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Biomedical subjects

J Tsunoda

Publications and source records attributed to J Tsunoda.

At least 37 records · Page 2Linked to original sources

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Aclarubicin↗

[Prediction of survival of terminally ill cancer patients--a prospective study].

Planning effective palliative care requires accurate estimation of survival. A prospective study was performed on 150 hospice inpatients to identify prognostic factors in terminally ill cancer patients. By univariate analysis, eleven factors were found to be significantly associated with shortened survival: poor performance status, dyspnea at rest, death rattle, appetite loss, dysphagia, dry mouth, general malaise, edema, stomatitis, fever, and delirium. Multiple regression analysis showed that five factors were independent predictors of survival: performance status, dyspnea at rest, appetite loss, edema, and delirium. We discussed current problems and future directions of survival prediction for terminally ill cancer patients.

Activities of Daily Living↗

[Acute myeloid leukemia with monosomy 7 accompanied by central diabetes insipidus].

A 27-year-old female was diagnosed as having atypical aplastic anemia in 1979 because of hypercellular bone marrow with abnormal erythroblasts and megakaryocytes. Afterward the diagnosis was corrected to myelodysplastic syndrome (RA) due to the reevaluation of the bone marrow smears. In March, 1995, thirst and polyurea occurred. In April, 1995, bone marrow aspiration biopsy showed the proliferation of atypical blasts (28%), and two months later, the number of the blasts increased (30%) and leukemic progression was noticed. Only 0.5 percent of the blasts showed weak peroxidase activity, and most of the blasts had CD13, CD33 and several adhesion molecules as CD11a, CD11b, CD44, CD54 and CD56. Karyotype of the bone marrow cells was 45, XX, -7. Her polyurea was caused by central diabetes insipidus. She was also complicated by pleuritis, colon ulcer, sinusitis and hypothalamic dysfunction. The etiology of these signs was due to the leukemic cell infiltration. She died despite of receiving multi-drug chemotherapy.

Adult↗

[Double autologous peripheral blood stem cell transplantation (double APBSCT) for lymphoblastic lymphoma].

A 24-year-old male was admitted to our hospital, complaining of right back pain, in May 1995. Chest X-ray films showed an abnormal mass in the mediastinum. Computed tomography revealed massive effusion in the pleural and pericardial space. A biopsy specimen of the pleural lesion demonstrated lymphoblastic lymphoma of T cell type. After the completion of intensive chemotherapy by our original protocol, he entered into partial remission. Peripheral blood stem cells (PBSC) were harvested using a high-dose cytarabine (Ara-C) followed by granulocyte-colony stimulating factor (G-CSF) mobilization regimen. The total number of collected PBSC was enough to perform two courses of PBSCT. In January 1996, following the conditioning regimen of nimustine hydrochloride, etoposide (VP-16), Ara-C, thiotepa, he received PBSCT. Complete remission was achieved after the 1st PBSCT. In March 1996, he received the 2nd PBSCT following the conditioning regimen of carboplatin, VP-16, ifosfamide. No regimen-related toxity or delayed engrafment was observed. Subsequently, he received irradiation to his neck and mediastinum, the primary site of the disease. As of February 1997, he has no evidence of the disease.

Adult↗

The mouse Wnt-10B gene isolated from helper T cells is widely expressed and a possible oncogene in BR6 mouse mammary tumorigenesis.

From libraries made from activated mouse T lymphocytes, we have isolated cDNAs encoding Wnt-10B, a new member of the Wnt family of developmental control genes. This protein appears to be the mammalian orthologue of Wnt-10B, first identified in several non-mammalian vertebrates and recently in mouse. The mRNA expression pattern of mouse Wnt-10B indicates that it is induced following activation of helper T cells, but is also expressed in a variety of other tissues and cells of fetal or adult origin. 93 bp at the 5' end of the cDNA clone are identical to sequences previously reported as 3' flanking genomic DNA adjacent to a mouse mammary tumor virus (MMTV) provirus in the MMTV-induced BR6 mammary tumor, W26. Sequence analysis of tumor-derived genomic DNA confirms that the entire Wnt-10B gene is immediately adjacent to the provirus, suggesting that MMTV integration drives transcription of Wnt-10B, possibly contributing to the oncogenic process. Consistent with this idea is the detection of hybrid MMTV-Wnt-10B transcripts in BR6 tumor cells. T cells which produce abundant Wnt-10B mRNA were also found to produce protein.

Amino Acid Sequence↗

[Retrospective analysis on 21 patients with follicular lymphoma].

We retrospectively analyzed the clinical data of the 21 patients with follicular lymphoma admitted to our institution from 1977 to 1994. The frequency of follicular lymphoma was 9.1% in the 231 patients with non-Hodgkin's lymphoma. Overall survival rates at 1 year, 3 years, and 5 years were 90.2%, 78.2%, and 52.1%, respectively. The median follow-up of surviving patients and time to treatment failure (TTF) was 43 months and 30 months, respectively. The median time from disease progression to death was 171 days. In univariate analysis, factors associated with poor survival were stage IV (Ann Arbor staging system), anemia (hemoglobin level less than 10g/dl), bone marrow involvement, two or more extranodal sites, and failure in induction of complete remission (CR) in the entire course. Factors associated with short TTF were anemia, bone marrow involvement, and failure in induction of CR. In multivariate analysis, induction of CR affected survival and TTF independently.

Adult↗

[Treatment of 71 adult acute lymphoblastic leukemia].

From 1975 to 1989, 71 acute lymphoblastic leukemia patients aged 15 to 81 years (median 46 years) were treated at Jichi Medical School. Fifty-eight patients (81.7%) achieved complete remission (CR). Median CR duration was 219 days, and the probability of being in continuous CR at 3 years was 8.9%. Median survival was 462 days, and the probabilities of being alive at 3 and 5 years were 19.8% and 7.3%, respectively. The new regimen introduced from 1987 consisted of remission induction with L-asparaginase, daunomycin, vincristine and prednisolone, followed by intensive consolidation and maintenance. However, the treatment failed to improve outcome. The factor unfavorable for achieving early CR after first-line treatment regimen was the presence of myeloid antigen, and that for achieving final CR after second-line treatment regimen was advanced age. The factors unfavorable for remission duration were high leukocyte count and late CR. Those unfavorable for survival were advanced age and elevated blood urea nitrogen. Further improvement in the design of new protocols which include the use of several cytokines and autologous bone marrow transplantation may result in prolonged disease-free survival.

Adolescent↗

In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells: evidence for the presence of a mechanism(s) other than that involving c-kit receptor and its ligand.

The preadipose cell line, PA6, can support long-term hemopoiesis. Frequency of the hemopoietic stem cells capable of sustaining hemopoiesis in cocultures of bone marrow cells and PA6 cells for 6 wk was 1/5.3 x 10(4) bone marrow cells. In the group of dishes into which bone marrow cells had been inoculated at 2.5 x 10(4) cells/dish, 3 of 19 dishes (16%) contained stem cells capable of reconstituting erythropoiesis of WBB6F1-W/Wv mice, indicating that PA6 cells can support the proliferation of primitive hemopoietic stem cells. When the cocultures were treated with an antagonistic anti-c-kit monoclonal antibody, ACK2, only a small number of day 12 spleen colony-forming units survived; and hemopoiesis was severely reduced. However, when the cocultures were continued with antibody-free medium, hemopoiesis dramatically recovered. To examine the proliferative properties of the ACK2-resistant stem cells, we developed a colony assay system by modifying our coculture system. Sequential observations of the development of individual colonies and their disappearance demonstrated that the stem cells having higher proliferative capacity preferentially survive the ACK2 treatment. Furthermore, cells of subclones of the PA6 clone that were incapable of supporting long-term hemopoiesis expressed mRNA for the c-kit ligand. These results suggest that a mechanism(s) other than that involving c-kit receptor and its ligand plays an important role in the survival and proliferation of primitive hemopoietic stem cells.

Animals↗

Effect of synthesized constituents in the L-tryptophan product on the differentiation of eosinophils and the induction of IL-6: a possible cause of eosinophilia-myalgia syndrome.

While the pathogenesis of eosinophilia-myalgia syndrome (EMS) remains obscure, the ingestion of L-trypophan (LT) and possibly certain constituents in the LT product might be associated. We investigated the effect of chemically synthesized substances, 1,1'-ethylidene bis[tryptophan] (EBT) and its decomposition product, 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) recently identified in the implicated LT, on the eosinophil differentiation and the induction of IL-1 and IL-6. EBT and MTCA alone did not support colony formation. However, EBT or MTCA in conjunction with IL-2 induced colony-forming activity containing a small number of eosinophils. In addition, these LT constituents induced a significant level of IL-6 but not IL-1 beta in the mononuclear cells from normal volunteers and a patient with hypereosinophilic syndrome. These results suggest that certain constituents of LT product are associated with the pathogenesis of EMS through the induction of colony-stimulating factors and IL-6, hence giving rise to eosinophilia and inflammation.

Bone Marrow↗

In vivo stem cell function of interleukin-3-induced blast cells.

The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells but also into lymphoid lineage cells. The phenotypes of interleukin-3 (IL-3) induced blast colony cells were Thy-1-positive and lineage-marker-negative. We examined whether these blast colony cells contained primitive hematopoietic stem cells in vivo and could reconstitute hematopoietic tissues in lethally irradiated mice. Blast colony cells could generate macroscopic visible spleen colonies on days 8 and 12, and 5 x 10(3) blast cells were sufficient to protect them from lethally irradiation. It was shown that 6 or 8 weeks after transplantation of 5 x 10(3) blast cells, donor male cells were detected in the spleen and thymus of the female recipients but not in the bone marrow by Southern blot analysis using Y-encoded DNA probe. After 10 weeks, bone marrow cells were partially repopulated from donor cells. In a congenic mouse system, donor-derived cells (Ly5.2) were detected in the thymus and spleen 6 weeks after transplantation. Fluorescence-activated cell sorter analyses showed that B cells and macrophages developed from donor cells in the spleen. In the thymus, donor-derived cells were found in CD4, CD8 double-positive, single-positive, and double-negative populations. Reconstitution of bone marrow was delayed and myeloid and lymphoid cells were detected 10 weeks after transplantation. These results indicate that IL-3-induced blast cells contain the primitive hematopoietic stem cells capable of reconstituting hematopoietic organs in lethally irradiated mice.

Animals↗

Second relapse of acute promyelocytic leukemia (ANLL-M3) with t(15;17) and t(1;3)(p36;q21).

We describe herein a patient with acute promyelocytic leukemia (APL)-(ANLL-M3) whose bone marrow cells in the second relapse showed t(1;3)(p36;q21) together with t(15;17) (q22;q11-q12). Although a total of 21 patients with t(1;3) have been reported so far, among which three cases with de novo acute nonlymphocytic leukemia were included, our patient is the first case with APL. The hematologic findings in our case confirmed the previous observations that this anomaly is associated with relatively high platelet count and the multi-myeloid lineage involvement of leukemic cells. Our patient responded well to chemotherapy and achieved first and second remission with 42 months of total survival, contrary to our expectation that patients with this anomaly have a poor prognosis.

Chromosomes, Human, Pair 1↗

[Staphylococcus aureus sepsis in patients with hematological malignancies: increase in MRSA sepsis].

From January 1978 to August 1990, Staphylococcus aureus bacteremia (SAB) were identified in 31 patients with hematological malignancies at Jichi Medical School hospital. Mortality due to SAB was 48.4% (15/31). Of the variables analyzed, four factors were significantly associated with a poor prognosis; elderly age (p = 0.015), high granulocyte count (more than 500/microliters) (p = 0.015), presence of DIC (p = 0.011) and presence of pneumonia (p = 0.023). The incidence of methicillin-resistant SAB was 32.3% (10/31) and the first patient developed in 1985. Although not statistically significant, there was a trend of higher mortality for methicillin-resistant SAB (70%) than for methicillin-sensitive SAB (38.1%). Most strains of methicillin-resistant Staphylococcus aureus were sensitive to minocycline, chloramphenicol and vancomycin.

Adult↗

Effects of the in vivo administration of recombinant human granulocyte colony-stimulating factor following cytotoxic chemotherapy on granulocytic precursors in patients with malignant lymphoma.

We examined the effects of the in vivo administration of recombinant granulocyte colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100-800 micrograms/m2/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.

Adult↗

An exploratory factor analysis of existential suffering in Japanese terminally ill cancer patients.

To determine an underlying factorial structure of existential distress in Japanese terminally ill cancer patients, a principal components analysis was performed on 162 Japanese hospice inpatients. Existential distress commonly identified was dependency (39%), meaninglessness in present life (37%), hopelessness (37%), burden on others (34%), loss of social role functioning (29%), and feeling emotionally irrelevant (28%). By a factor analysis, three primary components accounted for 66% of the variance. 'Dependency' and 'loss of social role functioning' loaded highly on the first factor, which was interpreted as 'loss of autonomy'. 'Burden on others' and 'feeling emotionally irrelevant' loaded highly on the second component interpreted as 'lowered self-esteem', while 'hopelessness' loaded highly on the third factor. On the other hand, 'meaninglessness in present life' loaded equally on all three components, and was significantly associated with other distress. In conclusion, existential suffering of Japanese terminally ill cancer patients has three principal components: loss of autonomy, lowered self-esteem, and hopelessness. It is also suggested that meaninglessness in present life would be an underlying theme in patients' spirituality.

Adult↗