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Biomedical subjects

N Tsukada

Publications and source records attributed to N Tsukada.

At least 37 records · Page 2Linked to original sources
PubMed1999

The relationship between thiamine deficiency and performance of a learning task in rats.

We have been investigating the relationship between learning and thiamine. Electrical stimulation of mesencephalic periaqueductal gray matter (PAG) is known to have an aversive effect and elicits spontaneous instrumental escape behavior. We taught rats to press a lever to escape from the pain of electrical stimulation by learning to turn a switch off. Then we examined the relationship between learning and the thiamine concentration in various portions of the brain. (1) One group of rats was given a normal diet and another group was given a thiamine-deficient diet which contained half of the amount of thiamine present in the normal diet. We measured the response time required for each rat to react by moving after an electrical impulse was applied, and the running time during which the rat was moving from the starting point to the end point to press a lever. The rats that were fed the thiamine-deficient diet showed a slower response time and a longer running time than the rats fed the normal diet. (2) We divided the rats fed the normal diet into two groups, one group trained to switch off a lever and the other group not trained for such a task. We found that the thiamine concentration in the blood of the rats in the trained group was significantly higher than that in the group without training.

Animals↗
PubMed1998

Effect of pirarubicin for elderly patients with malignant lymphoma.

To determine the effect of a chemotherapy regimen containing pirarubicin, a multicenter clinical trial was performed in naive patients > or = 65 years with malignant lymphoma, between January 1990 and December 1992. The total number of patients was 37 (median age 74.2 years). One of three different types of chemotherapy regimens, which was administered every 3 to 5 weeks, was chosen for each patient at random. Regimen A (THP-COP) included pirarubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1), vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5), regimen B, modified "CHOP", included doxorubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1) vincristine (1 mg/m2; day 1) and prednisolone (30 mg/m2; days 1-5); regimen C (THP-COPE) included etoposide (80 mg/m2; day 1) in addition to regimen A. The complete response (CR) rate was 60.0%, 45.5% and 62.5% with regimen A, B and C. The partial response (PR) rate with regimen A was 20.0%, 18.2% with B and 25.0% with C. The 50% survival period with regimen A was more than 1,000 days, with C 643 days but it was only 365 days with B. The adverse effects related to these treatments occurred more frequently in regimen B than A and C showing a statistically significant difference. We concluded that chemotherapy regimens containing pirarubicin are useful and safe for the elderly patients with malignant lymphoma.

Aged↗
PubMed1998

Hematopoietic cytokine-dependent differentiation to eosinophils and neutrophils in a newly established acute promyelocytic leukemia cell line with t(15;17).

We recently established an acute promyelocytic leukemia (APL) cell line (HT93) that has the capacity to differentiate into neutrophils and eosinophils in response to all-trans retinoic acid (ATRA) and human hematopoietic cytokines. The cells had a myeloblastic morphology, were positive for surface CD33, CD34, and CD56, and showed the following karyotypes: 46, XY, t(1;12)(q25;p13), 2q+, t(4;6)(q12;q13), and t(15;17)(q22;q11). When the cells were cultured with ATRA, they showed nuclear segmentation and developed secondary granules consisting in part of neutrophils and eosinophils. In the presence of ATRA and granulocyte colony-stimulating factor (G-CSF), the cells showed polymorphonuclear neutrophil differentiation accompanied by expression of surface CD11b, CD15, CD10, positive activity for neutrophil alkaline phosphatase (NAP), and NAP mRNA expression. In cultures with ATRA and granulocyte-macrophage colony-stimulating factor (GM-CSF), IL (interleukin)-3, or IL-5, HT93 showed remarkable eosinophil maturation at day 8 as determined by luxol fast blue staining, in addition to expression of eosinophil peroxidase and major basic protein. These results indicate that HT93 is an APL cell line with the ability to differentiate into neutrophils and eosinophils, and that these lineages are dependent on the CSF added. HT 93 should prove to be a useful model in analyzing the effects of hematopoietic cytokines on proliferation, differentiation, and maturation of hematopoietic progenitors.

Alkaline Phosphatase↗
PubMed1998

Expression patterns of costimulatory molecules on cells derived from human hematological malignancies.

In order to elucidate the possibility of costimulatory molecules-mediated immuno or immuno-gene therapy for human hematological malignancies, we analyzed 30 hematopoietic cell lines and cells obtained from 48 patients with hematological malignancies for the expression of costimulatory molecules such as CD80 and CD86. The 30 hematopoietic cell lines were composed of 4 cell lines derived from the patients with T-cell acute lymphoblastic leukemia (T-ALL), 3 from Philadelphia chromosome positive ALL (Ph1+ALL), 8 from acute myeloblastic leukemia (AML), 3 from acute promyelocytic leukemia (APL), 8 from chronic myeloid leukemia at blast crisis (CML-BC), 3 from Burkitt's lymphoma and one from follicular cell lymphoma. The expression of CD80 or CD86 was frequent on cell lines derived from the patients with CML-BC or Burkitt's lymphoma, while it was rare on cell lines from T-ALL. Subsequently we analyzed the cells obtained from 48 patients with hematological malignancies, which consisted of 6 samples from patients with ALL, 30 from AML, 2 from CML-BC, 3 from B-cell lymphoma and one from each acute mixed leukemia (AMixL), adult T cell leukemia (ATL), T-cell large granular lymphocytic leukemia (T-LGL leukemia), chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS)-RAEB in T, multiple myeloma (MM) or T-cell lymphoma. Among all the 48 cases, all cases except one case with CLL and two with B cell lymphoma were demonstrated to be negative for CD80 on the neoplastic cells. CD86 and HLA-DR were shown to be expressed in 50% and 88% of total 48 cases respectively. In 30 AML samples, CD86 was positive in 15 cases (50%), which was sharply in contrast with the finding that CD80 was not detected in any AML samples. HLA-DR was expressed in 25 AML samples (83%). We also treated seven human hematopoietic cell lines with IFN-gamma, IL-12 or IL-15 and observed whether these cytokines could induce or enhance the expression of CD40, CD54, CD58 and HLA-DR as well as CD80 and CD86. The present study demonstrated that the expression of CD86 could be upregulated not only by IFN-gamma, but also by IL-12 or IL-15 in some cell lines. These findings suggested the possibility that the absence of CD80 on neoplastic cells may be associated with the lack of efficient anti-tumor immunity in most patients with hematological malignancies and that the immuno or immuno-gene therapy manipulating the expression of costimulatory molecules such as CD80 may be a useful treatment modality for hematological malignancies.

Adult↗
PubMed1997

Transplantation of CD95 ligand-expressing grafts: influence of transplantation site and difficulty in protecting allo- and xenografts.

BACKGROUND: CD95 and its ligand (CD95L) have been implicated in the regulation of immune responses. Recently, it was reported that CD95L expression prevented rejection of allogeneic grafts transplanted under the kidney capsule. In contrast, we reported that enforced CD95L expression in subcutaneously grafted cells induced acute rejection even in the syngeneic or immunodeficient hosts. In this study, we investigated whether the CD95L-expressing cells could be protected from rejection when transplanted under the kidney capsule. METHODS: CD95-negative cells (baby hamster kidney and L5178Y lymphoma cells) were transfected with CD95L cDNA to express functional CD95L. The cells were transplanted into skin or renal subcapsular space of immunocompetent or T cell-deficient nu/nu mice. RESULTS: The parental cells grew well in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. The CD95L transfectants were rejected when transplanted subcutaneously in all types of mice studied. However, when transplanted under the kidney capsule, they survived in nu/nu or syngeneic mice but were rejected in allogeneic or xenogeneic immunocompetent mice. CONCLUSIONS: These results imply that CD95L expression may not be sufficient to protect the grafts from rejection, and the survival of CD95L-bearing grafts is substantially influenced by the site of transplantation.

Animals↗
PubMed1997

Case report: haemorrhagic colitis associated with royal jelly intake.

The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea is described. Prior to the onset of symptoms the patient had taken royal jelly for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous throughout the 20 cm long sigmoid colon. Histopathologically, mucosal haemorrhage, oedema, and infiltration of inflammatory cells were observed. Transmission electron microscopic examination revealed platelet aggregation in 30% of capillaries in the mucosal lesions. The drug-induced lymphocyte stimulation test was slightly positive for royal jelly (847 c.p.m., SI = 147%) compared with the control (576 c.p.m.). The patient's signs and symptoms disappeared within a few days after the initiation of conservative therapy, and the colonic lesions disappeared after 2 weeks of this therapy. This is the first reported case of haemorrhagic colitis associated with royal jelly intake.

Colitis↗
PubMed1997

The heterogeneous expression of CD80, CD86 and other adhesion molecules on leukemia and lymphoma cells and their induction by interferon.

CD80 (B7/BB-1, B7-1) and CD86 (B70, B7-2) take an important role in the interaction between T lymphocytes and antigen presenting cells (APCs) as co-stimulatory molecules. We analyzed the manifestation of adhesion molecules, including CD80 and CD86, on some leukemia and lymphoma cells. Constitutive expression of CD80 and/or CD86 was frequently observed on B cell leukemia/lymphoma cells, while it is rare on myeloid leukemia cells. Interferon-alpha (IFN-alpha) amplified the manifestation of MHC class I and interferon-gamma (IFN-gamma) did both class I and class II. We also showed CD80 could be induced by IFN-alpha on K562 cells, which were originally negative for CD80. Our data implies the immunotherapy via CD80 and CD86 for patients with hematological malignancies and the possibility to enhance it using interferons.

Antigens, CD↗
PubMed1996

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: involvement of platelet aggregation.

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.

Adult↗
PubMed1996

Expansion of formalized in-home services for Japan's aged.

This article analyzes the social and political forces in Japan that led to the creation of the Gold Plan, a comprehensive national plan for formalized in-home services for the aged. The political strategies of the Gold Plan are examined from the following perspectives: (1) shifts from institutional to in-home services, (2) decentralization of in-home services policy, and (3) needs for expanding the number of in-home service workers. New nonprofit organizations called Resident-Participation Types (RPTs) are identified, which are self-help organizations to augment the delivery of in-home services to the aged. The current status of these new models for the aged are examined, using data from two different surveys conducted by the Japanese National Council of Social Welfare in 1992 and 1993. Finally, future issues regarding RTPs and in-home services for the aged and some policy recommendations are discussed.

Aged↗
PubMed1996

Induction therapy with all-trans retinoic acid for acute promyelocytic leukemia: a clinical study of 10 cases, including a fatal [correction of fetal] case with thromboembolism.

Ten patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Eight of 10 patients achieved complete remission (CR), and among the 8 newly diagnosed cases, 7 achieved CR. Five of 8 CR cases remained in CR after 8 to 30 months. Except for hypotension and a large gastric ulcer resulting from hyperhistaminemia, the adverse effects of ATRA were generally mild. Severe thrombotic tendency occurred in a patient treated with ATRA combined with tranexamic acid. Intensive chemotherapy consisting of daunorubicin (DNR) and other agents was scheduled for the patients who achieved CR with ATRA.

Adult↗
PubMed1996

Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY.

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.

Antigens, CD↗
PubMed1995

Thrombomodulin in the sera of patients with multiple sclerosis and human lymphotropic virus type-1-associated myelopathy.

Damage to the blood-brain barrier, which mainly consists of cerebral endothelial cells, has been demonstrated in multiple sclerosis (MS) clinically and histochemically. To investigate the endothelial cell damage, we evaluated the presence of soluble thrombomodulin in the sera of patients with MS and human T lymphotropic virus type-1-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay. Serum thrombomodulin levels were significantly increased in patients with acute relapsing MS during an exacerbation and chronic progressive MS as compared with those of controls (P < 0.001, respectively). Patients with HAM also had higher serum levels of thrombomodulin than did controls (P < 0.001). There was significant difference between patients with HAM and seropositive non-HAM carriers (P < 0.01). These results suggest that the detection of serum thrombomodulin could be used as a marker of endothelial cell damage in inflammatory diseases such as MS and HAM.

Adult↗