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Biomedical subjects

S Okamura

Publications and source records attributed to S Okamura.

At least 217 records · Page 12Linked to original sources

[Evaluation of magnetic resonance imaging in the diagnosis of extension in uterine cervical cancer cases with special attention to imaging planes].

To prove the usefulness of Magnetic Resonance Imaging (MRI) in determining the invasion of uterine cervical cancer with imaging planes, we evaluated 44 patients with histologically proved cervical cancer. MRI was performed with a Signa 1.5 T (General Electric), and a T2-weighted image was used. In coronal planes, the accuracy was 75.0% for parametrial invasion. It was impossible to diagnose in 77.8%, 92.1% and 63.2% the invasion of the uterine body, bladder and rectum, respectively. In axial planes, the accuracy was 76.3%, 92.1% and 78.9% for the invasion of parametrium, bladder and rectum, respectively. It was impossible to diagnose in 72.2% the invasion of the uterine body. In sagittal planes, the accuracy was 80.6%, 97.4% and 89.7% for invasion of the uterine body, bladder and rectum, respectively. In all 39 cases it was impossible to diagnose parametrial invasion. In five cases, MRI failed to detect the tumor in any of the three planes, but in three cases it was able to detect the tumor in at least one of the three. We conclude as follows: 1) MRI is a useful method in determining the invasion of cervical cancer. 2) Coronal planes are recommended for the determination of parametrial invasion, axial planes for the parametrium, bladder and rectum, and sagittal planes for the uterine body, bladder and rectum. 3) All three planes are needed to determine cervical cancer.

Adenocarcinoma↗

Molecular cloning of the cDNA coding for proline-rich protein (PRP): identity of PRP as C4b-binding protein.

Proline-rich protein (PRP) is a plasma protein with a high proportion of proline residues and possessing lipid-binding properties. In order to clarify its structure, a human liver cDNA library was screened using anti-PRP antiserum. Several overlapping phage cDNA clones were isolated and the total nucleotide sequence of the cDNA, 2178 bp in length, was analyzed. The amino acid composition of PRP deduced from the cDNA was essentially the same as that reported for PRP. In a homology search, the cDNA sequence was almost completely the same as the previously reported cDNA sequence of C4b-binding protein. Furthermore, the reported molecular weights of the two proteins under both reduced and unreduced conditions were quite alike. These findings indicate that PRP is identical with C4bp.

Amino Acid Sequence↗

Effect of granulocyte-macrophage colony-stimulating factor on chemiluminescence of human neutrophils.

We investigated the capacity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to enhance the function of neutrophils. Neutrophil function was measured in terms of N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced luminol-dependent chemiluminescence (LDCL). LDCL of fMLP-stimulated neutrophils was enhanced up to 4.5 fold following preincubation with rhGM-CSF. This enhancement depended on the length of preincubation, reaching an optimal level at 120 min. The dose-response relationship for fMLP-induced LDCL of neutrophils preincubated with rhGM-CSF revealed that half-maximum enhancement was achieved at an approximately 20-fold higher concentration than that of colony-forming units in culture-derived colony formation. These results suggest that differences in dose dependency may be explained by differences in the distribution of receptor(s) for GM-CSF. This may also enable GM-CSF to affect the hematopoietic system, which contains cells at various levels of differentiation, thus mediating the host-defense mechanism.

Bone Marrow↗

Measurement of human G-CSF by enzyme-linked immunosorbent assay using monoclonal antibody.

An IgG monoclonal antibody to recombinant human granulocyte colony-stimulating factor (G-CSF), designated HG1, was produced by fusion of immune mouse splenocytes with HAT-sensitive murine myeloma cells. This HG1 was capable of neutralizing the colony-stimulating activity of G-CSF in vitro, and it did not cross-react with human granulocyte/macrophage colony-stimulating factor (GM-CSF). An enzyme-linked immunosorbent assay (ELISA) for measurement of G-CSF was developed using HG1 and a polyclonal antibody against G-CSF raised in a rabbit. The data indicated that the ELISA was highly efficient and sensitive for the detection of as little as 50 pg/ml of recombinant G-CSF. This assay system therefore warrants further attention.

Antibodies, Monoclonal↗

Measurement of human granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay.

An IgG monoclonal antibody against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), designated HGM1, was produced by fusion of immune mouse splenocytes with HAT-sensitive murine myeloma cells. A sandwich enzyme-linked immunosorbent assay (ELISA) for measurement of human GM-CSF was developed using this HGM1 and a polyclonal antibody against GM-CSF raised in a rabbit. GM-CSF in culture supernatants of phytohemagglutinin (PHA)- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) were measured by this ELISA system and the conventional CFU-GM colony formation method. The data indicated that the ELISA was highly efficient and sensitive for the detection of as little as 50 pg/ml recombinant GM-CSF. The CFU-GM colony assay may be influenced by other cytokines which can enhance or suppress colony formation, and ELISA for GM-CSF is more useful for kinetic studies of precise levels of production from PBMC.

Animals↗

Leukoencephalopathy following treatment with carmofur: a case report and review of the Japanese literature.

A 53-year-old woman was treated with 5 courses of CAP treatment following operation for FIGO Stage Ia cancer of the ovary in September 1986. And in April 1987, she started an oral adjuvant chemotherapy with 400 mg/day of carmofur. In early June, she developed vertigo and dysarthia and was hospitalized. A CT scan showed low-density areas adjacent to both lateral ventricles, and an EEG revealed abnormally slow waves. She improved gradually after carmofur was discontinued and left the hospital in October 1987. There have been 24 reported cases of leukoencephalopathy because of carmofur in Japan, but the pathophysiological mechanism involved is not known. Since it is more common in women than in men, its incidence will probably increase in gynecological patients. Therefore, we must be on the lookout for central nervous system signs and symptoms in patients receiving adjuvant chemotherapy with carmofur.

Antineoplastic Agents↗

Protective effect of recombinant murine granulocyte-macrophage colony-stimulating factor against Pseudomonas aeruginosa infection in leukocytopenic mice.

The effects of recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) against Pseudomonas aeruginosa infection in ICR mice were investigated. Mice were treated with cyclophosphamide (CPA) and were then injected intraperitoneally with rmGM-CSF three times daily, beginning on the day after CPA treatment, for 7 days. The number of peripheral blood leukocytes in both CPA- and rmGM-CSF-treated mice and control CPA-treated mice reached a nadir on day 4, when P. aeruginosa was injected intraperitoneally. The administration of rmGM-CSF significantly increased the proportion of survivors among mice infected with a lethal dose of P. aeruginosa. This effect was further analyzed by monitoring sequential changes in leukocyte count and bacterial growth in various organs. The number of bacteria in the peritoneal cavities, peripheral blood samples, and livers of GM-CSF-treated mice decreased to an undetectable level after a transient increase, and the number was significantly lower than that in control mice. In GM-CSF-treated mice, the neutrophil levels in peripheral blood started to increase 5 days after CPA administration and were consistently higher than those in controls. Furthermore, the neutrophils in GM-CSF-treated mice were more mature morphologically. Thus, the prophylactic effect of rmGM-CSF against P. aeruginosa infection may result from a rapid recovery of myelopoiesis and a partial enhancement of mature neutrophil function.

Animals↗

Development of drug resistance in cultured clonogenic leukemic blast cells during the clinical course of myeloblastic leukemia.

We studied changes in the drug sensitivity of clonogenic leukemic blast cells from patients with acute myeloblastic leukemia during clinical courses. These cells were assayed using the colony formation technique in methylcellulose culture. Various doses of each of two chemotherapeutic agents, daunorubicin and aclarubicin, were added at the start of culture, and drug sensitivities were measured in terms of percentage inhibition of leukemic blast colony formation. Clonogenic leukemic blast cells became less sensitive to the drugs which were administered to the patients during the course of the disease, suggesting that development of drug resistance in vivo may reflect the presence of dominant resistant populations of clonogenic leukemic blast cells in vitro.

Aclarubicin↗

[Effect of medroxyprogesterone acetate on side effects of CAP therapy in gynecological malignant tumors].

We concomitantly administered a large dose of medroxyprogesterone acetate (MPA) to gynecological malignant tumor patients undergoing CAP therapy (CAP). Hematological changes in the peripheral blood were compared between concomitant MPA patients and those not receiving MPA to examine the effect of MPA in reducing the marrow depression which is the major side effect of CAP. 1) Leukocyte count reached minimum at the second week of CAP in both groups. There was no significant difference in the count between the two groups. At the third week of CAP, the count improved to 84% of the pre-CAP level in patients receiving MPA and to 68% in those not receiving MPA, a significant difference (p less than 0.01). At the fourth week, leukocyte counts were 105% and 96% of pre-CAP levels, respectively. There was no difference between the two groups, but the leukocyte count returned to the pre-CAP level in the patients receiving MPA. 2) Platelet count showed changes similar to those in the leukocyte count. In patients receiving MPA, the count improved more rapidly within three weeks (118%, p less than 0.01), and was significantly higher at the fourth week (107%, p less than 0.05) than in patients not receiving MPA. 3) Reticulocyte count reached minimum in the first week, thereafter improving rapidly in both groups. No differences were noted between the two groups. 4) The periods needed for one course of CAP were 27.7 +/- 3.3 days in the patients receiving MPA and 29.5 +/- 3.7 days in the patients not receiving MPA, making for a significant difference between the two groups (p less than 0.05). These results show that MPA accelerates recovery from marrow depression caused by CAP. It is anticipated, therefore, that MPA will be helpful in the application of various chemotherapies which are expected to be frequently conducted in the future.

Antineoplastic Combined Chemotherapy Protocols↗

[In vitro studies of 5-FU sensitivity on uterine cervical cancer cell lines--comparison between squamous cell carcinoma and adenocarcinoma].

In order to improve the postoperative survival rate of patients with cervical cancer, we have treated them with adjuvant chemotherapy (oral Tegafur) and proved this treatment to be useful. However, the prognosis of cervical adenocarcinoma cases has not been improved yet. In this study, 5-FU sensitivity, morphological changes and DNA metabolism of cultured cervical cancer cells were examined using OMC-1 and OMC-4 cell line originating from cervical squamous cell carcinoma and adenocarcinoma, respectively. The EC 50 (Effective Concentration for 50% Cell Kill) of 5-FU on OMC-1 and OMC-4 cells after 96 hours of incubation with 5-FU was 0.13 micrograms/ml and 9.1 micrograms/ml, respectively. The morphological changes were more prominent in OMC-1 cells than in OMC-4 cells after 192 hours of incubation with 0.1 micrograms/ml of 5-FU. The incorporation of 3H-deoxyuridine into the DNA was inhibited more significantly in OMC-1 cells than in OMC-4 cells even at a low concentration of 5-FU. The intracellular FdUMP and thymidylate synthetase (TS) inhibition rate of OMC-1 and OMC-4 after 96 hours of incubation with 0.1 microgram/ml of 5-FU was 4.7 pmol/g and less than 2.6 pmol/g, 58.7% and 60.0%, respectively. These results suggest that 5-FU sensitivity of cervical adenocarcinoma cell line (OMC-4) is lower than that of cervical squamous carcinoma cell line (OMC-1) and it may owe much not to the TS inhibition rate but to the intracellular FdUMP.

Adenocarcinoma↗

[The effect of endoscopical intratumoral injection of OK-432 in gastric carcinoma].

Many BRMs (biological response modifiers) have been used for post-operative immunochemotherapy. And their usefulness were also reported. Nevertheless it is still unknown that which route, how much doses and which timing are the most effective to administer these drugs. We used BRMs intratumorally and preoperatively. To reconfirm the efficacy of intratumoral injection therapy randomized study was performed in gastric carcinoma. Three hundred and ninety-five cases were entered, 199 cases in group A which were treated preoperatively with OK-432 intratumorally and 196 cases in group B which were control, respectively. In the cases which had marked infiltration of lymphoid cells in tumor sites, the two year survival rate of group A was significantly better than that of group B (p less than 0.05). On the study of recurrent forms, the distal lymph node metastasis was markedly decreased in group A. The ratio of metastasis to the distal lymph nodes in group A was 5-10% lesser than that in group B on the each depth of tumor invasion. The ratio of lymph nodes metastasis was almost similar in the each group, but the number of metastatic lymph nodes was significantly reduced in high grade tumor infiltrated cases in group A (p less than 0.005). These results suggest that preoperative endoscopically intratumoral administration of OK-432 suppresses the lymph node metastasis and improves the postoperative survival rate.

Biological Products↗

Expression of cytokine genes in hematological malignancies.

A substantial number of leukemic blast colonies were formed when conditioned medium of human bladder carcinoma cell line 5637 was added as a stimulator. Recombinant colony-stimulating factor (CSF) also stimulated leukemic blast cell proliferation, leading to colony formation. Furthermore, serum CSF levels in some patients with acute myelogenous leukemia (AML), as detected by sensitive enzyme-linked immunosorbent assay (ELISA), were high. These observations prompted us to study further the expressions of hematopoietic growth factor genes. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in the leukemic blast cells from about 30% of patients with AML by Northern blot analysis using strict hybridization conditions with or without in vitro blast cell enrichment. These findings suggest that the expression of cytokine genes including the GM-CSF gene reflects in vivo phenomena, although no clear relationship between expression of the genes and serum CSF level has been established. Gene encoding tumor necrosis factor alpha (TNF-alpha), lymphotoxin (LT) and transforming growth factor beta (TGF-beta) were sometimes expressed in some malignant hematological cell lines and also some fresh leukemic cells.

Biological Factors↗

Granulocyte-macrophage colony formation in vitro using human non-phagocytic bone marrow cells.

A technique employing silica particles was used to remove cells producing endogenous colony-stimulating factor (CSF) to allow measurement of the level of colony-forming units in culture (CFU-C) in human bone marrow cells. In comparison with the glass-adherence technique, this new approach resulted in a more complete degree of removal of CSF-producing cells and formation of more colonies. This method seems to be useful for performing an accurate assay of exogenous CSF.

Bone Marrow Cells↗

Stimulatory effects of bestatin on human B-cell colony formation.

Bestatin, (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine, is a small molecular immunomodifier. Effects of this compound on human immune function were studied, in vitro, using the human B-cell colony formation technique. B-cell colonies were obtained from enriched B-cell populations placed in conditioned methylcellulose medium containing stimulators and irradiated T-cells as feeders. Addition to the culture of Bestatin at concentrations of 0.1 microgram/ml and 1 microgram/ml led to a significant increase (P less than 0.05) in the number of B-cell colonies and this effect was abolished when irradiated T-cells were not added to the culture. Bestatin increased soluble factor production induced by phytohemagglutinin (PHA)-stimulated T-cells. Such findings suggest that T-cells probably mediate this stimulatory effect of Bestatin on B-cell colony formation.

Adjuvants, Immunologic↗

Effect of human G-CSF on clonogenic cells in acute myeloblastic leukemia.

The effects of purified human native granulocyte colony-stimulating factor (G-CSF) on the growth of clonogenic leukemic blast cells from 10 Japanese patients with acute myeloblastic leukemia (AML) were studied, using an in vitro leukemic blast colony assay. The clonogenic leukemic blast cells from six patients with AML were stimulated to form colonies in viscous medium in vitro by the addition of 100 ng/ml G-CSF. The possibility that G-CSF may be a leukemic blast growth factor warrants further attention.

Adult↗

Demonstration of three distinct immunological disorders on erythropoiesis in a patient with pure red cell aplasia and autoimmune haemolytic anaemia associated with thymoma.

A patient with pure red cell aplasia (PRCA) and autoimmune haemolytic anaemia (AIHA), associated with a thymoma which had already been removed, was studied in order to investigate the pathogenesis of PRCA and AIHA. The autoantibody eluted from the surface of the patient's red blood cells (RBC) reacted with the large E antigen of the Rh complex. Immunoglobulin-G (IgG) purified from the patient's serum suppressed CFU-E and BFU-E but not CFU-GM colony formation in the presence of complement. This antibody was not adsorbed with large E antigen. T-lymphocytes in the bone marrow suppressing autologous CFU-E and BFU-E colonies were demonstrated. Thus, three distinct immunological disorders on erythropoiesis were present in this patient with PRCA and AIHA associated with thymoma in a thymectomized state.

Anemia, Hemolytic, Autoimmune↗

Haematopoiesis in the aged as studied by in vitro colony assay.

Changes occurring in human haematopoiesis with advancing age were studied using an in vitro haematopoietic colony assay in 22 elderly subjects with unexplained anaemia, and in 15 elderly and 15 young subjects without anaemia. Both elderly groups were found to have significantly lower numbers of bone marrow early erythroid-committed progenitors (BFU-E) than the young controls. The elderly anaemic group also showed significantly lower numbers of granulocyte/macrophage progenitors (CFU-GM) than the young controls. However, the responses of the erythroid-committed progenitors in the elderly groups to erythropoietin and burst-promoting activity were similar to those observed in the young controls. Therefore, it is probable that anaemia tends to occur easily in elderly individuals as a result of reduction of reserves of haematopoietic progenitors with advancing age.

Adult↗

Clinical efficacy of endoscopic injections of OK-432 in the treatment of gastric cancer.

A total of 48 patients with gastric cancer were randomly assigned to receive either endoscopic injections of OK-432 plus systemic treatment with intravenously administered 5-fluorouracil and intradermally injected OK-432 (group A) or systemic therapy alone (group B). Morphologic improvement occurred in 7 of the 22 patients in group A. In one patient the tumor mass disappeared completely. In group B morphologic improvement occurred in only 2 of the 26 patients. The survival rate throughout the 24-month period was significantly (P less than 0.01) higher in group A than in group B patients. Thus, local administration of OK-432 by endoscopic injection is effective and is recommended for the treatment of patients with advanced gastric cancer.

Administration, Oral↗