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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 307 records · Page 17Linked to original sources
PubMed1992

All-trans-retinoic acid induced enrichment of functionally normal neutrophils in vivo in a patient with acute promyelocytic leukemia.

A patient with resistant acute promyelocytic leukemia was treated with all-trans-retinoic acid (45 mg/m2 per day for 42 days) and obtained complete remission at day 14. Analysis of the neutrophils from the patient at day 7 demonstrated that they were indistinguishable from neutrophils from normal individuals as far as this is assessed by presently available functional tests. Furthermore, the degree of peroxidase positivity of neutrophils obtained from the patient was similar to control values. Thus, taken together with the hematologic features, all-trans-retinoic acid induces leukemic promyelocytes to become functionally normal neutrophils. This therapy is particularly suitable in obtaining complete remission in patients with acute promyelocytic leukemia with neutropenia with or without previous chemotherapy.

Female↗
PubMed1991

Methylation status of T-cell receptor beta-chain gene in B precursor acute lymphoblastic leukemia: correlation with hypomethylation and gene rearrangement.

Epigenetic changes may play a role in genetic alterations in cancer cells, but little is known about this phenomenon. In this study we examined the correlation between rearrangement and methylation status of the T-cell receptor (TCR) beta-chain gene in 23 patients with B precursor acute lymphoblastic leukemia (ALL). In B precursor ALL, all patients had a CCmeGG sequence in the C beta 2 region, a pattern similar to that observed in normal mature B-cells. Approximately 55% of patients with B precursor ALL exhibiting a hypomethylated CCGG sequence at the J beta 1 region showed rearrangement of this region. Furthermore, the same allele of rearranged J beta 1 always contained an unmethylated sequence in the region, although another allele without rearrangement contained methylated J beta 1. By contrast, none of the patients had a rearrangement in the J beta 1 region without hypomethylation. Therefore, rearrangement of the J beta 1 region may link to the hypomethylation status of this region. A close association between hypomethylation of the J beta 1 region may promote accessibility to a putative common recombinase to produce TCR J beta 1 rearrangement. In contrast, about 45% of patients with a hypomethylated J beta 1 did not show rearrangement in this region, thus allowing categorization of B precursor ALL patients into subtypes, according to the combination of TCR beta-chain gene rearrangement and hypomethylation status, especially in the J beta 1 region.

Burkitt Lymphoma↗
PubMed1991

Acute lymphoblastic leukemia with azurophilic granules that contain ultrastructural myeloperoxidase activity.

We present a case of acute lymphoblastic leukemia (ALL) in which the leukemic cells had cytoplasmic azurophilic granules. Surface marker studies revealed that the leukemic cells expressed CD10 (CALLA), CD19, CD20, and HLA-DR antigens. Cytochemical studies by light microscopy revealed that the blasts were negative for myeloperoxidase, PAS staining, and double esterase staining, supporting the diagnosis of ALL. However, an ultrastructural study demonstrated that some of the cytoplasmic granules were myeloperoxidase (MPO) positive. Our findings suggested that leukemic transformation in this case may have taken place at a stage ontogenetically close to the pluripotent stem cell. Furthermore, the present case indicates the existence of a new form of ALL is characterized by MPO-positive granules detectable by ultracytochemistry and lymphoid-associated surface markers.

Antigens, CD19↗
PubMed1991

Establishment of a new Epstein-Barr virus nuclear antigen-positive B-cell line, BALL-2, with t(8;14) (q24;q32) chromosome abnormality from B-cell acute lymphoblastic leukemia, L2.

A new Epstein-Barr virus nuclear antigen (EBNA)-positive B-cell line, designated BALL-2, was spontaneously established from the peripheral blood of a 14-year-old boy with an EBNA-negative B-cell acute lymphoblastic leukemia (B-ALL), L2 in the French-American-British classification. The BALL-2 cell line grew in suspension with or without forming clumps of cells. The cultured cells exhibited lymphoid morphology with indented or lobulated nuclei, prominent nucleoli, and relatively abundant cytoplasm. Immunologic and cytogenetic studies showed that the BALL-2 cell line expressed the B-cell phenotype, CpIg+, SmIg+, CD19+, CD20+, CD38-, Ia+, and had chromosome translocation, t(8;14) (q24;q32). The same phenotypic and chromosome markers were present in original leukemia cells. These results indicated that the cell line was derived from the patient's leukemia cells. Unexpectedly, however, BALL-2 cells were positive for EBNA and EB virus DNA. Gene analysis of the BALL-2 cell line showed biallelic rearrangements in the JH locus. One of the JH rearrangement comigrated with a rearranged c-myc gene, indicating the translocation had occurred between JH and c-myc loci. The t(8;14) abnormality is a known chromosome marker of Burkitt lymphoma and L3 type ALL. Our studies revealed that this translocation and myc gene rearrangement can also be found in L2 type B-ALL.

Adolescent↗
PubMed1991

Establishment of a variety of human bone marrow stromal cell lines by the recombinant SV40-adenovirus vector.

Various human bone marrow stromal cell lines were established from the adherent cell populations by introduction of the recombinant SV40-adenovirus vector with an infection or electric poration procedure. As compared with DNA transfection, the vector introduction was able to immortalize the cells with more than 100 times higher efficiency. Morphological and cytochemical analyses indicated that various cloned cell lines with different properties were isolated by the vector introduction. All the established cell lines expressed SV40 large T antigen. These results provided the evidence indicating that the recombinant SV40-adenovirus vector was a useful tool to establish a variety of cell lines with different biological activities from human bone marrow stroma.

Adenoviridae↗
PubMed1991

Binocular neuronal responsiveness in Clare-Bishop cortex of Siamese cats.

Retinotopy and binocular responsiveness were studied extracellularly in a total of 278, 61, 110 and 275 cells sampled in areas 17, 18, 19 and Clare-Bishop (CB) of Siamese cats. The misalignment of the visual axes of the two eyes was determined by the pupil reflex method in the behaving animal. The recording sessions were conducted under N2O anesthesia, supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo) and muscle relaxants (Gallamine triethiodide) using two types of visual stimulators presenting two-dimensional (2D) motion stimuli and the visual cues for three-dimensional (3D) motion. All of the nine Siamese cats demonstrated Boston type retinotopic abnormalities in all of cortical areas 17-19 and CB. Very few binocular cells were present in areas 17-19 and the posterior (A1-P2) CB but they were numerous in most of CB (A9-4). A significant fraction (36/78) of binocular cells in the major CB of the Siamese cats demonstrated similar response selectivity to that reported in normal CB cortex for stimulation with the 3D motion cues under both null disparity and strabismic conditions (binocular receptive fields for two eyes were optically superposed or separated by the strabismic angles estimated in the individual animals). These findings indicate that the binocular signals converging to the CB cells through different pathways (signals coming from the contralateral eye via the ipsilateral hemisphere including the interlaminar nucleus and areas 17-19, and commissural signals from the ipsilateral eye via the contralateral areas 17-19 and CB) were integrated to yield useful information for the recognition of 3D motion, and that the major CB is an actual site of binocular integration at least in Siamese cats, rather than being merely a reflection of the information processing before the CB cortex.

Anesthesia↗
PubMed1991

Superoxide anion production and expression of cytochrome b 558 by neutrophils are impaired in some patients with myelodysplastic syndrome.

Superoxide anion (O2-) production and expression of cytochrome b 558 by neutrophils were determined in 20 patients with myelodysplastic syndrome (MDS). The reduction of O2- production was noted in eight of the 20 patients and an increase was noted in four patients when neutrophils were stimulated by n-formyl-methionyl-leucyl-phenylalanine (FMLP), while a low level of O2- production was found in 11 and an increase in six MDS patients when they were stimulated by phorbol myristate acetate (PMA). Among them, seven patients showed a decrease and four an increase in O2- production on stimulation with either FMLP or PMA. Expression of cytochrome b 558 was found to be at low levels in patients who had neutrophils showing decreased O2- production when stimulated with FMLP, indicating that decreased expression of cytochrome b 558 might contribute to the impairment of O2- production in some MDS patients. In this study, no significant differences in O2- production were noted among subtypes of MDS; however, the patients who had received prednisolone showed lower levels of O2- production than those who had not received prednisolone. Patients manifesting episodes of infection had reduced levels of O2- production compared with those without infection. Furthermore, the fact that one patient who exhibited a marked reduction in neutrophil counts together with reduced O2- production died of fatal infection, suggests that the determination of O2- production, in combination with hematological features, may be of some help in predicting severe infection.

Adult↗
PubMed1991

In vitro approach to visual cortical development and plasticity.

The neural circuitry in the visual cortex is characterized by two basic types of organization. One is a laminar organization determining the extrinsic and intrinsic neural connections of cortical cells according to their cortical depth, and the other is a columnar organization where cortical cells are arranged perpendicularly according to their response selectivities. It is known that the columnar organization comprises the postnatal structures dependent on the visual experience, while the laminar organization comprises the prenatal structures unmodified by visual experience. We have investigated the interplay between the pre- and postnatal mechanisms using various in vitro preparations, including visual cortical slices, and transplant and co-culture preparations. It was shown in lateral geniculate and visual cortex transplants and co-cultures including the visual cortex lateral geniculate nucleus that all laminar structures are expressed in these preparations according to the prenatal mechanisms. It was also shown in slice preparations that the details of these circuitries are plastic and modifiable by the visual input, although their basic framework is determined prenatally.

Aging↗
PubMed1991

Microbial sensor system for nondestructive evaluation of fish meat quality.

A microbial sensor system consisting of the bacterium (Alteromonas putrefaciens) immobilized within membranes, a flow cell, an oxygen electrode, peristaltic pumps, a buffer tank, a thermostatically controlled bath and a recorder, was constructed for the nondestructive quality evaluation of bluefin tuna. The chemical compounds on fish meat surfaces which are the indicators of fish meat quality were rapidly determined by using the proposed sensor system. Fish meat quality was determined from the rate of current decrease of the sensor. Good correlations were obtained between fish meat quality and sensor response. One assay could be completed within one minute.

Animals↗
PubMed1991

Induction of long-term potentiation without participation of N-methyl-D-aspartate receptors in kitten visual cortex.

1. Intracellular recording was made from layer II-III cells in slice preparations of kitten (30-40 days old) visual cortex. Low-frequency (0.1 Hz) stimulation of white matter (WM) usually evoked an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). The postsynaptic potentials (PSPs) showed strong dependence on stimulus frequency. Early component of EPSP and IPSP evoked by weak stimulation both decreased monotonically at frequencies greater than 0.5-1 Hz. Strong stimulation similarly depressed the early EPSP at higher frequencies (greater than 2 Hz) and replaced the IPSP with a late EPSP, which had a maximum amplitude in the stimulus frequency range of 2-5 Hz. 2. Very weak WM stimulation sometimes evoked EPSPs in isolation from IPSPs. The falling phase of the EPSP revealed voltage dependence characteristic to the responses mediated by N-methyl-D-aspartate (NMDA) receptors and was depressed by application of an NMDA antagonist DL-2-amino-5-phosphonovalerate (APV), whereas the rising phase of the EPSP was insensitive to APV. 3. The early EPSPs followed by IPSPs were insensitive to APV but were replaced with a slow depolarizing potential by application of a non-NMDA antagonist 6,7-dinitro-quinoxaline-2,3-dione (DNQX), indicating that the early EPSP is mediated by non-NMDA receptors. The slow depolarization was mediated by NMDA receptors because it was depressed by membrane hyperpolarization or addition of APV. 4. The late EPSP evoked by higher-frequency stimulation was abolished by APV, indicating that it is mediated by NMDA receptors, which are located either on the recorded cell or on presynaptic cells to the recorded cells. 5. Long-term potentiation (LTP) of EPSPs was examined in cells perfused with solutions containing 1 microM bicuculline methiodide (BIM), a gamma-aminobutyric acid (GABA) antagonist. WM was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes were tested by low-frequency (0.1 Hz) stimulation of WM. 6. LTP of early EPSPs occurred in more than one-half of the cells (8/13) after strong conditioning stimulation. The rising slope of the EPSP was increased 1.6 times on average. 7. To test involvement of NMDA receptors in the induction of LTP in the early EPSP, the effect of conditioning stimulation was studied in a solution containing 100 microM APV, which was sufficient to block completely synaptic transmission mediated by NMDA receptors. LTP occurred in the same frequency and magnitude as in control solution.

2-Amino-5-phosphonovalerate↗
PubMed1991

Treatment of myelodysplastic syndromes with orally administered 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate.

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS.

Adult↗
PubMed1991

Interleukin-4 as a growth regulator of clonogenic cells in acute myelogenous leukemia in suspension culture.

Using two complementary culture systems, suspension and clonal cultures, and with a method of graphic display (star diagram), we studied the effects of recombinant human interleukin-4 (IL-4) on leukemic stem cell renewal and differentiation in acute myelogenous leukemia (AML). The interactions between IL-4 and other recombinant human cytokines, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), macrophage CSF (M-CSF) and interleukins-1 alpha, -2, -3, -5, and -6 were also studied. IL-4 alone had significant effects on both self-renewal and differentiation of blast progenitors in some cases; in clonogenic assay, IL-4 stimulated blast colony formation and in one case IL-4 was the most powerful stimulator among the nine growth factors tested. Star diagrams, constructed using the data from both suspension and clonal cultures, showed that IL-4 could influence the balance between self-renewal and differentiation of clonogenic cells. Negative and positive interactions were detected between IL-4 and other cytokines in suspension culture. These results indicate that IL-4 is a cytokine with a potential role in regulating the growth of myeloid leukemic stem cells, and that IL-4 may be useful in treating selected AML patients.

Adult↗
PubMed1991

In vivo effects of recombinant human granulocyte colony-stimulating factor on normal neutrophil function and membrane effector molecule expression.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now undergoing clinical trials. We investigated the effects of rhG-CSF on the function of neutrophils in vivo in healthy volunteers. rhG-CSF (0.5 micrograms/kg) was injected subcutaneously for 6 consecutive days. The number of neutrophils in peripheral blood decreased transiently within an hour, and thereafter increased 2-10-fold compared to the control 6 to 8 h after injection. The circulating neutrophils remaining during this early neutropenic period showed increases in such functions as random motility, chemotaxis, phagocytosis and superoxide anion production. On the other hand, the function of neutrophils which increased 6 to 8 h after rhG-CSF injection was normal. No decrease of neutrophil function was observed following the use of rhG-CSF. CD33-positive cells increased 3 days after rhG-CSF administration. CD11a (LFA-1) expression on the membranes circulating neutrophils decreased 6 h after rhG-CSF administration. This phenomenon suggested that neutrophils adhered to the reticuloendothelial system during neutropenia, and that there was an influx of CD11a-negative mature cells into the circulatory pool thereafter. All our findings suggest that rhG-CSF enhances the function of normal neutrophils in vivo, and that it is effective against microbial infection very soon after administration.

Adult↗
PubMed1991

Flow cytometric DNA analysis of poorly differentiated adenocarcinoma of the colorectum.

DNA ploidy patterns in 11 poorly differentiated adenocarcinomas of the colorectum were examined by flow cytometry using paraffin-embedded specimens. Measurements of DNA content were made of the superficial (Sup) half and deeper (Deep) half of the primary tumors in all cases, and of lymph node metastases in five cases. All the primary tumors showed invasion beyond the muscularis propria of the colorectum. Aneuploidy or polyploidy in either Sup or Deep of the primary tumor was found in six of the 11 (54.5%) tumors. Out of the six aneuploid tumors, five were in Dukes' stage C with distant metastases at the time of operation, and four died within one year of surgery. Conversely, out of five diploid tumors, none had distant metastases at the time of operation and two survived for longer than three years after surgery. The DNA ploidy pattern of Deep differed from that of Sup in four out of six aneuploid tumors, and two showed aneuploidy in Sup and diploidy in Deep. All the lymph node metastases in the five tumors had a diploid pattern, although three had aneuploid patterns in the primary tumors. The findings suggest the DNA ploidy pattern of a primary tumor to be correlated with the degree of metastasis at the time of operation or prognosis, but the population of tumor cells having different DNA contents may be apt to change between Sup and Deep in aneuploid tumor.

Adenocarcinoma↗