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Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 235 records · Page 13Linked to original sources
PubMed1991

Biosynthesis and secretion of beta-thromboglobulin by a human megakaryoblastic cell line (MEG-01).

The de-novo synthesis and secretion of beta-thromboglobulin (BTG) by a human megakaryoblastic cell line (MEG-01) were studied by measuring and immunoblotting of BTG in culture supernatant and immunoprecipitation of radiolabeled BTG synthesized after incubation with [35S]methionine. It was demonstrated that BTG synthesized by MEG-01 was secreted into culture media in a monomer form having a molecular weight of 8,800. Furthermore, we purified BTG from culture medium of MEG-01 with a heparin affinity column and compared BTG from MEG-01 with that from normal platelets. The molecular weights of BTG purified from both sources were 8,800 using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). These results provide direct evidence for the synthesis and secretion of BTG by megakaryocytes.

Blood Platelets↗
PubMed1991

Establishment and characterization of human medulloblastoma xenograft line.

A new xenotransplantable tumor line, MED-FU, was derived from a 6-year-old female patient with cerebellar medulloblastoma. This tumor was grown in nude mice as serially transplantable subcutaneous xenografts composed of small round cells with hyperchromatic nuclei and scant cytoplasm. Many rosettes and mitoses were observed. Immunohistochemically, glial fibrillary acidic protein (GFAP), S-100 protein, and neuron specific enolase (NSE) were not detected. The doubling time of the subcutaneous tumors was 6.8 days. Highly concentrated polyamines were detected in the tumor tissue and serum of tumor-bearing mice. This xenotransplanted tumor line, MED-FU, is considered to provide an available experimental model for the study of human medulloblastoma.

Animals↗
PubMed1991

[Laboratory and clinical studies on imipenem/cilastatin sodium plus amikacin sulfate in patients with severe infections complicating hematological disorders].

Imipenem/cilastatin sodium (IPM/CS) and amikacin sulfate (AMK) were administered to 111 patients with severe infections complicating hematological disorders. Of the 111 patients, 93 were included in the present analysis of efficacy and 108 in that of safety. Twenty patients were evaluated as excellent, 37 as good, 8 as fair, and 28 as poor, with an overall rate of effectiveness of 61.3% (57/93). The synergistic interaction of IPM and AMK against clinical isolates (6 strains) was assessed in vitro using the checker board technique. Synergistic and additive effects were observed in 66.7% and 33.3% of the samples, respectively. Side effects were observed in 9 patients and abnormal laboratory test results in 2. These disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS and AMK. From the above findings, IPM/CS with AMK is considered to be a useful antibiotic combination for the treatment of severe infections complicating hematological disorders.

Adolescent↗
PubMed1991

[Selective enhancement of tumor blood flow and drug delivery to brain tumors in experimental rat gliomas under angiotensin II-induced hypertension].

Regional blood flow of brain tumors and normal brain tissue of rats before and during angiotensin II (AT II)-induced hypertension were measured using an electrolytic flowmeter and a laser flowmeter. Etoposide concentration in the tumor and brain tissue after intracarotid administration were also measured in brain tumor bearing rats with or without AT II-induced hypertension. A suspension of 5 x 10(5)/10 microliters 9L gliosarcoma cells was inoculated into the left caudate-putamen of CD Fischer 344 rats. Before induced hypertension, regional blood flow of the tumor (28.2 +/- 2.6 ml/100 g/min; mean +/- SEM) and the contralateral caudate-putamen (23.0 +/- 1.8 ml/100g/min) in the tumor bearing rats were significantly lower than that of the caudate-putamen (43.9 +/- 4.1 ml/100g/min) in the normal rats (p less than 0.01). Intravenous administration of AT II at a dose of 0.4-0.6 microgram/body/min increased the mean arterial blood pressure from 96.5 +/- 4.7 mmHg to 138.0 +/- 3.6 mmHg. AT II-induced hypertension resulted in an approximate 1.8(1.1 - 3.6)-fold increase in the regional tumor blood flow. On the other hand the regional blood flow of the contralateral caudate-putamen was slightly decreased at the rate of 6%. The mean concentration of etoposide with AT II-induced hypertension in the tumor tissue was 2.2-fold higher than that without AT II-induced hypertension. However, etoposide delivery to normal brain tissue was small. From these results, induced hypertension with intravenously administrated AT II selectively increase the tumor blood flow and drug delivery to brain tumor tissue. Intracarotid chemotherapy with AT II-induced hypertension might contribute to enhance therapeutic effect of malignant brain tumors.

Angiotensin II↗
PubMed1991

[Myelodysplasia predominantly involving in megakaryocytic lineage successfully treated with low-dose Ara-C].

A 17 year old male was admitted because of pancytopenia. Bone marrow aspiration revealed myelodysplasia, no increase of blast cells and excessive expansion of megakaryocytic lineage. Although mild increase of bone marrow reticulin fiber was observed, no hepatosplenomegaly was recognized. Therefore he was diagnosed as refractory anemia (RA) or MDS with myelofibrosis and treated with low dose Ara-C regimen. Remission was achieved in June 1987, but the relapse occurred in Oct. 1987. His bone marrow at the relapse showed more remarkable dysplastic change than before. Sequential bone marrow examinations thereafter, revealed an increase of megakaryocytic lineage, especially immature dysplastic megakaryocytes, leading to the appearance of the abnormal megakaryoblasts (detected with anti GP IIb/IIIa antibody) as well as uncharacterized blast cells in his terminal stage. Transformation from MDS to megakaryocytic leukemia was strongly suggested. He died of severe pneumonia in March 1989. The invasion of abnormal immature megakaryocytic cells including megakaryoblasts was observed in liver, spleen and lymph nodes at autopsy. There are several reports on cases having a common hematological features such as 1) pancytopenia in peripheral blood, 2) myelodysplasia, 3) excessive growth of megakaryocytic lineage, 4) myelofibrosis without hepatosplenomegaly, although other clinical features were different. We propose all these cases should be reviewed at the point of MDS mainly involved in megakaryocytic lineage.

Adolescent↗
PubMed1991

[A case of paraganglioma in the posterior mediastinum].

A case of non-functioning aortico-sympathetic paraganglioma originating from left posterior mediastinum in a 34-year-old man is reported. He was found to have an abnormal shadow on the chest X-ray of an asymptomatic. His blood pressure and serological examination were within normal range on admission to our hospital. At thoracotomy a bronze 5 x 5 x 5 cm mass was recognized at the costovertebral sulcus related to the 1st sympathetic trunk. Histological examination of the surgical specimen showed that it was a paraganglioma, and neurosecretary granules were found on Grimelius staining microscopic examination. In the Japanese literature, only 13 cases of intrathoracic paraganglioma or pheochromocytoma is reported. The literature was reviewed.

Adult↗
PubMed1991

Cytogenetic and clonal culture evaluation after response to low dose Ara-C in myelodysplastic syndromes.

Cytogenetic and bone marrow culture studies were performed sequentially in 13 patients with myelodysplastic syndromes (MDS) who responded to low dose cytosine arabinoside (Ara-C) treatment (complete in nine and partial in four patients). Of nine patients with initial clonal karyotypic abnormalities, six recovered a normal karyotype after attaining a response to treatment, but the other three patients retained partial or total karyotypic abnormalities. A new clonal karyotypic abnormality appeared after treatment in one patient. Eight patients showed normal colony growth of both granulocyte-macrophage colony-forming units and erythroid burst-forming units after treatment, but five were still defective. There was a clear difference in the duration of response to treatment between these two groups. Consolidation treatment was not effective in patients with persistent karyotypic abnormalities or defective colony formation. Although the number of patients studied is small, these results suggest that hemopoiesis in patients with MDS following a response to treatment with low dose Ara-C is heterogeneous. Consolidation chemotherapy is recommended to ensure and prolong the response in patients showing normalization of both cytogenetic and bone marrow culture results.

Adolescent↗
PubMed1990

Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma.

The first demonstration of cytokine expression in T-cell lymphoma by immunohistochemical methods is reported. Lymph node biopsy specimens were obtained from 18 patients with peripheral T-cell lymphoma. Interleukin 4 (IL-4) and gamma-interferon were each detected in 7 lymph nodes. Lymph node specimens diagnosed as angioimmunoblastic T-cell lymphoma and angiocentric lymphoma having distinctive histopathological features expressed IL-4 more frequently than other T-cell lymphomas, and all 7 patients expressing IL-4 had hypergammaglobulinemia. Lymph nodes with gamma-interferon expression showed an increase in histiocytes and/or epithelioid cells. Thus, IL-4 may play an important role in the development of hypergammaglobulinemia as well as in the growth and histopathogenesis of T-cell lymphoma, and gamma-interferon may be responsible for the development of Lennert's lesion.

Antibodies↗
PubMed1990

Response of leukemic cells to the sequential combination of GM-CSF and G-CSF.

We designed two experiments using delayed stimulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) with colony-type analysis in order to elucidate the characteristics of factor-dependent proliferation and differentiation of leukemic progenitor cells. Eight patients with acute myelogenous leukemia showing non-autonomous colony growth were selected. Three of the six cases showed that delayed addition of G-CSF to agar culture initiated by GM-CSF had no influence on the type and number of colonies; whereas, delayed addition of GM-CSF to G-CSF resulted in additional GM colonies. These findings were the same for normal bone marrow progenitors. In two cases, granulocytic colonies markedly increased with delayed addition of G-CSF to GM-CSF. Synergism occurred in one case where GM-CSF was used first. In the next experiment, regardless of whether CSF was used during the 48 hour preincubation, subsequent colony types were affected by the CSF used in agar culture. But colony numbers increased 1.5 fold in two of six cases by preincubation with GM-CSF, and 1.2 to 1.7 fold in all normal cases by preincubation with G-CSF. These results suggest that although there is a great heterogeneity in the response to CSF, some leukemic progenitors act like normal progenitors.

Colony-Stimulating Factors↗
PubMed1990

Terminal differentiation of human erythroleukemia cell line K562 induced by aphidicolin.

To analyze the relationship between differentiation and DNA replication, the effect of aphidicolin, a specific inhibitor for DNA polymerase alpha, was measured with respect to erythroid differentiation and activities of DNA polymerases alpha, beta, and gamma. Five micromolar aphidicolin completely blocked the growth of K562 cells and caused 80% of cells to become hemoglobin positive after 5 days exposure. The cessation of K562 cell growth induced by aphidicolin was irreversible, whereas the inhibition of HeLa cell growth was completely reversible. The enzyme activity of DNA polymerase alpha of K562 cells showed a 50-110% increase with aphidicolin treatment as compared to control K562 cells; activities of DNA polymerases beta and gamma were not affected. These features sharply contrasted with the erythroid induction of the same cells by hemin, where cell growth was not suppressed and DNA polymerase alpha was not increased but rather decreased. The enzyme activity of DNA polymerase alpha remained high even after removal of aphidicolin from the culture medium. These results suggest that treatment with aphidicolin might induce an accumulation of protein factors for replication and/or differentiation, causing rapid cell differentiation of cells without cell division.

Antineoplastic Agents↗
PubMed1990

Patchy haemopoiesis in long-term remission of idiopathic aplastic anaemia.

13 patients with idiopathic aplastic anaemia in remission for more than 2 years were examined to define the haemopoietic status by means of bone marrow scintigraphy, ferrokinetics and bone marrow culture for haemopoietic progenitor cells. Haemoglobin levels reached the normal range in all these patients although mild neutropenia and thrombocytopenia were still observed in 5 patients. Bone marrow scintigrams using indium-111 showed normal distribution in 2, diffuse low accumulation in 3, patchy distribution in 7, and expanded distribution with patchy uptake in 1 patient. The defective haemopoiesis was also confirmed by ferrokinetic and bone marrow culture studies. The patchy haemopoiesis appears to characterize the residual marrow damage in remission of idiopathic aplastic anaemia.

Adult↗
PubMed1990

Spontaneous remission of agnogenic myeloid metaplasia in a splenectomized patient: a case report with erythrokinetic studies.

A 67-year-old woman with agnogenic myeloid metaplasia, who underwent splenectomy 1 year after the diagnosis, experienced spontaneous hematologic remission 6 years after splenectomy. Ten months before her anemia improved, peripheral leukocytes no longer showed a shift to the left and peripheral erythroblasts had disappeared. Sequential erythrokinetic studies revealed ineffective erythropoiesis with mild hemolysis and expansion of marrow activity in the tibia and femur but no erythropoiesis in the sacral or vertebral marrow.

Aged↗
PubMed1990

[Chronic cytopenia associated with T8 lymphocytosis successfully treated with glucocorticoids].

We reported a prednisolone effective case of T 8 lymphocytosis. The patient was 83 years old male, who had suffered from hypoplastic anemia for more than 5 years before he admitted to our hospital. His blood picture was peculiar because adding to granulocytopenia, CD8 (+) large granular lymphocytes were dominant among his lymphocytes. A few days after administration of bolus methylprednisolone, prominent reticulocytosis and rapid improvement of anemia occurred and the latter continued for more than 1 year. We performed in vitro study on the mechanism of his cytopenias. The result of Southern blot analysis showed that his blood lymphocytes had a unique rearranged pattern of T cell receptor beta chain gene. Mononuclear cells had an inhibitory effect on autologous and allogenic CFU-E colony formation of bone marrow cells. These facts suggest that colony proliferating CD8 (+) lymphocytes had an inhibitory effect on erythropoiesis in vivo, and prednisolone blocked this inhibitory pathway in this patient.

Aged↗
PubMed1990

[Clinical evaluation of cefbuperazone in severe infections complicated with hematological disorders].

The efficacy and the safety of an antibiotic in cephamycin group, cefbuperazone (CBPZ), were investigated in 93 patients with severe infections complicated with hematological disorders. The efficacy evaluation was made in 85 cases with underlying hematological disorders including 49 cases (57.6%) of leukemia and 18 cases (21.2%) of malignant lymphoma. The overall efficacy rate was 50.6% of the 85 evaluable cases. The clinical efficacy rate for sepsis and suspected sepsis was 53.4%. The most frequently used group of antibiotics for combination therapy was aminoglycosides in 37 cases, in which an efficacy rate of 62.2%, a higher rate than the efficacy rate of 48.5% for all the combination therapy cases, was obtained. In 16 cases in which penicillins were used as combination drug, the efficacy rate obtained was low, 31.3%. Efficacy rates obtained for cases with different neutrophil counts at the start of therapies were as follows: 52.2% in 23 cases with neutrophil counts below 100/mm3, 46.2% in 13 cases with neutrophil counts between 100 and 499/mm3 and 51.3% in 39 cases with neutrophil counts equal to or above 500/mm3, thus no significant differences in efficacy rates were observed for patients with different neutrophil counts. These results appear to suggest that CBPZ, alone or in combination with other antibiotic such as aminoglycosides, may be quite useful in the treatment of severe infections in patients with hematological disorders.

Adolescent↗
PubMed1990

[Difference in the therapeutic efficacy between anaplastic astrocytoma and glioblastoma multiforme types].

We have investigated the differences in therapeutic efficacy between 25 cases with an anaplastic astrocytoma (AA group) and 31 cases with a glioblastoma multiforme (GM group). A good response to induction therapy was achieved with radiation and nitrosourea after a (sub) total removal that led to a prolonged tumor-free interval that was remarkable in the AA group, especially in those with moderate anaplastic astrocytoma. On the other hand, in the GM group, early recurrence tended to occur with no correlation to the degree of the tumor resection, and this made the execution of the maintenance therapy difficult in spite of a similar response to the initial induction therapy as that seen in the AA group.

Adult↗