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Biomedical subjects

T Yonezawa

Publications and source records attributed to T Yonezawa.

At least 19 recordsLinked to original sources
PubMed1992

Effects of splenectomy on immune thrombocytopenic purpura in (NZW x BXSB) F1 mice: analyses of platelet kinetics and anti-platelet antibody production.

Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham-operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy.

Animals↗
PubMed1992

Elevated serum manganese superoxide dismutase in acute leukemias.

We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1.

To determine the mechanism by which platelet counts increase after corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we studied the platelet kinetics using prednisolone (PDN)-treated ITP-prone mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40 days), but not in nontreated controls (0.60 +/- 0.24 days, P less than .01). No increase in platelet production (platelet turnover) was found in PDN-treated W/B F1 mice, but significant decreases in platelet-associated antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted. Studies on organ localization of radiolabeled platelets showed that hepatic uptake significantly decreased in the treated W/B F1 mice, but not in nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-endothelial phagocytic activity in W/B F1 mice, we studied in vivo clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. W/B F1 mice treated with PDN showed a marked impairment of their ability to clear these cells, although PDN had little effect on the number of splenic or hepatic macrophage Fc gamma receptors. These results and our previous findings of splenectomy suggest that PDN improves platelet counts not only by suppressing systemic reticulo-endothelial phagocytic function but also by reducing antibody production.

Animals↗
PubMed1992

Glycosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation.

Castanospermine (CSP), an inhibitor of alpha-glucosidase, enhanced immunoglobulin (Ig) release in a Staphylococcus aureus Cowan I (SAC)-induced lymphocyte culture (Scand. J. Immunol. 1990. 32: 529). In a pokeweed mitogen (PWM)-human lymphocyte culture, unlike the SAC-stimulated system, CSP strongly decreased the number of IgG-, IgA- and IgM-secreting cells as well as that of Ig-bearing cells. Peripheral blood lymphocytes treated with swainsonine, a mannosidase II inhibitor, or with neuraminidase also showed a reduced response to PWM. In cross-culture experiments, only a mixture of B cells pretreated with either agent and untreated T cells showed such a suppressive effect. Adhesion was decreased between B cells treated with either agent and untreated T cells, but not between treated T cells and untreated B cells. These results demonstrate that a certain alteration in B cell membrane oligosaccharides inhibited the T cell-B cell adhesion in the PWM culture, leading to an arrest of B cell maturation. Considering that these inhibitors eventually prevent terminal sialic acid addition, the present study provides evidence that sialic acids on B cell surface oligosaccharides play a biological role in the T cell-B cell interaction.

B-Lymphocytes↗
PubMed1992

Impaired suppressor function of T cells induced by autologous mixed lymphocyte reaction in patients with idiopathic thrombocytopenic purpura.

Autologous mixed lymphocyte reaction (AMLR)-induced suppressor function was studied in 12 patients with chronic idiopathic thrombocytopenic purpura (ITP). The function was found to be significantly impaired (20 +/- 55%; p less than 0.005) compared with normal subjects (69 +/- 25%). AMLRs in these patients were significantly decreased (p less than 0.05) compared with normal subjects. There was no significant correlation between AMLR-induced suppressor function and platelet counts. Nine patients were studied for AMLR-induced suppressor function before and after splenectomy. The platelet counts increased significantly as a result of splenectomy, but the AMLR-induced suppressor function showed no significant improvement. The results of this study suggest that suppressor dysfunction in ITP may be an immunologic defect irrespective of disease activity. We consider that this abnormality may reflect in vivo failure of the immunoregulatory (feedback) mechanism in ITP.

Adult↗
PubMed1992

Growth inhibition of RPMI 8226 human myeloma cells by peripheral blood lymphocytes.

To clarify the components of cellular immunity responsible for defense against the clonal development of myeloma cells, we tested the capacity of human peripheral blood lymphocytes (PBLs) to inhibit the growth of 3 human myeloma cell lines (RPMI 8226, OPM-1, and OPM-2). RPMI 8226 was found to be sensitive to PBLs, showing almost complete growth arrest when cultured with PBLs for 72 h. Inhibition of the growth of RPMI 8226 cells required direct cell-to-cell contact but not presensitization of the PBLs to the target cells, and did not depend on the generation of soluble factors. CD3+, CD4-, CD8- and CD16- cells were found to be the major subset contributing to inhibition of the growth of RPMI 8226 cells, and this growth inhibition was cytostatic rather than cytotoxic. These characteristics distinguished it from growth inhibition mediated by the natural killer system. Impaired PBL-mediated growth inhibition of RPMI 8226 cells was found in patients with various hematologic diseases, including myeloma. It therefore appears that the CD3+, CD4-, CD8- and CD16- cell subset might be involved in tumor immunity in myeloma.

Antibodies, Monoclonal↗
PubMed1992

[Clinical effects of cefodizime in severe infections complicated with hematological diseases. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections accompanying hematological diseases were treated with cefodizime (CDZM). CDZM was administered by intravenous injection at daily doses ranging from 2 g to 8 g for about 3 to 18 days. Clinical efficacies of CDZM were excellent in 30 cases, good in 37 cases, fair in 1 case and poor in 53 cases. The efficacy rate was 55.4%. The efficacy rate was 56.4% in patients from whom causative organisms were not identified. The efficacy rate against Gram-negative bacteria (66.7%) was higher than that against Gram-positive bacteria (28.6%). No significant differences in the efficacy rates were found among groups of patients with different initial neutrophil counts (less than 100, 100-499, and over 500/microliters). Skin eruption caused by CDZM was observed in 2 patients (1.5%). Hepatic disorders, renal dysfunction and urinary test abnormality (protein and urobilinogen) were observed in 7 (5.0%), 1 (0.7%) and 1 (0.7%), respectively. Therefore, CDZM was considered to be a clinically useful antibiotic for severe infections complicated with hematological diseases.

Adolescent↗
PubMed1992

[Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.

Adolescent↗
PubMed1992

[Therapeutic effects of meropenem against severe infections in patients with hematopoietic disorders. Hanshin Study Group of Hematopoietic Disorders and Infection].

The efficacy and the safety of meropenem (MEPM), a newly developed carbapenem antibiotic, were investigated in 150 patients with severe infections complicated with hematopoietic disorders. 1. Clinical responses in 132 patients who were evaluable for effectiveness were excellent in 33 patients, good in 45, fair in 10 and poor in 44, with an efficacy rate of 59.1%. 2. The efficacy rate in patients who had previously been treated with the other antibiotics was 51.2%, while that in patients who had not been thus treated was 62.9%. 3. The efficacy rate in patients whose neutrophil counts increased during the therapy with MEPM was higher than that in patients whose neutrophil counts did not increase. The efficacy rate in patients whose neutrophil counts during the therapy were below 100/mm3 was 48.1%. 4. Out of 150 cases, side effects were observed in 4 patients, 3 with eruption and 1 with jaundice. Abnormalities in laboratory test results on liver functions were noted in 8 patients. These results indicate that MEPM is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

Adolescent↗
PubMed1992

[Therapeutic effects of cefclidin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however.

Adolescent↗
PubMed1992

[Late phase II study of MST-16 (sobuzoxane) efficacy for malignant lymphoma].

A late phase II study with MST-16 for malignant lymphoma was performed with the collaboration of 11 institutions belonging to the Hanshin Hematological Disease Treatment Research Group. Out of a total 40 patients entered into the study, 37 cases (33 of NHL and 4 HD) were evaluated for efficacy and 27 cases for side effects. The response rate was 29.7% (2 cases of CR and 9 PR). The factors affecting response rate were histological classification, phenotype of tumor cell surface and stage of disease. Bone marrow suppression and G-I disorders were the main toxicities observed, but they disappeared by the cessation of MST-16 treatment.

Adult↗
PubMed1992

[A successful treatment of coronary arteriovenous fistula with Symbas procedure].

A successful treatment of coronary arteriovenous fistula with intraoperative echocardiogram and Symbas procedure is presented. The patient, a 2-year-old male, had been suffering from concealed congestive heart failure from his birth. The cardiac catheterization and angiogram revealed coronary arteriovenous fistula from LAD to right ventricle with large coronary aneurysm. In the operation, no fistula vessels were noted on the cardiac surface. Then, the intraoperative echocardiography was performed, and the fistula pour into right ventricle with aneurysm was found in the myocardium. The fistula was closed with Symbas procedure, and excellent closure could be checked with the intraoperative echocardiogram, too. After this operation, he got well under anticoagulant treatment with "ticlopidine".

Arteriovenous Malformations↗
PubMed1992

[Co-operative on salvage chemotherapy with VP-16 for malignant lymphoma. Hanshin Study Group on Treatment for Hematological Disorders].

Forty one patients with refractory malignant lymphoma were treated with a combination of VP-16, ACM, BH-AC, MTX and PDN as a salvage chemotherapy. These patients were either resistant to frontline therapy or refractory in their relapses. Three patients (7%) achieved a complete remission and 14 patients (34%) attained a partial remission. An overall response rate was 41%. Major toxicities were myelosuppression, nausea, and vomiting. However, they were well tolerated. This regimen has been effective in the treatment for the patients with refractory malignant lymphoma.

Aclarubicin↗
PubMed1991

Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells.

The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought to play an important role in hematopoiesis. In a series of human acute myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and its product was studied by means of Northern blot and immunoblot analyses. The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases the product of the c-kit proto-oncogene was detected by immunoblotting with anti-c-kit antibody. The expression of c-kit transcripts and protein was barely detectable in normal bone marrow cells as a control. The expression of c-kit transcript did not correlate with the French-American-British classification nor clinical manifestations. In 6 of 11 cases that expressed c-kit product, AML cells were found to proliferate in response to recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the synergistic stimulation of AML cells was observed by rhSCF and granulocyte-macrophage colony-stimulating factor. Immunoblotting with anti-phosphotyrosine antibody showed that the c-kit receptor protein was detectably phosphorylated in 7 of 12 cases tested before the stimulation with rhSCF, while the rhSCF treatment resulted in an increased tyrosine phosphorylation of c-kit in AML cells. These results indicate that c-kit proto-oncogene is expressed in most cases of AML and is functional in terms of supporting proliferation.

Blotting, Northern↗
PubMed1991

Pleomorphic xanthoastrocytoma. Ultrastructural, immunohistochemical, and DNA cytofluorometric study of a case.

A case of right frontal pleomorphic xanthoastrocytoma that occurred in a 7-year-old boy is reported clinicopathologically. The patient underwent surgery on September 29, 1988. Histologic diagnosis of pleomorphic xanthoastrocytoma was made because, in addition to the unique pleomorphic histologic features, positive glial fibrillary acidic protein in immunohistochemical staining and characteristic ultrastructural features, i.e., cytoplasmic intermediate fibrils and lipid vacuoles, basal lamina, and abundant reticulin networks were demonstrated. The DNA cytofluorometric analysis of the nuclei of the tumor cells disclosed the main mode to be diploid with polyploid classes (4, 8, 16, and 32C) without any aneuploidy. Despite the presence of many pleomorphic nuclei, DNA histogram of the tumor disclosed very few DNA synthetic cells indicating a biologically inactive nature of the tumor. The patient is still alive and totally asymptomatic 20 months postoperatively.

Astrocytoma↗
PubMed1991

Monocytoid B-cell lymphoma arising in extranodal organs.

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.

Aged↗
PubMed1991

Thermotolerance in regional hyperthermia in vivo--an experimental study using the MH134 tumor.

In the clinical application of hyperthermia, determining the thermotolerance that influences the anti-tumor effect is an important problem. The purpose of this study was to investigate the methods of induction and disappearance of thermotolerance in vivo. After transplanting MH134 cancer cells into the paws of C3H mice, local hyperthermia with warm water was administered, and the movement of thermotolerance in vivo studied in terms of the heating intervals and tumor growth times. When the first heating was applied on the 8th day after transplantation, thermotolerance appeared within 1 hour, increasing gradually to reach a maximum at 18 hours, after which it decreased gradually and disappeared after 48 hours. When the first heating was applied on the 13th day after transplantation, which fell during the rapid tumor proliferation period, the movement of thermotolerance presented a similar pattern of appearance and disappearance. The results of this study made it clear that there was no difference in the movement of thermotolerance between the two periods even though each had a different rate of tumor proliferation.

Animals↗