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Biomedical subjects

Takayuki Ishikawa

Publications and source records attributed to Takayuki Ishikawa.

At least 19 recordsLinked to original sources
PubMed2006

Myeloablative allogeneic hematopoietic stem cell transplantation for non-Hodgkin lymphoma: a nationwide survey in Japan.

We retrospectively surveyed the data of 233 patients who underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) for non-Hodgkin lymphoma (NHL). Donors were HLA-matched relatives in 154 patients (66%) or unrelated volunteers in 60 (26%). Ninety patients (39%) were in complete remission. One hundred ninety-three (83%) received a total body irradiation (TBI)-based regimen, and 40 (17%) received a non-TBI-based regimen. Acute graft-versus-host disease (GVHD) occurred in 155 (67%) of the 233 evaluable patients; grade II to IV in 90 (39%), and grade III to IV in 37 (16%). Treatment-related mortality (TRM) was observed in 98 patients (42%), and 68% of them were related to GVHD. In a multivariate analysis, chemoresistance, prior autograft, and chronic GVHD were identified as adverse prognostic factors for TRM. Relapse or progression of lymphoma was observed in 21%. The 2-year overall survival rates of the patients with indolent (n = 38), aggressive (n = 111), and lymphoblastic lymphoma (n = 84) were 57%, 42%, and 41%, respectively. In a multivariate analysis, chemoresistance, prior autograft, and prior radiotherapy were identified as adverse prognostic factors for overall survival. Although myeloablative allo-HSCT represents an effective therapeutic option for patients with NHL, more work is still needed to decrease TRM and relapse.

Acute Disease↗
PubMed2006

Influence of radiation dose rate and lung dose on interstitial pneumonitis after fractionated total body irradiation: acute parotitis may predict interstitial pneumonitis.

This study evaluated patients for the influence of the dose rate and lung dose of fractionated total body irradiation (TBI) in preparation for allogeneic bone marrow transplantation (BMT) on the subsequent development of interstitial pneumonitis (IP). Sixty-six patients at our institute were treated with TBI followed by BMT. All of the patients received a total TBI dose of 12 Gy given in 6 fractions over 3 days and were divided into 3 groups according to the radiation dose rate and lung dose: group A, lung dose of 8 Gy (n = 18); group B, lung dose of 12 Gy at 8 cGy/min (n = 25); and group C, lung dose of 12 Gy at 19 cGy/min (n = 23). The overall survival rate, the cumulative incidence of relapse, and the cumulative incidence of IP were evaluated in relation to various potential indicators of future IP. There were no significant differences in survival and relapse rates between patient group A and combined groups B and C. Clinically significant IP occurred in 13 patients. The cumulative incidence of IP was significantly higher in patients who developed acute parotitis as indicated by either an elevation in the serum amylase level or parotid pain of grade 1 to 2. There was no difference in IP incidence among groups A, B, and C. There was no significant difference in IP incidence between lung dose values of 8 Gy (with lung shielding) and 12 Gy (without lung shielding) and between dose rate values of 8 cGy/min and 19 cGy/ min, at least when TBI was given in 6 fractions. The presence of acute parotitis during or just after TBI may be a predictor of IP.

Adolescent↗
PubMed2006

Bone marrow transplantation with a reduced-intensity conditioning regimen in a patient with Wegener granulomatosis and therapy-related leukemia.

We describe a patient with Wegener granulomatosis (WG) who underwent long-term cyclophosphamide treatment and thereafter developed acute myelogenous leukemia (AML). After the AML was induced into remission, the patient received an allogeneic stem cell transplant (allo-SCT) from his sibling after undergoing a reduced-intensity conditioning regimen. His clinical course shortly after allo-SCT was uneventful. No clinically apparent acute or chronic graft-versus-host disease developed. Repeated analysis of the peripheral blood lymphocytes after transplantation showed complete donor chimerism. The level of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) remained undetectable until 4 months after transplantation, when it began to increase. When the level of PR3-ANCA peaked, the patient suddenly presented with fever and joint pain, which later spontaneously resolved in parallel with the declining titer of PR3-ANCA. He is now in remission for both AML and WG at 22 months after transplantation. The patient's clinical course after allo-SCT may provide us with valuable information regarding the establishment of allo-SCT as a therapeutic option for WG.

Cyclophosphamide↗
PubMed2006

Antibody responses associated with the graft-versus-leukemia effect in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATL, especially the acute and lymphoma subtypes, is poor with conventional and high-dose chemotherapy. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATL has been reported, suggesting the presence of a graft-versus-leukemia (GVL) effect against this malignancy. To identify the target antigens associated with tumor rejection, we used SEREX (serological identification of antigens by recombinant cDNA expression cloning) to screen ATL complementary DNA expression libraries with sera from an ATL patient who had a GVL response after allo-HSCT. Among the isolated clones, autocrine motility factor receptor (AMFR), which encodes a glycosylated transmembrane protein, was found to have selective reactivity with the sera obtained during tumor regression. Real-time reverse transcription polymerase chain reaction analysis for AMFR showed highest expression in the testis among normal tissues. Furthermore, aberrant AMFR expression was found in at least some ATL patients. Taken together, these findings suggest that AMFR may be one of the GVL antigens that provoke effective antitumor immunity against ATL in allogeneic settings.

Antibody Formation↗
PubMed2006

Teeth contacting habit as a contributing factor to chronic pain in patients with temporomandibular disorders.

Many different factors are known to cause and perpetuate the symptoms of temporomandibular disorders (TMD). However, the roles of parafunctional factors have not been clearly elucidated. We found one of these habits in the clinical setting. This parafunctional habit involves daily light touching of the upper and lower teeth, when the mouth is closed. We named this habit Teeth Contacting Habit (TCH). [OBJECTIVES] To investigate the following hypotheses: 1) TCH is associated with perpetuation of chronic pain of TMD patients; 2) TCH is associated with other behavioral factors. [METHODS] Two hundred and twenty-nine TMD outpatients with chronic pain were analyzed with multivariate logistic regression models. [RESULTS] TCH was found in 52.4% of patients. Patients with TCH and pain lasting for more than four months were less likely to experience improvements in pain at the first visit (OR = 1.944, p = 0.043). Other factors associated with TCH were as follows: unilateral chewing (OR = 2.802) and involvement in a precision job (OR = 2.195). [CONCLUSION] TCH can prolong TMD pain and is associated with other behavioral factors.

Adult↗
PubMed2005

Noninvasive measurement of heartbeat, respiration, snoring and body movements of a subject in bed via a pneumatic method.

We have developed a noninvasive pneumatics-based system by which to measure heartbeat, respiration, snoring, and body movements of a subject in bed. A thin, air-sealed cushion is placed under the bed mattress of the subject and the small movements attributable to human automatic vital functions are measured as changes in pressure using a pressure sensor having an almost flat frequency response from 0.1 to 5 kHz and a sensitivity of 56 mV/Pa. Using the newly developed system, heartbeat, respiration, apnea, snoring and body movements are clearly measured. In addition, the optimal signal-to-noise (S/N) ratio by which to evaluate the reliability of the heart rate measurement is presented. Heart rates were measured for four different body postures, 13 different subjects, four different bed mattresses, and three different sensor positions. For these measurements, the S/N ratios ranged from 15.9 to 23.5 dB, and so were determined to be reliable.

Beds↗
PubMed2005

Development of a new questionnaire to assess pain-related limitations of daily functions in Japanese patients with temporomandibular disorders.

BACKGROUND: Various measures/scales have been used to assess oral health-related quality of life in patients with temporomandibular disorders (TMDs). However, there have been few reports on the validity of questionnaires, and even fewer assessments of their use in Japanese sociocultural conditions. OBJECTIVES: The objectives of the study were: (i) to develop and refine the number of questions concerning pain-related limitations of daily function in the TMD questionnaire (LDF-TMDQ, 13 items) in Japanese patients with TMD, (ii) to assess factor validity, and (iii) to determine convergent and discriminant validity of the LDF-TMDQ with the observed items within a multidimensional questionnaire. METHODS: Four hundred and fifty-six (85.9%) outpatients with TMD were enrolled. The subjects were allocated into two roughly equal groups--E-group (233) for exploratory factor analysis and C-group (223) for confirmatory factor analysis [structural equation modeling (SEM)]. RESULTS: The exploratory factor analysis extracted 10 items and three factors. SEM showed the revised model to accurately describe the relationships between the measured items. As to convergent validity, the factor 'limitation in executing a certain task' and 'limitation of mouth opening' showed significant correlations with the observed items within the multi-dimensional questionnaire. However, the factor 'limitation of sleeping', show no correlation with any item. As to discriminant validity, all three factors had correlation coefficients below 0.4 with the psychological scale, the personality scale, and the visual analog scale for pain intensity. CONCLUSION: The LDF-TMDQ was reduced from 13 items to 10. The factor validity of the LDF-TMDQ, and the construct validity of 'limitation in executing a certain task' and 'limitation of mouth opening' were confirmed, while that of 'limitation of sleeping' remains to be determined.

Activities of Daily Living↗
PubMed2005

Relationship between oral sensory thresholds and depressive moods.

AIMS: The aims were to compare the sensory thresholds on the tip of the tongue with on the dorsum of the hand, and to investigate the relationship between the sensory threshold and depressive mood with volunteers whose psychological conditions were normal. METHODS: Fifty-five subjects (28 women, 27 men) took psychiatric structured diagnostic interview and Self-rating Depression Scale (SDS). In the next step, the quantitative sensory tests (light touch sensation and thermal sensory test) were carried out on the tongue and the hand. Then we investigated the relationship between depressive moods and sensory thresholds on the tongue and the hand using logistic regression model. RESULT: The sensory thresholds on the tip of the tongues were significantly different from those on the dorsum of the hands. Only on tongue tip, increment of SDS had relation to the thresholds of innoxious thermal stimulation (OR=0.152, 95% CI. 0.049-0.478) and noxious heat stimulation (OR=0.352, 95% CI. 0.169-0.734). CONCLUSION: This finding might support for the idea that depressive mood had closer association with the tongue of the orofacial areas than the dorsum of the hand.

Adolescent↗
PubMed2004

Retroviral transduction of acute myeloid leukaemia-derived dendritic cells with OX40 ligand augments their antigen presenting activity.

Recent studies have shown that human myeloid leukaemia cells can differentiate into dendritic cell (DC)-like cells (leukaemia-DCs) when cultured with a combination of cytokines. In the present study, we examined whether the transduction of leukaemia-DCs with OX40 ligand (OX40L), a member of the tumour necrosis factor (TNF) family, resulted in augmentation of their antigen presenting activity. Bicistronic retroviral vectors expressing both human OX40L and enhanced green fluorescent protein (EGFP) or EGFP alone were generated and used for transduction. Fresh leukaemic cells from five patients with acute myeloid leukaemia (AML) were isolated and retrovirally transduced with OX40L during the culture with a combination of cytokines from stem cell factor, fms-like tyrosine kinase (Flt)-3 ligand, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4) and TNF-alpha. After 7 d, the majority of cells showed DC-like morphology, and expressed higher levels of CD80, CD86 and HLA-DR than fresh leukaemic cells. The transduction efficiency was 8.5-27.2%. Leukaemia-DCs transduced with OX40L elicited higher proliferative response of allogeneic CD4+ T cells than fresh leukaemic cells, non-transduced, or mock-transduced leukaemia-DCs. Co-culture of allogeneic CD4+ T cells with OX40L-transduced leukaemia-DCs was superior in the generation of interferon (IFN)-gamma producing CD4+ T cells and in production of IFN-gamma. Furthermore, OX40L-transduced leukaemia-DCs could elicit significant proliferative response of human leucocyte antigen-matched T cells from the donor in allogeneic stem cell transplantation. These results indicate that retroviral transduction of leukaemia-DCs with OX40L augments their antigen presenting cell activity and thus renders them more suitable for tumour vaccines or ex vivo stimulation of leukaemia-specific T cells.

Acute Disease↗
PubMed2004

Primary myelofibrosis terminated in basophilic leukemia and successful allogeneic bone marrow transplantation.

Transformation of primary myelofibrosis (PMF) to basophilic leukemia is very rare. We report the case of a 44-year-old man who had had PMF for 6 years. His hematopoiesis deteriorated with marked splenomegaly, requiring multiple red blood cell and platelet transfusions. Soon after splenectomy, progressive basophilia (32.3 x 10(9)/L) developed, infiltrating the skin as well as the bone marrow. The patient underwent allogeneic bone marrow transplantation with cells from an HLA-matched sibling. Despite the presence of hyperhistaminemia (99.1 ng/mL) after conditioning with cyclophosphamide, the pregrafting and post-grafting periods were uneventful. Prophylactic administration of both H1 and H2 receptor antagonists and sufficient hydration appeared to be important.

Adult↗
PubMed2003

Apical and basolateral ATP-induced anion secretion in polarized human airway epithelia.

The present study investigated mechanisms underlying apical and basolateral P2Y(1)-mediated Cl(-) secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (I(sc)) with different properties via P2Y(1) receptors. The former comprised an immediate rise followed by a slow attenuation, whereas the latter was a transient rise with a higher peak and shorter duration (< 2 min). The actions of ATP were simulated by those of ADP, ADPbetaS, and ATPgammaS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH(3)) were without any effect on the bilateral ATP-induced I(sc), which were, in contrast, attenuated by a phosphatidylcholine-phospholipase C inhibitor (D609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Ca(2+) chelator, 1,2-bis (o-amino-phenoxy)-ethane-N,N,N',N'-tetraacetic acid tetra-(acetoxymethyl)-ester, or a Ca(2+)-activated K(+) channel inhibitor, charybdotoxin, although differential Ca(2+) signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the I(sc) and the basolateral K(+) current rather than the apical Cl(-) current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y(1) receptors couple with both phosphatidylcholine-phospholipase C and adenylate cyclase, leading to Cl(-) secretion, whose rate is essentially regulated by the Ca(2+)-activated K(+) channel-mediated K(+) conductance. This suggests the importance of this channel in airway mucociliary clearance.

Adenine↗
PubMed2003

ATP release triggered by activation of the Ca2+-activated K+ channel in human airway Calu-3 cells.

Airway mucociliary clearance is subject to the autocrine/paracrine regulation of extracellular nucleotides released from the airway epithelial cells. The present study was performed in pursuit of effective modulators of ATP release under physiologic conditions in polarized human airway epithelial cells (Calu-3). Neither isoproterenol, forskolin, nor ionomycin augmented extracellular ATP release detected by luciferase assay. However, direct activation of the human intermediate conductance, Ca(2+)-activated K(+) channel (hIK-1) by 1-ethyl-2-benzimdazolinone (1-EBIO, 1 mM) and chlorzoxazone (CZ, 1 mM) increased ATP release predominantly in the apical compartment. Measurement of fluo-3 signals revealed that 1-EBIO- and CZ-stimulated cytosolic Ca(2+) mobilization was suppressed by the presence of MRS-2179, a specific P2Y(1) receptor antagonist. The hIK-1-mediated ATP release was inhibited by a hIK-1 blocker (charybdotoxin), and an Na(+)-K(+)-2Cl(-) cotransport blocker (bumetanide) without interruption by GdCl(3), an inhibitor of stretch-activated nonselective cation (SA) channels, or glybenclamide, a blocker of the cystic fibrosis transmembrane conductance regulator (CFTR). These results suggest that a cell volume decrease via the hIK-1-mediated KCl loss and the resultant induction of a regulatory volume increase via the Na(+)-K(+)-2Cl(-) transporter may trigger release of ATP, which causes P2Y(1)-mediated Ca(2+) mobilization, through mechanisms unrelated to the CFTR and SA channels.

Adenosine Diphosphate↗
PubMed2003

Involvement of Ca2+ mobilization in tachyphylaxis to beta-adrenergic receptors in trachealis.

We examined the mechanisms underlying tachyphylaxis to beta-adrenergic receptor agonists (beta-agonists) in tracheal smooth muscle. Simultaneous measurements of isometric tension and intracellular Ca2+ concentration ([Ca2+]i) using fura-2-loaded guinea pig tracheas showed that the inhibitory effects of isoproterenol (ISO) on tension and increases in [Ca2+]i induced by methacholine exhibited marked tachyphylaxis with repeated exposure to ISO at intervals of 15 min. Similarly, the activation of single Ca2+-activated K+ (KCa) channels in on-cell patches by 1 microM ISO was gradually attenuated after repeated extracellular application of ISO to single smooth cells of porcine tracheas. Desensitization of beta-adrenergic receptor/KCa channel stimulatory coupling and relaxation responses was prevented by separately antagonizing the voltage-dependent Ca2+ channel (VDCC) with verapamil, suggesting a surprising relationship between Ca2+ influx through VDCC and beta-adrenergic desensitization. Conversely, repeated exposure of 10 U/ml protein kinase A to inside-out patches did not result in desensitization of channel activation, and repeated exposure to 10 microM forskolin modestly augmented the inhibitory effects of forskolin on tension and [Ca2+]i by methacholine, indicating that the mechanism of desensitization is mediated by the beta-adrenergic receptor/G protein complex. These results indicate that an uncoupling of beta-adrenergic receptor from KCa channels augments Ca2+ mobilization through VDCC and stimulates tachyphylaxis.

Adenylyl Cyclases↗
PubMed2003

Current status of therapeutic approaches to adult T-cell leukemia.

More than 2 decades have elapsed since the proposal of adult T-cell leukemia (ATL). Since then, the discovery of the etiologic virus, human T-cell leukemia virus type I (HTLV-I), and the establishment of the diagnostic steps of serum test and molecular study have clearly defined ATL as a distinct disease entity. Because conventional chemotherapy, which is active against other lymphoid malignancies, was proven to be ineffective for treating aggressive forms of ATL, ATL has become the target of several clinical studies for the purpose of improving therapeutic outcomes. Combination chemotherapy exclusively designed for ATL has considerably elevated the treatment response rate in ATL patients, but it has not sufficiently extended the median survival time. The introduction of antiviral agents has led to surprising effects for patients with acute ATL. Monoclonal antibodies seem to be promising, especially for patients with chemotherapy-resistant disease. Unfortunately, these approaches did not prove to be sufficient for most patients with ATL to obtain long-term survival. Recent promising reports on allogeneic stem cell transplantation (allo-SCT) for ATL have suggested that allo-SCT could overcome the limitations that other treatment modalities have not surmounted. More efforts are clearly needed to clarify the usefulness of allo-SCT, especially with reduced-intensity conditioning regimens, for ATL patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Expression of hepatitis C virus core protein associated with malignant lymphoma in transgenic mice.

Hepatitis C virus (HCV) is a major causative agent for chronic liver diseases leading to hepatocellular carcinoma (HCC) and has also been suggested to be a possible etiologic factor for different lymphoproliferative diseases, including mixed cryoglobulinemia (MC) and B-cell non-Hodgkin's lymphoma (NHL). To understand the roles of HCV core protein in the pathogenesis of HCV related diseases, we produced two lines of the transgenic mice (HC82310 and HC9053) that express the HCV core transgene. One of the lines, HC9053, developed malignant lymphoma (ML, follicular center cell type) with a high frequency (80%) at the ages over 20 months. Hepatocellular adenoma was also observed in this line of transgenic mouse. We demonstrated expression of HCV core protein and mRNA in the liver of transgenic mice, and also detected the core mRNA in the enlarged lymph nodes of the transgenic mice which developed ML. These results suggest that the core protein may play an important role in the development of ML, and that the HC9053 transgenic mice provide suitable models for understanding the mechanism of HCV-related lymphoproliferative diseases.

Animals↗