients older than 60 years. METHODS: We evaluated 94 patients with MG who underwent extended thymectomy, and divided them into two groups: patients younger than 59 years and patients older than 60 years. Preoperative patient data, pathology of the thymus, complications, and clinical outcome were evaluated. RESULTS: In 69 young patients and 25 elderly patients, we observed no significant differences between the two groups with regard to preoperative data. Thymic hyperplasia was present in 45% of the young group and 16% of the elderly group. Remission and improvement rate were 40% and 57% in the young group and 8% and 75% in the elderly group, respectively. There were no serious complications, except one early death due to gastrointestinal bleeding in the elderly group. CONCLUSIONS: We conclude that thymectomy is a safe and effective alternative for elderly patients with MG.

Adolescent↗

Successful tracheal transplantation using cryopreserved allografts in a rat model.

OBJECTIVES: The purpose of this study was to determine the appropriate cryopreservation period of tracheal allografts based on morphological and immunological findings and to test the possibility of tracheal transplantation in rats using cryopreserved allografts without immunosuppression. METHODS: Morphological and immunological studies were performed to compare the differences between non-cryopreserved grafts and cryopreserved grafts. Orthotopic tracheal transplantation using cryopreserved allografts, non-cryopreserved allografts, and non-cryopreserved autografts was performed and the rejection score of each group was evaluated. RESULTS: Epithelial cells were lost when the grafts were cryopreserved for more than 20 days. Immunohistochemical staining of the trachea revealed that the MHC classII antigen was expressed on normal epithelium. These findings suggest that cryopreservation for more than 20 days decreased the antigeneicity of allografts because of epithelial desquamation. All rats that received allografts cryopreserved for more than 20 days survived until the scheduled sacrifice day. Microscopically, cryopreserved allografts that had been preserved for more than 20 days had a significantly lower rejection score than that of non-cryopreserved allografts (P < 0.05). CONCLUSIONS: We conclude that the appropriate period for cryopreservation of allografts would be 20 days or more, because cryopreservation for more than 20 days depleted epithelium, which possessed the MHC classII antigen. Therefore, a longer period of cryopreservation decreases the antigeneicity of allografts. Rat tracheal transplantations using cryopreserved allografts is possible without immunosuppression when the grafts have been cryopreserved for more than 20 days.

Animals↗

Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia.

In December 1991, the Japan Marrow Donor Program (JMDP) was established with the cooperation of the Japanese Red Cross and Japan Marrow Donor Foundation under the auspices of the Ministry of Health and Welfare in Japan. By December 1998, 122365 HLA-A,B typed volunteer marrow donors and 7207 patients had been cumulatively registered in the JMDP. The results of HLA-matching between donors and patients revealed that 5684 out of 7207 (78.9%) patients could have at least one HLA-A,B,DR serologically matched donor. Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.

Acute Disease↗

CT-guided agar marking for localization of nonpalpable peripheral pulmonary lesions.

BACKGROUND: Small pulmonary lesions with ground-glass opacity (GGO) are increasingly detected by CT; however, intraoperative localization of such lesions is difficult because these lesions are often invisible and nonpalpable. STUDY OBJECTIVES: To localize and resect nonpalpable and invisible small pulmonary lesions, a new marking technique that we call "agar marking" was developed. METHODS AND PATIENTS: Powdered agar was dissolved in distilled water at a concentration of 5% and kept at > 50 degrees C to maintain its liquid form. Agar was injected through an 18-gauge needle and placed near the target lesion with CT. After animal experiments, agar marking was applied to the nine patients who had lesions < 20 mm in diameter and lesions with GGO. The mean diameter of these lesions was 11 mm, with a mean depth of 19 mm from the pleural surface on CT. RESULTS: Agar could be detected as a hard nodule by manual palpation, and the lesion was resected during thoracotomy in all cases. There were no complications associated with the agar injection, aside from one case of slight pneumothorax. CONCLUSIONS: Agar marking may represent a feasible alternative technique for localizing nonpalpable occult lesions located away from the pleural surface.

Agar↗

[Infant leukemia with t(1;22) presenting proliferation of erythroid and megakaryocytic cell lineages].

We report a case of infant leukemia with the proliferation of both erythroblast and megakaryoblast lineages. The blasts became double-positive for both erythroblastic and megakaryoblastic surface markers at the time of bone marrow relapse. A 9-month-old girl was admitted to our hospital presenting chiefly poor with weight gain and anemia. She also had splenomegaly, pleural effusion, leukocytosis, and thrombocytopenia. A bone marrow specimen showed 53.2% erythroblasts (PAS positive, alpha-NA positive, CD41 negative, MPO negative) and 20.4% megakaryoblasts with marked cytoplasmic blebs. We examined specimens by two-color flow cytometric analysis. At the onset, CD41+ glycophorin A- fraction and CD41- glycophorin A+ fraction were two major components. At the bone marrow relapse, the majority of blasts had altered to double-positive. Chromosomal analysis showed t (1; 22) (p13; q13), which has been reported to be specific for acute megakaryoblastic leukemia (M7) in infants. We reasoned that a leukemia had occurred in this patient at a progenitor cell level common to both erythroid and megakaryocytic lineages.

Bone Marrow Cells↗

[A case of thoracoscopic resection of a pulmonary infarction mimicking a metastatic lung tumor].

We report here a rare case of pulmonary infarction which was resected as a metastatic pulmonary tumor. A 57-year-old male patient referred for exhibiting an abnormal shadow on chest X-ray 8 months after the resection of invasive adrenal tumor. The patient underwent thoracoscopic resection of the lesion as a metastatic tumor. However, intraoperative pathological examination revealed that the resected specimen was pulmonary infarction. Post-operative MRI and ultrasound images showed no evidence of venous thrombus. Pulmonary infarction can exhibit an abnormal shadow in the lung fields, and it is necessary to be distinguished from true tumor.

Diagnosis, Differential↗

Clinical and biological aspects of acute lymphoblastic leukemia in 62 infants: retrospective analysis of the Tokyo Children's Cancer Study Group.

BACKGROUND: As a first step to formulate a new treatment strategy for refractory acute lymphoblastic leukemia (ALL) in infants, clinical results and immunophenotypic and cytogenetic data were analyzed and compared with those from overseas. METHODS: There were 62 infants with ALL who were treated between 1977 and 1995 at 30 institutions affiliated with the Tokyo Children's Cancer Study Group. Clinical and laboratory data obtained from these infants (all under 1 year of age) were retrospectively studied. RESULTS: The morphological diagnoses were FAB-L1 for 51 patients (82.2%) and FAB-L2 for 11 patients (17.8%). Hepatomegaly and splenomegaly were found in 40 (70.0%) and 40 patients (68.3%), respectively. The mean (+/- SEM) leukocyte count at diagnosis was 205,900 +/- 35,700/microL. The involvement of the central nervous system was evident in nine of 36 patients who were subjected to lumbar puncture, while three of these nine patients were free of neurological symptoms at diagnosis. Thirty-one patients (55.4%) were CD10 negative and 14 (25.0%) were CD10 positive. Thirty-one of 47 patients (65.9%) exhibited chromosomal abnormalities, including 28 patients (59.6%) with 11q23 abnormalities. Rearrangements in the MLL gene were found in nine of 13 infants (69.2%) examined. Translocation of 11q23 and/or MLL gene rearrangement (11q23/MLL) was significantly associated with the absence of the CD10 antigen. Hyperleukocytosis of more than 50,000/microL and 11q23/MLL gene rearrangements were related to a poor prognosis. The probability of an event-free survival in 62 infants was 13.1 +/- 4.8% at 48 months. CONCLUSIONS: New therapeutic strategies and large-scale cooperative prospective trials are needed to improve the prognosis of ALL in infants.

Chromosomes, Human, Pair 11↗

Clinical application of a fiberscope for periodontal lesions: case reports.

In dentistry, the endoscope has generally been used to visualize inaccessible areas, e.g., inside root canals or coronal surfaces of teeth; however, it has not been used in periodontally diseased lesions. In this study, a newly designed fine fiberscope (0.8- to 1.0-mm outer diameter) with an irrigation system was used to visualize root surfaces and periodontal tissues affected by periodontal disease. The fiberscope was inserted through fistulas, periodontal pockets, or root furcations in 5 patients to provide clear operational views without the obstruction of blood or soft tissues. The irrigation system of the endoscope effectively allowed differentiation of hard and soft tissues as well as restorative materials. The fiberscope system developed in this study was effective for diagnosis, for enhancing visualization for periodontal surgery, and for treating lesions such as fistulous tracts or furcation lesions.

Adult↗

Safety evaluation of Nostoc flagelliforme (nostocales, Cyanophyceae) as a potential food.

The safety of the alga genus Nostoc flagelliforme Born. etFlah. as a human food source was evaluated in an oral acute toxicity study and in a 28-day oral subacute toxicity study using rats. In the acute toxicity study, the dried powder of N. flagelliforme was orally administered to male and female rats at a dose of 1250 mg/kg and 2500 mg/kg. Neither mortality nor changes in general condition were observed in either the study groups or the control group over a 14-day observation period. In the subacute toxicity study, N. flagelliforme powder was administered orally to male and female rats at a dose of 500 mg/kg and 1000 mg/kg for a period of 28 days. Neither mortality nor changes in general condition were observed in either the treatment group or the control group throughout the 28-day administration period. No reduction in food consumption or body weight gain was observed in the experimental animals. Ophthalmological tests performed at the end of the administration period revealed no abnormalities within the ophthalmological parameters. In the haematological tests and serum biochemical tests performed at the time of completion of the administration period, no adverse effects of N. flagelliforme were observed. At autopsy, organ weight at the end of the experimental period and histopathological tests of specimens obtained from the autopsied animals revealed no significant influences of N. flagelliforme. In conclusion, considering the absence of adverse effects of N. flagelliforme in this study, findings in the oral acute toxicity study and the 28-day oral subacute toxicity study may indicate the safety of N. flagelliforme for human consumption. This study is in agreement with the novel nutraceutical idea "Phycophagism".

Animals↗