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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 181 records · Page 10Linked to original sources
PubMed1995

Long-term effects of embryo freezing in mice.

Embryo cryopreservation does not induce clear-cut anomalies at detectable rates, but several mechanisms exist for nonlethal damage during the freeze-thaw process, and the risk of moderate or delayed consequences has not been extensively investigated. In a long-term study including senescence, we compared cryopreserved and control mice for several quantitative traits. Significant differences were seen in morphophysiological and behavioral features, some of them appearing in elderly subjects. Thus, apart from its immediate toxicity, embryo cryopreservation, without being severely detrimental, may have delayed effects. These results, consistent with other findings, question the neutrality of artificial reproductive technologies and draw attention to the preimplantation stages in developmental toxicology.

Age Factors↗
PubMed1995

Analysis of bone marrow and peripheral blood immunoregulatory lymphocytes in patients with myelodysplastic syndrome.

The cell surface phenotype of immunoregulatory lymphocytes in bone marrow (BM) and peripheral blood (PB) in myelodysplastic syndrome (MDS), a stem cell disorder, was analyzed. Mononuclear cells from 25 patients with refractory anemia (RA) and nine with RA with an excess of blasts (RAEB) were characterized by two-color flow cytometry using various monoclonal antibodies. No significant change of CD3+, CD4+, and CD8+ cells in PB, but a decrease of the percent of positive cells for CD8++ among the total lymphocyte (%CD8++) was noticed in RA patients. On the other hand, in BM of RA patients, a decrease in the number of CD4+ cells, but not CD8++ cells, was noted. In RAEB patients, the absolute numbers of CD3+, CD4+, CD8+, and CD8++ cells in BM were decreased; however, the ratio of these lymphocytes was not changed. No change was observed among the CD4+ subsets in PB of RA or RAEB patients. In BM, a decrease in percentage of CD4+CD45RA+ (%CD4+CD45RA+; naive cell) and increases in CD4+CD45RO+ (%CD4+CD45RO+; memory cell) and CD4+CD29+ (%CD4+CD29+; helper/inducer) among CD4+ cells were found in both RA and RAEB patients. Analysis of the CD8++ subset showed an increased number of CD8++CD11a+ cells (activated CTL) in both BM and PB of RA patients, but not of RAEB patients. Furthermore, increments in CD56+ and CD16+ cells among CD3- cells (natural killer; NK cells) were seen in RA patients but not in RAEB patients. It remains unclear whether lymphocytes in MDS patients were involved in the abnormal (MDS) clones, but our results regarding the increments of CD8++CD11a+ and NK cells in RA patients suggest that the mechanism of immune surveillance against the abnormal MDS clones was activated in these RA patients, but not in RAEB patients. Further investigation is required to clarify the functions of these immunoregulatory lymphocytes in MDS patients.

Adult↗
PubMed1995

Double-minute chromosomes appearing in a patient with myelodysplastic syndrome with disease evolution.

We present the first case of a myelodysplastic syndrome (MDS) demonstrating an association between the appearance of double-minute chromosomes (dmin) and disease progression. This 59-year-old Japanese woman showed a deletion of the long arm of chromosome 5 [del(5)(q21q34)] and monosomy 9, when she was diagnosed as having refractory anemia with an excess of blasts (RAEB). Subsequential cytogenetic analyses demonstrated that the neoplastic cells in the peripheral blood had six copies of dmin, when the disease progressed into RAEB in transformation (RAEBt). This cytogenetic change was consistently observed when the patient developed the leukemia phase. The findings in this case suggest that the appearance of dmin may be linked to progression of the disease.

Chromosome Aberrations↗
PubMed1995

Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum: the first case report from Japan.

We report a case of lymphocutaneous syndrome caused by Nocardia otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who underwent long-term therapy with prednisolone for bronchial asthma. Histological examination showed granulomatous reaction with multiple polymorphonuclear leukocytes and revealed a Gram positive filament in the dermis. Gram-positive, slightly acid-fast branched filaments were also found in the smear of the purulent material. The cell wall constituents of the isolate were meso-diaminopimelic acid, arabinose, and galactose; the mycolic acid pattern of the isolate was Nocardia type. The organism decomposed xanthine and hypoxanthine, but not tyrosine or casein, which distinguished it from N. asteroides and N. brasiliensis. The skin lesions responded to minocycline and later to a combination of doxycycline and ofloxacin. This primary lymphocutaneous nocardiosis due to N. otitidiseaviarum is the first in Japan.

Aged↗
PubMed1995

[Therapeutic evaluation of combination therapy using human native immunoglobulin preparation for i.v. administration, with antibiotics and G-CSF in severe infections in the field of internal medicine].

A human native immunoglobulin liquid preparation for intravenous injection, was used in combination with antibiotics and G-CSF to study its efficacy and safety in 49 patients with severe infections (Granulocyte counts were or= 38 degrees C) which had not responded to antibiotic and G-CSF therapy of a 3-day or more duration. As a result of the Committee judgment, 49 patients were included in this study; 30 (61.7%) were included in efficacy and safety analysis. The analysis of 30 patients consisted of 9 patients (30.0%) with suspected septicemia, 5 (16.7%) with pneumonia, and 4 (13.3%) with septicemia. All patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of Immunoglobulin preparation was judged by the doctors in charge to be "excellent" and "good" in 70.0% of the total cases. The rate of effectiveness was calculated from the results of the Committee judgment was 83.3% when "excellent" and "good" cases were included. No side effects were observed in all cases. Our results suggest that the immunoglobulin in combination with G-CSF is very effective on patients with severe infections.

Adult↗
PubMed1995

Fat embolism syndrome caused by vegetable oil injection.

We present a case of fat embolism syndrome following vegetable oil injection for augmentation mammaplasty. Although vegetable oil is a stable neutral fat under usual storage conditions, it caused fat embolism and pulmonary injury in this patient. We investigated this mechanism by compound analysis of the injected oil, transbronchial lung biopsy and special staining of alveolar macrophages. This is the first description of the human response to vegetable oil injection. These data should aid in the investigation of the side effects of many types of lipids which may be applied to humans for various purposes in the future.

Adult↗
PubMed1995

[Clinical course of a HIV-seropositive patient with thrombocytopenia and hypergammaglobulinemia who was initially screened by annual complete physical examination].

A 57-year-old man was admitted because of hypergammaglobulinemia which was initially pointed out by annual complete physical examination. No significant abnormal findings were observed except polyclonal hypergammaglobulinemia at that time (IgG; 2,662 mg/dl, IgA; 422 mg/dl). Seven months later, he has progressed to show thrombocytopenia. The laboratory data showing the reduction of peripheral CD 4-positive T cells (CD 4; 0.2 x 10(9)/l, CD 4/8 ratio; 0.19) and positive serum HIV antibody revealed that his hypergammaglobulinemia and thrombocytopenia were resulted from HIV infection. The peripheral platelet count decreased to 28 x 10(9)/l at minimal point, however, it recovered to 160 x 10(9)/l within 7 months without treatment. His good performance status has been still maintained over 4 years. His whole clinical course suggests that there is no significant correlation between peripheral platelet counts, serum gammaglobulin levels or the amounts of PAIgG in this case. This case proposes that we should also consider a possibility of HIV infection for the patients showing hypergammaglobulinemia.

HIV Seropositivity↗
PubMed1995

[The effects of recombinant human granulocyte colony-stimulating factor on protracted neutropenia in patients with acute myelogenous leukemia. (rG.CSF Clinical Study Group)].

A clinical study to investigate the efficacy and safety of recombinant human G-CSF (rG.CSF) was performed in patients with acute myelogenous leukemia who had had protracted neutropenia. The drug was administered d.i.v. at a dose of 5 micrograms/kg. Sixty-four patients entered the study, of whom 61 patients were evaluable for safety and 58 patients evaluable for efficacy. The treatment produced an early recovery in neutrophil count in the patients who had had protracted neutropenia (< 1,000/microliters) of over 10 days. Among relapsed cases and cases showing > 20% blasts in the bone marrow, many showed blast stimulation in response to rG.CSF, suggesting difficulty in attaining complete remission by subsequent chemotherapy in such cases. The present data indicates that it is desirable to use the drug in lower-blast-count states in order to attain safe and sufficient therapeutic effects in patients with acute myelogenous leukemia who have had protracted neutropenia.

Adolescent↗
PubMed1995

[A randomized controlled study of rG.CSF in patients with neutropenia after induction therapy for acute myelogenous leukemia. (rG.CSF Clinical Study Group)].

A randomized treated/non-treated study of rG.CSF (5 micrograms/kg/d, d.i.v.) in patients with acute myelogenous leukemia was conducted to assess its efficacy on fever (> or = 38 degrees C) or documented infection after induction therapy. Of 95 patients enrolled, 46 patients were evaluable for safety and 43 for efficacy in the treated group of 47 patients while 37 of 48 patients were eligible for data analysis in the untreated group. Mare patients showed a recovery in the blood neutrophil count (to > 1,000/microliters) during rG.CSF treatment (14 days) than in the non-treated group (p = 0.039) while the number of febrile patients and duration of fever did not significantly differ between the two groups. The treatment with rG.CSF enabled an early recovery in neutrophil count in the patients with neutropenia and overt signs of infection after induction therapy, but there was no hastened allevistion of symptoms of infection in these patients.

Adolescent↗
PubMed1995

[A randomized double-blind controlled study of recombinant human granulocyte colony-stimulating factor in patients with neutropenia induced by consolidation chemotherapy for acute myeloid leukemia. (rG.CSF clinical study group)].

A multicenter, randomized, double-blind controlled study was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rG.CSF) in reducing infectious morbidity and neutropenia induced by consolidation chemotherapy for acute myeloid leukemia (AML). One hundred and twenty-four eligible patients were randomized to receive either rG.CSF (5 micrograms/kg/d d.i.v.; 59 patients) or placebo (65 patients) for 14 days from the day after chemotherapy. All of them were included in the safety analysis, while 57 patients receiving rG.CSF and 64 patients receiving placebo were included in the efficacy analysis. The duration of neutropenia as well as the incidence of fever and febrile neutropenia, and frequency of antibiotic therapy required, were all significantly reduced in the rG.CSF group. No serious adverse reactions were encountered; there was no significant difference between the two groups in terms of incidence of adverse events. These results demonstrate that rG.CSF is beneficial to alleviate neutropenic episodes induced by consolidation chemotherapy in patients with AML.

Adolescent↗
PubMed1995

Tyrosine phosphorylation and activation of focal adhesion kinase (p125FAK) by BCR-ABL oncoprotein.

Focal adhesion kinase (p125FAK; FAK) is a protein tyrosine kinase that is tyrosine-phosphorylated in response to v-src-mediated transformation, cell adhesion, and stimulation with neuropeptides. To elucidate a possible functional relationship between FAK and BCR-ABL oncoprotein detected in Philadelphia chromosome-positive (Ph+) leukemias, we investigated the tyrosine phosphorylation state of FAK in a murine growth factor-dependent cell line and in its stable human bcr-abl cDNA transfectant. In interleukin-3 (IL-3)-dependent NFS/N1.H7 cells, tyrosine phosphorylation of FAK was not detected after stimulation with either IL-3 or Steel factor (SLF), both of which involve Ras-mediated signaling pathways. However, stable gene transfection with p210bcr-abl cDNA into H7 cells made these cells growth factor-independent for proliferation and resulted in constitutive tyrosine phosphorylation and kinase activation of FAK. Constitutive phosphorylation and activation of FAK was also observed in all Ph+ leukemia cell lines examined--that is, K562, TS9;22, and YS9;22, which express p210BCR-ABL, and NALM-21 and OM9;22, which express p185BCR-ABL. Ph-negative (Ph-) cell lines, such as MO7e and JM, did not show any detectable tyrosine phosphorylation of FAK. FAK phosphorylation in BCR-ABL-expressing cells was inhibited in a dose-dependent manner by cytochalasin D, a reagent that disrupts the intracellular network of actin filaments. However, no suppression of kinase activity or protein expression of BCR-ABL was observed after treatment with cytochalasin D. A physical association between BCR-ABL and FAK was not apparent. These data suggest that BCR-ABL may be involved in the activation of FAK. Moreover, FAK may be distinct from components in Ras-mediated signaling cascades that are activated by stimulation of myeloid cells with various cytokines.

Animals↗
PubMed1995

Incidence and characteristics of clonal hematopoiesis in remission of acute myeloid leukemia in relation to morphological dysplasia.

We studied 34 patients in remission of acute myeloid leukemia (AML) by performing clonal analysis of peripheral blood polymorphonuclear (PMN) cells and mononuclear (MN) cells, using X-linked DNA polymorphisms, in conjunction with the assessment of morphological myelodysplastic changes, performed by a scoring method. Nine patients demonstrated a non-random or skewed X-chromosome inactivation pattern in PMN cells. Three of these nine patients had an apparently random pattern in MN cells (group A), whereas the remaining six patients demonstrated no difference between the inactivation patterns of PMN and MN cells (group B). The PMN cells of the other 25 patients showed a random X-chromosome inactivation pattern, and the patterns of the PMN cells did not differ from those of the MN cells (group C). The scores for myelodysplasia were high (> or = 4) in all three patients in group A, intermediate (2-3) in two patients and low (score < 2) in four patients in group B, and intermediate in five patients and low in 20 patients in group C. The duration of remission in patients with a myelodysplasia score of > or = 2 was significantly shorter than that of patients with a score of < 2 (P < 0.01). We conclude that clonal remission actually occurs with myelodysplastic features in some patients with AML (around 10%, group A). It is possible that this clonal analysis may not be sensitive enough to detect the preleukemic clone with myelodysplastic features when this clone constitutes only a minor population of remission hematopoiesis. To further elucidate the biology of such preleukemic clones it is essential to develop more sensitive molecular methods for the detection of genetic abnormalities specific to preleukemic hematopoiesis.

Adolescent↗
PubMed1995

[The expression pattern of transcription factors (GATA, SCL) and biological characteristics in various leukemia cells].

We have studied gene expression of GATA-1, GATA-2, and SCL, which are known as cell-specific transcription factors, in 110 various leukemias consisted of 76 patients with acute myeloid leukemia (AML), 19 with acute lymphoblastic leukemia (ALL), and 15 with chronic myeloid leukemia (CML) in blast crisis by the revearse transcription-polymerase chain reaction assay. Accordingly, we divided into three groups. Group I (GATA-1+SCL+): patients with AML exhibiting phenotypic characteristics of erythroid or megakaryocytic lineage and most of CML myeloid blast crisis were included. Group II (GATA-1+, SCL-): Not only CD7-positive and CD19-positive AML, but also a part of Ph+ALL demonstrated this pattern. Leukemia in this group is considered to have a capability to differentiate into myeloid and lymphoid lineages. Group III (GATA-1-, SCL-): patients in this group consisted of leukemias which are differentiated into specific cell-lineages, either myeloid or lymphoid, when compared to groups I or II. Our data suggest that the expression pattern of transcription factors reflects lineage potential in leukemia cells, leading to classification of leukemias.

DNA-Binding Proteins↗
PubMed1995

[The enzymatic character of myeloma cell].

Thymidine kinase (TK) is a cellular enzyme required for the incorporation of thymidine into DNA. It catalyses the conversion of deoxythymidine to deoxythymidine monophosphate (dTMP). The synthesis of dTMP from deoxythymidine is called the salvage pathway. There are two types of thymidine kinase, distinguished by there biochemical and physico-chemical characteristics. Cytosolar TK is found in dividing cells in stages G1-S. Mitochondrial TK is found in mitochondria. Serum thymidine kinase (S-TK) levels can be determined by the use of a radioenzyme assay method. These are increased in proliferating cells (S phase). It is a useful tool for the clinical evaluation, staging, and follow-up of patients with multiple myeloma.

Adult↗
PubMed1995

[Analysis of T cell subsets in autoimmune hemolytic anemia patients].

To clarify a role of immunoregulatory T cells in the pathophysiology of autoimmune hemolytic anemia (AIHA), we investigated T cell subsets in the peripheral blood of 15 patients with AIHA by two color analysis using flow cytometry. Consequently both CD4+ cells and CD4+CD45RA+ cells decreased in proportion, irrespective of the disease activity (active or remission phase). CD4+CD45RA+ cells are regarded as naive T cells. Incidentally the ratio of CD45RA+ cells in CD4+ cells also fell in the low level in active phase, but it recovered to the normal ratio in remission. On the other hand, CD8+ cells and CD8+ +S6F1+ cells that may represent activated cytotoxic T lymphocytes increased in active phase and then both entered the normal range in remission. These findings suggest that AIHA could be caused partly by the alternative balance of CD4+CD45RA+ cells probably constituting a member of IRT and moreover by the activation of CTL.

Anemia, Hemolytic, Autoimmune↗