Biomedical subjects

T Hotta

Publications and source records attributed to T Hotta.

At least 163 records · Page 9Linked to original sources

PubMed1995

Structure of the gene encoding the alpha subunit of the human interleukin 3 receptor.

Interleukin 3 is a cytokine that stimulates proliferation and differentiation of hematopoietic progenitor cells. Its receptor consists of two subunits, an interleukin 3-specific alpha subunit and a beta subunit shared by garanulocyte-macrophage colony stimulating factor and interleukin 5 receptors. In this paper, we determined the genomic structure of the alpha subunit of the human interleukin 3 receptor, which spans approximately 40 kb and has 12 exons. We found that the genomic structures of the alpha subunits of the human interleukin 3 and granulocyte-macrophage colony stimulating factor receptors are very similar. They possess a unique additional intron in the 'C domain', which is absent in the alpha subunit of the interleukin 5 receptor. These results suggest a shared evolutionary pathway of these two genes.

Base Sequence↗

PubMed1995

In vitro differentiation and proliferation in a newly established human rhabdomyosarcoma cell line.

A newly established cell line, designated NRS-1, was derived from an alveolar rhabdomyosarcoma that developed in the left forearm of a 7-year-old girl. The cell line had a t(2; 13) chromosomal translocation. Reverse transcription-polymerase chain reaction demonstrated that 5' PAX3-3' FKHR chimeric transcript was expressed in NRS-1 cells. NRS-1 cells showed myogenic differentiation without any particular stimulus in vitro and exhibited various kinds of muscle markers. All-trans retinoic acid promoted cell differentiation in the myogenic direction. Transforming growth factor-beta (TGF-beta) inhibited myogenic differentiation of those cells and promoted cell proliferation.

Base Sequence↗

PubMed1995

Bone formation in vitro and in nude mice by human osteosarcoma cells.

Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found the alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.

Adolescent↗

PubMed1995

Clear cell chondrosarcomas arising from rare sites.

Three cases are reported of clear cell chondrosarcoma arising from unusual sites: talus, rib and vertebra. Radiographically, two tumors showed osteolytic features and the vertebral tumor showed osteoplastic change. Histologically, all tumors consisted of clear cells that had a centrally placed nucleus surrounded by clear cytoplasm, osteoclast-like giant cells, areas of conventional chondrosarcoma, and various amounts of reactive bone. The tumor in the talus was initially diagnosed as benign chondroblastoma, but it recurred. The rib tumor showed marked cystic formation stimulating aneurysmal bone cyst. The osteoplastic radiographic feature in vertebral tumor was considered to be due to the abundant bone formation.

Adolescent↗

PubMed1995

Choroid plexus carcinoma in the lateral ventricle--case report.

A 68-year-old male presented with choroid plexus carcinoma in the left lateral ventricle manifesting as dysarthria and gait disturbance. Magnetic resonance imaging showed a homogeneously enhanced mass in the trigone of the left lateral ventricle. Selective left posterior cerebral arteriography showed the tumor was fed by the left medial posterior choroidal artery. Detailed examinations found no evidence of an extraneural primary focus. He underwent partial removal of the tumor followed by local Lineac irradiation (50 Gy). After irradiation, the serum level of carcinoembryonic antigen decreased and the size of the residual tumor was reduced.

Adenocarcinoma↗

PubMed1995

[A case of dural arteriovenous malformation in the anterior fossa associated with an occlusion of the unilateral middle cerebral artery with moyamoya phenomenon].

The authors report a case of dural arteriovenous malformation (dAVM) in the anterior fossa that was associated with an occlusion of the unilateral middle cerebral artery with Moyamoya phenomenon. The patient was a 79-year-old man referred to our department with an episode of consciousness disturbance and headache. Computed tomography scan showed intracerebral hematoma in the left frontal lobe, combined with left frontal subdural hematoma and subarachnoid hemorrhage. Angiography revealed dAVM in the left anterior fossa, fed by the bilateral ethmoidal and the bilateral middle meningeal arteries, and draining into the superior and inferior sinuses through the pial veins with vascular sacs. While angiography revealed an occlusion of the right middle cerebral artery (M1 portion) good collaterals via leptomeningeal anastomosis had developed. T1-weighted magnetic resonance (MR) images showed an intracerebral hematoma as a low intensity area, and flow-void areas were indicative of vascular sacs. Time-of-flight MR angiography also clearly showed dAVM in the left anterior fossa. Co-existence of an occlusion of an intracranial major artery and dAVM in this location has not been reported previously and it was speculated that this association had occurred by chance.

Aged↗

PubMed1995

[Two patients with aplastic anemia successfully treated with G-CSF and erythropoietin].

Two patients with severe aplastic anemia received combination therapy consisting of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) by subcutaneous injection. During the first 8 weeks, we administered only G-CSF, but subsequently we administered EPO with G-CSF. Administration of G-CSF caused rapid increase in neutrophil counts in each case. In the first case, a 23-year-old woman, the first sign of improvement of anemia appeared in the 12th week but 50 more weeks elapsed before improvement of platelet count. In the second case, a 59-year-old woman, marked increase of reticulocytes appeared in the 32nd week, and the RBC count become normal in the 46th week. Minor improvement of platelet count was obtained in the 40th week. After 53 weeks of treatment, we stopped administration of G-CSF and EPO, and all of peripheral blood cell counts decreased. Therefore G-CSF and EPO were given to her again, and she showed the same response as first administration. It showed that she was dependent upon G-CSF and EPO. Finally she obtained normalization of all blood cell counts. In both cases, no serious side effects were observed. Combination therapy consisting of G-CSF and EPO may be beneficial for patients with aplastic anemia.

Adult↗

PubMed1994

The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin.

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold higher levels of MDM2 gene expression than that observed in normal B cells. Immunohistochemical analysis confirmed MDM2 overexpression at the cellular protein level. MDM2 gene overexpression was found more frequently in patients with the low-grade type of lymphoma (56.5%) than in those with intermediate-/high-grade types (10.8%) (P = .001). Moreover, MDM2 overexpression was found significantly more frequently in patients at advanced clinical stages. Simultaneous analysis of p53 gene mutation showed that three patients had both MDM2 gene overexpression and p53 gene mutation. The results of the present study suggest that MDM2 gene overexpression may play an important role in the tumorigenicity and/or disease progression of CLL and low-grade lymphomas of B-cell origin.

Adult↗

PubMed1994

Evidence for nonclonal hematopoietic progenitor cell populations in bone marrow of patients with myelodysplastic syndromes.

Clonality of marrow hematopoietic progenitor cells in myelodysplastic syndromes (MDS) was analyzed by X-chromosome inactivation pattern using polymerase chain reaction (PCR). Five female patients were included in this study; two with refractory anemia (RA) and three with RA with excess blasts (RAEB). They were heterozygous for BstXI restriction fragment length polymorphisms (RFLP) of the X-chromosome-linked phosphoglycerate kinase (PGK) gene. In each patient, erythroid and nonerythroid colonies, grown in the presence of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibited no remarkable difference in clonal constitution. Two patients showed only one methylation pattern, suggesting the monoclonal origin of hematopoietic progenitor cells. Colonies of two other patients exhibited predominant and minor methylation patterns in PGK gene, indicating that nonclonal progenitor cells remain a minor population. The bone marrow of one patient appeared to contain a greater proportion of nonclonal progenitors. Stem cell factor (SCF), a potent colony-stimulating factor, enhanced both erythroid and nonerythroid colony formation. However, it did not notably alter the clonal constitutions. We conclude that nonclonal hematopoietic progenitor cells can persist in a substantial number of MDS patients.

Aged↗

PubMed1994

Peripheral blood cells are predominantly chimeric of affected and normal cells in patients with paroxysmal nocturnal hemoglobinuria: simultaneous investigation on clonality and expression of glycophosphatidylinositol-anchored proteins.

To investigate clonal compositions of hematologic cells in paroxysmal nocturnal hemoglobinuria (PNH), we analyzed peripheral blood (PB) cells of 12 female patients with PNH, by clonality analysis using X-chromosome inactivation and assessment of expression of glycophosphatidylinositol-anchored proteins (GPI-APs) by flow cytometry. Southern hybridization showed that granulocytes were monoclonal in three and polyclonal in eight patients, respectively, whereas lymphocytes were polyclonal in all nine patients examined. Expressions of CD16 and CD59 on granulocytes varied greatly in seven patients examined. Clonality analysis of granulocytes by the polymerase chain reaction showed that CD59- and CD59low+ cells were monoclonal, whereas CD59+ cells were polyclonal. It was shown that PB cells are predominantly chimeric of clonal (GPI-AP- or GPI-APlow+) and nonclonal (GPI-AP+) cells in PNH, and that degrees of chimerism differ greatly from patient to patient.

Adolescent↗

PubMed1994

O6-alkylguanine-DNA alkyltransferase activity of human malignant glioma and its clinical implications.

Activity of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) is an important determinant of responsiveness of tumor cells to chloroethylnitrosoureas (CENUs), representative chemotherapeutic agents for primary malignant gliomas. In order to assess the real states of this repair protein in human malignant gliomas, we assayed AGT activity in surgically extirpated 42 malignant glioma samples and studied the distribution of the activity under certain clinical conditions. There were wide variations in AGT activity between individuals. No significant difference in AGT activity on average was seen either between glioblastoma and anaplastic astrocytoma, nor between primary and recurrent tumors. Among 42 malignant gliomas, 7 samples (16.7%) had low AGT activity less than 0.1 pmoles/mg protein. In the case of glioblastoma, tumors possessing higher AGT activity tended to be less responsive to post-operation remission-induction therapy including CENUs. The result of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) chemosensitivity assay by using the corresponding surgical specimens suggested a close relationship between cellular resistance to CENUs and AGT activity. It was found to be unlikely that a short term administration of CENUs had a significant effect on AGT activity of brain tumors in human body. We could detect a bit of definite evidences of the relevance of AGT to resistance to CENUs and need to conduct further investigations for other resistance factors.

Astrocytoma↗

PubMed1994

In vivo effects of recombinant human lymphotoxin on human medulloblastoma xenograft: enhancement of antitumor activity of etoposide.

The authors investigated the antitumor activities of rHuLT alone and in combination with etoposide on human meduloblastoma xenografts growing subcutaneously in nude mice. Intravenous administration of rHuLT (1.0 x 10(5) U/kg, 5.0 x 10(5)U/kg, 2.5 x 10(6)U/kg, three times a week for three weeks) suppressed medulloblastoma growth depending on the dose. However, the highest dosage caused serious side effects. Combining rHuLT (intravenously, 5.0 x 10(5)U/kg, three times a week for three weeks) with etoposide (intraperitoneally, 20mg/kg, once a week for three weeks) increased the antitumor activity without causing serious toxicity. Microscopically, tumor specimen showed thrombosed tumor vessels and massive necrosis 3 weeks after rHuLT treatment. Ultrastructural examination revealed that 120 minutes after the administration of rHuLT alone, disruption of interendothelial junctions was evident, and that the endothelial cells were destroyed at 240 minutes. Concentration of etoposide in tumor tissue peaked 30 minutes after intraperitoneal administration, and then decreased with time. When etoposide was administered in combination with rHuLT, the concentration of etoposide in tumor tissue after 60 to 240 minutes was significantly higher than when etoposide was given alone, and the area under the concentration versus time curve was also greater for the tumors of mice with combination treatment. The findings suggest that the proper combination of rHuLT and etoposide may have synergistic antitumor activities. Histological changes suggest that increased concentrations of etoposide within the tumor after combination therapy may occur due to increased vascular permeability and/or decreased etoposide clearance which is the result of blood statis in the tumor vasculature.

Animals↗

PubMed1994

Neural tissue-related proteins (NSE, G0 alpha, 28-kDa calbindin-D, S100b and CK-BB) in serum and cerebrospinal fluid after cardiac arrest.

To estimate brain damage after cardiac arrest, the concentrations of neuron specific enolase (NSE), GTP-binding protein (G0 alpha), 28 kDa calbindin-D, S100b protein, and creatine kinase BB (CK-BB) in serum and cerebrospinal fluid (CSF) were determined by enzyme immunoassays. Ten mongrel dogs were subjected to 30 min of circulatory arrest at normal body temperature and serial CSF and blood samples were taken during the first 18 h after reperfusion. The NSE concentration in CSF increased significantly after reperfusion, reaching a 15-fold increase (243 +/- 107 ng/ml, p < 0.01) 18 h later, however, it did not increased significantly in serum (8.1 +/- 3.3 ng/ml vs. 23.5 +/- 7.0 ng/ml). G0 alpha concentration in CSF increased sharply between the 2nd and 4th h after reperfusion and peaked 18 h after reperfusion (428 +/- 195 pg/ml, p < 0.01), however, it did not increase significantly in serum. Calbindin-D concentration in CSF increased between the 1st and 6th h after reperfusion, and reached a plateau thereafter (621 +/- 235 ng/ml, a 23-fold increase, p < 0.05) and also increased significantly in serum (p < 0.05). The S100b concentration in CSF also increased dramatically after the 4th h of reperfusion and reached a plateau at the 8th h after reperfusion (16.0 +/- 9.3 ng/ml, a 50-fold increase, p < 0.01), however, it in serum was below the detection threshold. The CK-BB concentration in CSF peaked 4 h after reperfusion (113 +/- 69 ng/ml, a 19-fold increase, p < 0.01) and it in serum increased 4-fold (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Estimation of triggering work of breathing. The dependence on lung mechanics and bias flow during pressure support ventilation.

Work of breathing necessary to trigger a ventilator (WOBtr) was calculated during pressure support ventilation (PSV), and the effect of bias flow on WOBtr was evaluated. A spring-loaded bellows type lung model with two bellows placed in series was used to simulate spontaneous breathing. A Venturi mechanism of jet flow generated subatmospheric pressure inside the diaphragm bellows simulated inspiratory effort. The lung compliance (CL) was set at 0.3 L/cm H2O or 0.05 L/cm H2O. The airway resistance (Raw) was set at 5, 20, or 50 cm H2O/L/s. Pressure support levels were increased from 0 to 45 cm H2O. Sensitivity was set at 2 cm H2O. No bias flow was used at first. The WOBtr was calculated using a pressure-volume (P-V) loop derived from the diaphragm bellows movement during the triggering period. We determined WOBtr and its dependence on the various pressure support (PS) levels, CL and Raw. To evaluate the effects of bias flow on WOBtr and triggering delay, a ventilator was put in the PSV mode, with various bias flow rates (from 0 to 20 L/min) at a sensitivity of 2 cm H2O. We found that when no bias flow was used, WOBtr increased with an increase in both Raw and end-expiratory lung bellows pressure which was considered as auto-PEEP. With bias flow, both triggering delay and WOBtr increased. An increase in bias flow at a given PS level resulted in both decreased pressure support time and tidal volume (VT). It is concluded that the bias flow system is not desirable for use during PSV.

Airway Resistance↗

PubMed1994

Tumor necrosis factor-beta gene expression and its relationship to the clinical features and histopathogenesis of peripheral T-cell lymphomas.

We investigated the levels of tumor necrosis factor-beta (TNF-beta) mRNA in the tumorous tissues of a series of 18 patients with peripheral T-cell lymphomas (PTCL), to assess the contribution of the expression of this gene to the features of the disease. Total RNA, extracted from diagnostic tissue specimens, was subjected to semiquantitative analysis by reverse transcription-coupled polymerase chain reaction (RT-PCR). The level of TNF-beta mRNA was semiquantified against that in MT-2 cells, a line of human T cells infected with human T cell leukemia virus type I (HTLV-I). Expression of TNF-beta in neoplastic T-cells was confirmed by immunohistochemistry. The extent of TNF-beta gene expression was correlated with the histopathological features of neovascularization. There was also a relationship between the extent of TNF-beta gene expression and the presence of B-symptoms. Results suggest that TNF-beta produced by neoplastic T-cells influences clinical features and is involved in histopathogenesis of PTCL.

Female↗

PubMed1994

Growth analysis of marrow CD34-positive hematopoietic progenitor cells in patients with myelodysplastic syndromes.

The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from 25 patients with myelodysplastic syndromes (MDS) were studied. In all patients this purified cell population showed erythroid (burst-forming unit erythroid; BFU-E) or non-erythroid colony growth, both of which were more restricted than non-purified mononuclear cell population under stimulation with erythropoietin (EPO) or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients examined were put into two groups; refractory anemia (RA) or RA with ringed sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t exhibited a similarity to the cells of normal individuals in their responsiveness to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF caused powerful but highly variable responses in both erythroid and nonerythroid colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally stimulated with early-acting hematopoietic growth factors including IL-6, IL-3 and SCF in a fashion similar to those of normal individuals.

Adult↗

PubMed1994

Effects of stem cell factor (SCF) on human marrow neutrophil, neutrophil/macrophage mixed, macrophage and eosinophil progenitor cell growth.

The effects of stem cell factor (SCF) on the subpopulations of granulocyte/macrophage colony-forming units (CFU-GM) were examined. Hematopoietic progenitor cells were enriched from normal adult bone marrow specimens by immunomagnetic beads using an anti-CD34 antibody and lineage marker antibodies for positive selection and negative selection, respectively. SCF enabled neutrophil and neutrophil/macrophage mixed progenitors to respond to granulocyte/macrophage colony-stimulating factor (GM-CSF) or interleukin 3 (IL-3) and to develop the colony and further cluster formation. The neutrophil colonies stimulated by GM-CSF or IL-3 consisted mainly of immature cells, while the colonies stimulated by granulocyte colony-stimulating factor (G-CSF) consisted of mature neutrophils irrespective of the addition of SCF. In macrophage and eosinophil lineages, SCF augmented the colony formation in the presence of GM-CSF or IL-3, whereas the enhancement of total progenitor cell growth (colonies plus clusters) was not so marked as compared with the neutrophil lineage. Time-course observation revealed that SCF could stimulate macrophage and eosinophil progenitors to form colonies rapidly. These findings indicate that SCF acts on late myeloid progenitor cells in manners different from the lineages of commitment.

Adult↗

PubMed1994

[A comparative clinical study on flucytosine alone and in combination with fluconazole in hematological malignancies: a multicenter study using the envelope method].

Two different flucytosine (5-FC) treatment regimens, one by itself and the other in combination with fluconazole (FLCZ) were compared in chemotherapy against mycotic infections in 60 patients with hematological diseases. The patients in a randomized fashion were assigned to the two treatments. In the combination regimen, the two drugs were used in half doses. beta-D-Glucan and D-arabinitol in the sera of patients were measured to document mycotic infections, and bacterial examinations were also performed. The efficacy of the combination therapy was 60.0% (18/30) and that of 5-FC alone was 65.5% (19/29). The stratified evaluation indicated that no factor was found to contribute to the efficacy in the two treatments with statistical significance. The side effects occurred in few cases and none of those was serious; including, one case of subjective symptom in each groups and two episodes of liver dysfunction in combination treatment. Changes in beta-D-glucan concentrations in the sera reflected well the pathophysiology of mycotic infections and clinical improvement. These results suggested that a combination of 5-FC and FLCZ at half doses provided a clinical benefit comparable to 5-FC alone at the ordinary dose, and the safety was considered satisfactory.

Adult↗