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Biomedical subjects

K Usuki

Publications and source records attributed to K Usuki.

At least 55 records · Page 3Linked to original sources
PubMed1995

Granulocyte colony-stimulating factor in acute myeloid leukemia.

The clinical application of recombinant human G-CSF in patients with acute myeloid leukemia (AML) has been controversial because it stimulates the in vitro proliferation of leukemic cells. In order to explore the possibility of predicting in vivo leukemic proliferation after G-CSF administration to AML patients by using in vitro assays, we investigated the leukemic blasts of 30 AML patients, including 14 patients who received G-CSF for severe infection associated with neutropenia following chemotherapy (G-CSF group) and 16 patients who did not (control group). Of the 14 patients in the G-CSF group, 9 showed an increase of leukemic blasts in the peripheral blood during G-CSF administration, while 11 of the 16 control patients developed leukemic resurgence. In the G-CSF group, the frequency of leukemic resurgence among patients whose blasts showed dose-dependent proliferation after addition of G-CSF to cultures was similar to that among patients whose blasts did not. In addition, there were no significant differences between the G-CSF and control groups in [3H]thymidine incorporation by leukemic cells and leukemic colony formation after the addition of G-CSF to cultures. The G-CSF receptor affinity of leukemic blasts was significantly higher in the patients with leukemic resurgence (mean dissociation constant [Kd]: 55 pM in the G-CSF group and 63 pM in the control group) than in those without it (101 pM and 96 pM, respectively), and the number of G-CSF receptors per cell was significantly lower when leukemic resurgence occurred (200 in the G-CSF group and 260 in the control group) than when it did not (3400 and 3030, respectively). Immunophenotyping (for CD2, CD7, CD10, CD13, CD19, CD33, CD34, CD71, HLA-DR, glycophorin A and the G-CSF receptor) revealed no significant differences between blasts from the patients with and without leukemic resurgence in the G-CSF group. Thus, we conclude that the in vivo leukemic resurgence during G-CSF administration after chemotherapy for AML was not correlated with the in vitro responsiveness of leukemic blasts to this cytokine or with blast phenotyping data. Leukemic resurgence is likely to occur in patients whose leukemic blasts have fewer numbers of G-CSF receptors with a high affinity irrespective of whether patients receive G-CSF.

Acute Disease↗
PubMed1995

Hypereosinophilic syndrome in Hodgkin's disease with increased granulocyte-macrophage colony-stimulating factor.

We report a patient with eosinophilia accompanied by Hodgkin's disease who showed remarkable increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) in plasma but no increase in interleukin-5 (IL-5). The plasma GM-CSF level normalized as eosinophilia and lymphadenopathy disappeared after chemotherapy. Immunohistochemical study with immunoperoxidase staining technique showed a positive stain in lymph node cells by monoclonal anti-GM-CSF antibody. Eosinophilia is often accompanied by Hodgkin's disease, and several cases have been reported to show high levels of plasma IL-5. To our knowledge, this is the first report to show a high level of plasma GM-CSF in Hodgkin's disease with eosinophilia.

Aged↗
PubMed1995

Combination therapy with granulocyte colony-stimulating factor, all-trans retinoic acid, and low-dose cytotoxic drugs for acute myelogenous leukemia.

A 67-year-old man presented with acute myelogenous leukemia (M2). Peripheral blood examination revealed a leukocyte count of 1,700/mu l with 1% myeloblasts, and bone marrow aspiration showed 42.6% myeloblasts with Auer bodies. Culture of his marrow cells at diagnosis showed that granulocyte colony-stimulating factor (G-CSF) promoted cell proliferation, while all-trans retinoic acid (ATRA) inhibited the proliferative effect of G-CSF and induced differentiation. Combination therapy with G-CSF, ATRA, and low-dose cytotoxic drugs achieved complete remission without severe marrow suppression.

Aged↗
PubMed1994

Structural properties of 3.0 kb and 3.2 kb transcripts encoding platelet-derived endothelial cell growth factor/thymidine phosphorylase in A431 cells.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is a 90 kDa protein consisting of two non-covalently associated subunits. In addition to the previously identified 1.8 kilobase (kb) PD-ECGF/TP mRNA, the human epidermoid carcinoma cell line A431 was found to express 3.0 kb and 3.2 kb transcripts. cDNA cloning of the larger transcripts revealed that they contain long 5' leader sequences of 1.5 kb and 1.7 kb, respectively, and the same open reading frame encoding PD-ECGF/TP as that of the 1.8 kb transcript. Comparison with the published PD-ECGF/TP genomic sequence shows that the long 5' leader sequence contain 7 of 8 copies of Sp-1 binding sites present in the transcription promoter region of the 1.8 kb transcript.

Base Sequence↗
PubMed1994

[Hypoplastic leukemia successfully treated by oral administration with cytarabine ocfosfate].

A 73-year-old man was admitted to our hospital with pancytopenia in December, 1992. The data of his peripheral blood were as follows: WBC 1,100/microliters (stab 9.0, seg 11.5, eosin 3.5, mono 1.0, lymph 75.0), RBC 176 x 10(4)/microliters, Hb 6.6 g/dl, platelet 4.6 x 10(4)/microliters. Bone Marrow was hypocellular (cell count 1.4 x 10(4)/microliters) and consisted of 30% blasts (peroxidase positive). He was diagnosed as having hypoplastic leukemia. Oral administration of cytarabine ocfosfate (50 mg/day) was begun from the 5th of January, 1993. The dose of cytarabine ocfosfate was increased to 100 mg/day since the 13th of January, 1993, and he was discharged from the hospital on the 23rd of January, 1993. Since then, he has been treated with cytarabine ocfosfate alone in the outpatient clinic. Pancytopenia began to improve in one month, and the data on the 7th of May, 1993 were as follows: WBC 3,500/microliters (stab 2.0, seg 37.5, eosin 1.5, baso 1.0, mono 16.5, lymph 41.5), RBC 249 x 10(4)/microliters, Hb 10.4 g/dl, platelet 15.4 x 10(4)/microliters. Bone marrow became normocellular (cell count 22.0 x 10(4)/microliters) and blasts decreased to 3.0%, and complete remission was confirmed. There were no adverse effects.

Administration, Oral↗
PubMed1993

Differential expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human lung carcinoma cell lines.

In the present investigation we have studied the expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) in ten different human lung carcinoma cell lines, four small cell carcinomas and six non-small cell carcinomas. None of the small-cell lung carcinoma cell lines demonstrated expression of PD-ECGF/TP mRNA. However, four of six of the non-small cell carcinoma cell lines expressed the 1.8 kb PD-ECGF/TP transcript. The cell lines derived from the single squamous cell carcinoma and the two adenocarcinomas expressed the PD-ECGF/TP mRNA, and were found to have the corresponding protein both in cell lysates and conditioned media as determined both by immunoblotting and measurement of thymidine phosphorylase activity. Only one of three studied large cell carcinoma cell lines expressed low levels of PD-ECGF/TP mRNA, but the corresponding PD-ECGF/TP protein was not demonstrated by immunoblotting.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Platelet-derived endothelial cell growth factor. Pharmacokinetics, organ distribution and degradation after intravenous administration in rats.

Platelet-derived endothelial cell growth factor (PD-ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD-ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD-ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [125I]PD-ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half-lives of 17 min and 7 h, respectively. PD-ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half-life in the circulation, together with the specificity for endothelial cells, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine.

Animals↗
PubMed1992

Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity.

Platelet-derived endothelial cell growth factor (PD-ECGF), a protein which stimulates angiogenesis in vivo, is shown to have a 39.2% amino acid sequence similarity over a 439 amino acid region with the thymidine phosphorylase of Escherichia coli (E. coli). Using recombinant human PD-ECGF, we show that PD-ECGF has thymidine phosphorylase activity. Analysis by gel chromatography revealed that recombinant human PD-ECGF occurs as a 90 kDa homodimer, similar to other thymidine phosphorylases. In addition to a possible effect on DNA synthesis, PD-ECGF was shown to affect [3H]thymidine assays in a manner which is not related to cell proliferation. The in vitro and in vivo effects of PD-ECGF may thus occur by an indirect mechanism through its enzymatic activity.

Amino Acid Sequence↗
PubMed1991

Covalent linkage between nucleotides and platelet-derived endothelial cell growth factor.

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa peptide mitogen which is present in platelets and placenta and produced by certain cultured cell lines. Immunoprecipitation of A431 cells metabolically labeled with [32P]orthophosphate revealed the incorporation of 32P radioactivity into PD-ECGF. Phosphoamino acid analysis showed that serine residues of PD-ECGF were phosphorylated in vivo. Forskolin, 12-O-tetradecanoylphorbol-13-acetate, and epidermal growth factor had no effect on the in vivo phosphorylation of PD-ECGF. Moreover, incubation of pure PD-ECGF with [gamma-32P]ATP led to labeling of PD-ECGF. Optimal labeling was achieved by incubation at 95 degrees C for 5 min in the presence of sodium dodecyl sulfate, dithiothreitol, and Mg2+ or Mn2+. PD-ECGF was also labeled with [2,8-3H]ATP, [2,5',8-3H]ATP, or [alpha-32P]ATP. ATP and GTP were the preferred nucleotide substrates by comparison with other nucleotides and related components. Partial amino acid hydrolysis liberated a significant amount of O-[32P]phosphoserine from PD-ECGF labeled in vitro with [gamma-32P] ATP. Furthermore, 32P-radiolabeled nucleotides were released after snake venom phosphodiesterase or piperidine treatment from PD-ECGF labeled in vitro with [alpha-32P]ATP or [gamma-32P]ATP, as well as from PD-ECGF labeled in vivo with [32P]orthophosphate. These data indicate that serine residues of PD-ECGF can be covalently linked to phosphate groups of nucleotides, resulting in a nucleotidylated protein. The functional significance of this post-translational modification remains to be determined.

Adenosine Triphosphate↗
PubMed1991

Platelet-derived endothelial cell growth factor.

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45 kDa single chain polypeptide which stimulates endothelial cell growth and chemotaxis in vitro and angiogenesis in vivo. Analysis of a full length PD-ECGF cDNA revealed an open reading frame coding for 482 amino acids without homology to other known proteins. No signal sequence was observed, and analysis of the biosynthesis and processing of PD-ECGF in a thyroid carcinoma cell line revealed that PD-ECGF is released only very slowly. PD-ECGF becomes covalently associated with nucleotide triphosphates (e.g., ATP) in vivo, as well as in vitro. The physiological significance of this posttranslational modification remains to be elucidated. The tissue distribution and target cell specificity of PD-ECGF suggest roles in angiogenesis (e.g., during wound healing and in the developing placenta), as well as in the maintenance of the integrity of the endothelial cell lining of large vessels.

Endothelium, Vascular↗
PubMed1991

Platelet-derived endothelial cell growth factor.

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45 kDa single chain polypeptide, which stimulates the DNA synthesis and chemotaxis of endothelial cells in vitro and angiogenesis in vivo. Purification from human platelets and cDNA cloning from a human placental cDNA library, revealed that PD-ECGF is a novel type of peptide without sequence similarity to hitherto known proteins. PD-ECGF is present in human platelets and placenta, and is produced by certain normal and transformed cultured cells; it lacks a hydrophobic leader sequence and most of the protein remains inside the producer cells. Analysis of PD-ECGF produced by cultured cells, revealed that it contains nucleotide(s) covalently bound to serine residues. The in vivo function of PD-ECGF is not known; its target cell specificity and tissue distribution suggest roles in angiogenesis of the placenta and in the maintenance of the integrity of the endothelial cell layer of blood vessels. PD-ECGF may have a clinical utility in the stimulation of wound healing and re-endothelialization of vessels.

Amino Acid Sequence↗
PubMed1990

Localization of platelet-derived endothelial cell growth factor in human placenta and purification of an alternatively processed form.

Platelet-derived endothelial cell growth factor (PD-ECGF) was purified to homogeneity from human term placenta, an organ characterized by extensive angiogenesis. N-terminal amino acid sequencing revealed that placental PD-ECGF was proteolytically processed at Thr-6, in contrast to PD-ECGF purified from human platelets, which is processed at Ala-11. The purified factor stimulated porcine aortic endothelial cells as well as two choriocarcinoma cell lines. Immunohistochemical staining revealed that PD-ECGF was present in the connective tissue cells of the placenta. The possibility that PD-ECGF is involved in the development of the placenta is discussed.

Amino Acid Sequence↗
PubMed1989

Production of platelet-derived endothelial cell growth factor by normal and transformed human cells in culture.

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45-kDa endothelial cell mitogen which has angiogenic properties in vivo. We report here that human foreskin fibroblasts, a human squamous cell carcinoma cell line, and 2 out of the 3 human thyroid carcinoma cell lines investigated produce PD-ECGF, whereas 21 other cell lines examined do not. The positive cell lines contained a 1.8-kilobase PD-ECGF mRNA, and a 45-kDa protein could be demonstrated in lysates of the cell lines by immunoblotting and immunoprecipitation using a specific antiserum against PD-ECGF. Furthermore, the cell lysates contained mitogenic activity for endothelial cells that was neutralized by the PD-ECGF antiserum. PD-ECGF was found to be secreted only slowly from the producer cells, consistent with the previous finding that the primary translation product lacks a signal sequence. The restricted expression and intracellular sequestration of PD-ECGF imply a strictly controlled function in endothelial cell proliferation and angiogenesis. Aberrant production of PD-ECGF may play a role in tumor angiogenesis.

Animals↗
PubMed1988

Rhabdomyosarcoma with bone marrow metastasis simulating acute leukemia. Report of two cases.

Rhabdomyosarcoma manifested as a systemic disease is very rare and cases showing diffuse metastasis in the bone marrow are most unusual. Recently we encountered two cases of rhabdomyosarcoma with diffuse bone marrow metastasis which were clinically manifested as acute leukemia. The first patient was a 15-year-old female, who was admitted in 1982 with pancytopenia and many large primitive cells in bone marrow aspirates, hematological malignancy being diagnosed. Thereafter the bilateral breasts showed rapid swelling and a biopsy specimen revealed the histological features of typical alveolar rhabdomyosarcoma. The primary site of the neoplasm remained undetermined during the course. At autopsy, it was disclosed that the neoplasm originated from the left thigh and showed generalized metastasis. The second patient was a 38-year-old man, who was admitted in 1986 because of a nasal polyp obstructing the nasal cavity, and persistent nasal bleeding. Peripheral blood samples showed leukoerythroblastosis and thrombocytopenia, and large primitive cells were found in bone marrow aspirates, so that hematological malignancy was initially diagnosed. A biopsy specimen of the nasal polyp showed proliferation of large round cells and electron microscopy demonstrated the ultrastructural features of rhabdomyosarcoma.

Acute Disease↗