Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 109 records · Page 6Linked to original sources

PubMed1997

Localized diffuse large-cell lymphoma possibly coated with anti-tumor autoantibody: kappa lambda-dual-positive lymphoma.

We report a case of diffuse large-cell lymphoma which pursued a clinically indolent course while remaining untreated. The tumor cells expressed surface IgG, CD10, CD19 and CD20, but not surface IgM, IgD, IgA, CD5, CD16, CD32 and CD64. In addition, these cells appeared to coexpress kappa- and lambda-light chains on their surface. JH and J lambda genes were monoclonally rearranged, but not the J kappa gene. The present lymphoma was found to have arisen from follicle center cells expressing IgG lambda, while the surface kappa-light chain seemed to be extrinsic. Furthermore, the extrinsic immunoglobulin bearing the kappa-light chain may have belonged to IgG because no surface immunoglobulins other than IgG were detected on the cell surface. Then, the extrinsic IgG may have combined with certain molecules on the tumor-cell surface through its Fab portion because the tumor cells lacked all three receptors for the IgG-Fe portion. Fc gamma RI (CD64). Fc gamma RII (CD32) and Fc gamma RIII (CD16). From these findings and the patient's history of never having received a blood transfusion, we concluded that the present case might be of a B-cell lymphoma possibly coated with an IgG-type autoantibody which appeared to have anti-idiotypic activity.

Adult↗

PubMed1997

Multiple pulmonary nodules in association with pyoderma gangrenosum.

This report describes a patient with extensive pyoderma gangrenosum in whom there were co-existent lung abnormalities. The patient's X-ray showed peripherally sited multiple pulmonary lesions bilaterally. A lung biopsy showed chronic non-specific inflammatory changes with neutrophil and lymphocyte infiltration which were similar to the skin lesions. This case was diagnosed as multiple aseptic nodules in pyoderma gangrenosum. The pulmonary infiltrative shadows were controlled only with prednisolone treatment. Steroid therapy is considered to be the first choice to control pulmonary lesions of this disease.

Anti-Inflammatory Agents↗

PubMed1997

Telomerase activity and cytogenetic changes in chronic myeloid leukemia with disease progression.

Progressive telomere shortening is thought to be important in the regulation of cellular senescence and that the upregulation or reactivation of telomerase activity may be a critical if not rate limiting step in the development of neoplastic cells. To obtain information about telomeres and telomerase activity in hematopoietic neoplasia at various disease stages, we evaluated 54 samples obtained from 41 patients with chronic myeloid leukemia (CML) using a combination of fluorescent-telomeric repeat amplification protocol and an internal telomerase assay standard. The terminal restriction fragment (TRF) lengths in the blast phase was reduced compared to that in the chronic phase (4.53 +/- 0.72 kb vs 6.13 +/- 1.68 kb; P = 0.0005). All samples obtained from CML in the chronic phase (n = 33) had detectable telomerase activity above background, regardless of age. In the blast phase (n = 21), a significant increase of telomerase activity was detected compared to that in the chronic phase (33.84 +/- 37.86% vs 6.08 +/- 3.21; P = 0.016). Among patients in the blastic phase, 50% of patients had moderate to high telomerase activity (>10 relative value), and the remaining patients had telomerase activity higher than that in the normal peripheral blood cells. No significant differences in hematologic findings, duration of chronic phase or blast phase, and telomere length in the blastic phase were noted between these two groups separated by telomerase activity. CML patients with moderate to high telomerase activity had a high frequency of additional cytogenetic changes (P = 0.01).

Adolescent↗

PubMed1997

Vitamin K2 and its derivatives induce apoptosis in leukemia cells and enhance the effect of all-trans retinoic acid.

Geranylgeraniol, a polyprenylalcohol composing the side chain of vitamin K2 (VK2), was previously reported to be a potent inducer of apoptosis in tumor cell lines (Ohzumi H et al, J Biochem 1995; 117: 11-13). We examined the apoptosis-inducing ability of VK2 (menaquinone 3 (MK3), MK4 and MK5) and its derivatives such as phytonadione (VK1), as well as polyprenylalcohols with side chains of various lengths including farnesol (C15-OH; FO), geranylgeraniol (C20-OH; GGO), and geranylfarnesol (C25-OH; GFO) toward leukemia cells in vitro. MK3, MK4, MK5 and GFO (at 10 microM) showed a potent apoptosis-inducing activity for all freshly isolated leukemia cells tested and for leukemia cell lines such as NB4, an acute promyelocytic leukemia (APL)-derived cell line and MDS92, a cell line derived from a patient with myelodysplastic syndrome, although there were some differences depending on the cells tested. In contrast, VK1 showed no effect on any of the leukemia cells. The combination of MK5 plus all-trans retinoic acid (ATRA) resulted in enhanced induction of apoptosis in both freshly isolated APL cells and NB4 cells as compared to each reagent alone. These data suggest the possibility of using VK2 and its derivatives for the treatment of myelogenous leukemias, including APL.

Apoptosis↗

PubMed1997

Ion transport systems in the uptake of 99Tcm-tetrofosmin, 99Tcm-MIBI and 201Tl in a tumour cell line.

The kinetics, intracellular distribution and effects of ion transport inhibitors on the uptake of 99Tcm-tetrofosmin, 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) and 201Tl were investigated in a tumour cell line. Both uptake and washout of the tracers were measured at specific intervals. Cells were treated with ouabain, dimethyl amiloride (DMA) and bumetanide to observe the effects on uptake, while carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used to study the release of the tracers. The tracers showed similar uptake and washout kinetics. Ouabain inhibited 55-67% of 201Tl, 16-22% of 99Tcm-tetrofosmin and 8-14% of 99Tcm-MIBI. DMA inhibited the uptake of both 99Tcm-tetrofosmin (30%) and 99Tcm-MIBI (21%). Bumetanide stimulated the uptake of 99Tcm-tetrofosmin and 99Tcm-MIBI but inhibited that of 201Tl (37%). When cells were pretreated with various combinations of these ion transport inhibitors, the uptake of 201Tl was related to Na+,K+ pump, Na+,K+, 2Cl- co-transport systems, whereas the uptake of both 99Tcm-tetrofosmin and 99Tcm-MIBI was related to the Na+,K+ pump, Na+/H+ antiport systems. Addition of CCCP released 55% and 90% of accumulated 99Tcm-tetrofosmin and 99Tcm-MIBI respectively, indicating that the percentage released was related to mitochondrial uptake.

Amiloride↗

PubMed1997

Protein kinase inhibitor attenuates an increase in endothelial monolayer permeability induced by tumour necrosis factor-alpha.

We questioned the mechanism of the increase in pulmonary endothelial permeability induced by tumour necrosis factor-alpha (TNF-alpha), a cytokine implicated in the pathogenesis of adult respiratory distress syndrome. As a measure of permeability, we determined the albumin transferred across cultured pulmonary endothelial monolayers prepared on a porous filter. The agents evaluated included protein kinase inhibitors H-7 and H-8, a calmodulin antagonist W-7, and protein kinase C (PKC) activators, phorbol myristate acetate (PMA) and SC-9. H-7, more potent in inhibiting PKC than H-8, failed to attenuate the increase in permeability induced by TNF-alpha. Neither PMA nor SC-9 increased permeability. However, H-8, which is a potent inhibitor of cyclic nucleotide-dependent protein kinases, prevented the increase in permeability induced by TNF-alpha. These results suggest that protein kinase other than PKC are involved in the signal transduction in endothelial permeability increase induced by TNF-alpha. Calmodulin pathway may not be implicated in the increase in permeability induced by TNF-alpha.

Albumins↗

PubMed1997

Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study. Multicenter Study Group.

A multicenter randomized controlled study was undertaken in order to determine whether epoetin beta (EPO) ameliorates the anemia in aplastic anemia (AA) patients treated with granulocyte colony-stimulating factor (G-CSF). Enrolled patients were randomized into 3 groups: group C receiving G-CSF alone as the control; group L receiving G-CSF and 200 IU/kg of EPO; group H receiving G-CSF and 400 IU/kg of EPO. Throughout the study, the dose and the administration interval of G-CSF were adjusted to maintain neutrophil counts between 1000 and 5000 microliters EPO was administered subcutaneously for 12 wk as the first step in treatment and when favorable effects were observed over this period, treatment was continued for another 12 wk as the second step in treatment. Significant erythroid responses were defined as increases in untransfused hemoglobin values > 1.0 g/dl or > 50% decreases in RBC transfusion requirements over the treatment period. Of 131 patients enrolled, 88 patients allocated to groups L and H were evaluated for toxicity to EPO and 110 were evaluated for erythroid responses. Four of the 31 patients (12.9%) in group C, 6 of the 41 patients (14.6%) of group L, and 14 of the 38 patients (36.8%) of group H showed erythroid responses in the first step in treatment. The erythroid responses of group H were significantly higher than those of the other 2 groups (p < 0.05). The significant effects of EPO were due to erythroid responses in non-severe AA. Responding patients were significantly different from non-responders with regard to disease severity, hemoglobin concentration, reticulocyte count, serum endogenous erythropoietin levels and serum transferrin receptors; non-severe AA patients were more likely to respond to EPO, and responding patients had lower serum EPO and higher hemoglobin concentration, reticulocyte count and serum transferrin receptors than non-responders. The response rate increased in the second step in treatment, suggesting that long-term treatment improved the efficacy of EPO. No serious side-effects were observed. From these results, we conclude that EPO given in combination with G-CSF is a safe and effective alternative for the treatment of anemia of a subset of AA patients.

Adult↗

PubMed1997

Possible involvement of bone marrow stromal cells in agranulocytosis caused by vesnarinone treatment.

Vesnarinone, an oral therapeutic agent for cardiac failure, causes agranulocytosis as a side effect. To elucidate the mechanism of occurrence of the agranulocytosis, we examined the effect of vesnarinone on granulopoiesis using an in vitro human long-term bone marrow culture system. Addition of vesnarinone to the culture decreased the total number of hematopoietic cells, mainly composed of mature granulocytes and macrophages, but increased the number of granulocyte-macrophage progenitor cells (CFU-GM) and CD33-CD34+ cells as compared with an untreated control. Differentiation of CFU-GM was induced by removing the agent from the culture medium, indicating that the effect of vesnarinone was reversible. The agent did not directly affect CFU-GM in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, treatment of stromal cells with vesnarinone repressed the production of G, GM, M-CSF, suggesting that the agent may cause a hematopoietic disorder, agranulocytosis, through the impairment of stromal cell function.

Agranulocytosis↗

PubMed1997

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis.

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.

Adenoviruses, Human↗

PubMed1997

Two cases of acromegaly in a family.

We report two cases of acromegaly due to pituitary adenoma without any other endocrinopathy in a family. The patients had high plasma GH and were improved by transsphenoidal adenomectomy. Acromegaly is usually a clinical syndrome of sporadic nonfamilial occurrence. The familial occurrence of acromegaly not associated with multiple endocrine neoplasia is very rare. Our patients are unlikely to be associated with the multiple endocrine neoplasia type 1 syndrome. Here we describe two patients with acromegaly, a father and his daughter, and review familial cases reported.

Acromegaly↗

PubMed1997

Diffuse alveolar hemorrhage associated with proteinase 3-specific anti-neutrophil cytoplasmic antibodies.

A 31-year-old man was referred to our hospital for the management of progressive diffuse alveolar hemorrhage associated with renal dysfunction. Leukocytoclastic vasculitis was shown by skin biopsy and crescentic glomerulonephritis was also detected, in addition to positivity for proteinase 3-specific anti-neutrophil cytoplasmic antibodies (PR3-ANCA). The patient was diagnosed as a rare case of PR3-ANCA-positive pulmonary-renal vasculitic syndrome without granulomatous lesions. There was a good response to combination therapy with steroids and cyclophosphamide.

Adult↗

PubMed1997

[Spinal cord ischemia caused by dissecting aortic aneurysm in a patient with acute exacerbation of pulmonary emphysema].

A 61-year-old man with pulmonary emphysema was admitted due to acute exacerbation of chronic respiratory failure and a complaint of chest pain. A chest CT scan on admission showed aneurysmal dissection from the ascending aorta to the descending aorta. Analgesia was noted below the fourth thoracic vertebra, which supplies the accessory respiratory muscles including the intercostal muscles. Even after recovery from circulatory failure, his chest muscles were weak and he could not be removed from mechanical ventilation. An autopsy revealed ischemia of the spinal cord at the T4 level. In contrast, The C3 level of the spinal cord, which supplies the diaphragm, was intact. Paralysis of accessory respiratory muscles including intercostal muscles may have caused the continuation of the respiratory failure. This case shows the importance of accessory respiratory muscles in maintaining chest wall movement in patients with chronic pulmonary emphysema.

Acute Disease↗

PubMed1997

[Possible role of immunocompetent cells on periodic exacerbation of idiopathic thrombocytopenic purpura].

A 44 year-old man was admitted to our hospital in October, 1992 with epistaxis. Fifteen months before admission, thrombocytopenia had been pointed out, but he had no bleeding episode. At admission, neither hepatosplenomegaly nor lymph node swelling was observed. Hematological findings were as follows; WBC 10,000/microliter, Hb 14.0 g/dl, PLT 5,000/microliter, including giant platelets. Platelet associated IgG (PAIgG) was 471 ng/10(7) cells. Bone marrow aspiration revealed normocellularity with moderate increase in the number of mature megakaryocytes, but no dysplastic changes were seen. Biochemical and radiological examinations disclosed neither malignant diseases nor autoimmune diseases. Based on the diagnosis of idiopathic thrombocytopenic purpura, danazol therapy (300 mg/day) was started in November, 1992. After initiation of treatment, the platelet count changed cyclically every 4 weeks. To elecuidate the mechanism of this phenomenon, we periodically evaluated the patient's immunological background. T lymphocyte counts and subset proportions remained almost the same through out the course, whereas NK cell counts and NK activity coincided with the change of the platelet count. These results suggest that in this case NK cells may play a role in the cyclic fluctuation of platelet count by regulating the immune system.

Adult↗

PubMed1997

[Application of measuring 99mTc-MAG3 plasma clearance based on one-compartment model (MPC method) to pediatric patients].

Measurement of 99mTc-MAG3 plasma clearance based on 1-compartment model (MPC method) were applied to 12 pediatric patients and evaluated for the factors which might affect the calculated results. Depth correction is a critical factor for the measurement of renal uptake. Three different equations for estimating renal depth were compared with the real depth measured by ultrasonography. The equation proposed by K. Itoh was suitable though the equations by T. Ito and Raynaud were insufficient. Estimation of distribution volume, which is regarded as circulating plasma volume (CPV), is also critical for the calculation of MAG3 clearance by MPC method. Precisely, hematocrit measured by venous sampling and circulating blood volume (CBV) calculated as 7.5% of body weight are used for estimation of CPV. However, assumed CPV as 5% of body weight was acceptable if the hematocrit was not severely deviated from the normal value. Simplified MPC method utilizing two factors mentioned above gave a positive correlation with Russell's one point sampling method. In conclusion, MPC method is applicable for pediatric patients.

Adolescent↗

PubMed1997

[Essential thrombocythemia in transformation to acute leukemia (FAB-M0) as a natural history from myelofibrosis with t(1;7)].

A 34-year-old man was found to have leukocytosis and thrombocytosis in 1983. In 1988, his leukocyte count was 10,400/microliter, Hb 16.5g and a platelet was 73 x 10(4)/microliter. A bone marrow examination showed megakaryocyte hyperplasia. Essential thrombocythemia (ET) was diagnosed but no treatment was given. In February 1993, anemia and hepatosplenomegaly developed and cytogenetic study of the peripheral blood demonstrated t(1;7) (q10;p10). Myelofibrosis was diagnosed as by bone marrow biopsy. The patient was treated with blood transfusion, oxymetholone and prednisolone, but without effect. In 1995, acute myeloid leukemia developed, and he died in December 1995 due to septicemia. We report here a case of the ET developed myelofibrosis with t(1;7) (q10;p10) anomaly and acute leukemia.

Acute Disease↗

PubMed1997

Effects of vesnarinone on the bone marrow stromal cell-dependent proliferation and differentiation of HL60 cells in vitro.

It has been reported that vesnarinone, a new inotropic agent used in the treatment of cardiac failure, causes agranulocytosis as a side effect. To study the mechanisms by which this complication occurs, vesnarinone was introduced into a coculture system of HL60 and bone marrow (BM) stromal cells, in which HL60 cells were able to differentiate into mature granulocytes with no inducible exogenous factors added to the culture. When HL60 cells were cocultured with the human BM-derived stromal cell line LP101, HL60 cells were induced to differentiate into mature granulocytes, and expression of the mature granulocyte-macrophage surface antigen, CD11b was increased. Conditioned medium (CM) obtained from LP101 cells also showed the capacity to induce the maturation of HL60 cells, in a dose- and time-dependent manner. The differentiation of HL60 cells induced by CM was also determined by morphological analysis, expression of myeloperoxidase, and a nitroblue tetrazolium (NBT) reduction test. When HL60 cells were cocultured with LP101 in the presence of vesnarinone, the CD11b expression was greatly suppressed. CM obtained from vesnarinone-treated LP101 (ves-CM) lost the capacity to induce the differentiation of HL60 cells, at a concentration of 1 microg/mL of vesnarinone. Vesnarinone itself did not affect the proliferation of HL60 cells. Furthermore, the addition of vesnarinone or ves-CM to HL60 cultures incubated with CM did not alter the induction of CD11b expression, suggesting that vesnarinone has no effect on HL60 cells, but that it inhibits stromal cells from producing soluble factor(s) required for the differentiation of HL60 cells to mature granulocytes. All these findings indicate that vesnarinone causes the hematopoietic disorder agranulocytosis, via impairment of stromal function.

Bone Marrow↗

PubMed1997

[Use of a bronchoscope for thoracoscopic observation and diagnosis of pleural plaques].

A 62-year-old man was admitted to our hospital for evaluation of bilateral tumor-like shadows along the ribs. He had been a diamond-grinder for twenty years. Thoracoscopic examination with a flexible bronchoscope revealed many well-circumscribed tumors with shiny, smooth, convex surfaces on the parietal pleura. The biopsy specimen had hyaline collagen with no cellular components. Based on these findings the tumors were diagnosed as pleural plaques. Cases of pleural plaques are usually followed up with chest radiography only, but the clinical course may be complicated by malignant mesothelioma and other malignant disease. To differentiate these conditions we performed biopsy during intrathoracic observation. The flexible bronchoscope can be useful in such procedures because it is relatively easy to operate and the procedure is relatively non invasive.

Asbestosis↗

PubMed1997

[Successful treatment of chronic eosinophilic pneumonia with suplatast tosilate].

The patient was a 59-year-old woman who complained of coughing, sputum production, and dyspnea. Abnormal moving shadows were found by chest radiography. There was prolonged eosinophilia in blood. Eosinophilia was also found in bronchoalveolar lavage fluid, and examination of a specimen obtained by transbronchial lung biopsy revealed eosinophil infiltration in alveolar septal walls, which led to a diagnosis of chronic eosinophilic pneumonia. Because of an attack of bronchial asthma and a high level of IL-5 in serum on admission, the patient was given suplatast tosilate. Symptoms were relieved, eosinophil counts in blood and in bronchoalveolar lavage fluid decreased, and the radiographic abnormality disappeared. The patient was not treated with steroids, and there has been no reccurrence to date, one year after discharge.

Anti-Allergic Agents↗