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Biomedical subjects

J Fujimoto

Publications and source records attributed to J Fujimoto.

At least 343 records · Page 19Linked to original sources
PubMed1984

Danazol binding to steroid receptors in human uterine endometrium.

To understand the mechanism of action of danazol, the binding of danazol to multiple classes of intracellular steroid binding proteins was studied in the human uterine endometrium. Danazol bound to endometrial receptors for estrogen, progesterone, and androgen and seemed to bind to endometrial intracellular corticosteroid-binding globulin and sex-hormone-binding globulin. Danazol occupies almost all binding sites of steroids in the steroid target cells in spite of the presence of endogenous steroids. It is speculated that the binding behavior of danazol may be related to its therapeutic effect on endometriosis.

Binding Sites↗
PubMed1984

Estrogen receptors in brain tumors.

We examined the cytosolic estrogen receptor (ER) level in tumor tissue from 77 patients: 36 meningiomas, 20 gliomas (12 glioblastomas, 2 cerebellar astrocytomas, 2 ependymomas, and 4 medulloblastomas), 8 neurinomas, 7 pituitary adenomas (2 prolactin-producing adenomas, 1 growth hormone-producing adenoma, and 4 nonfunctioning adenomas), and 6 metastatic brain tumors (1 from breast cancer, 4 from lung cancers, and 1 from colon cancer). Nuclear ER levels were assayed in 11 meningiomas and 2 glioblastomas. ER was determined by the dextran-coated charcoal method and calculated by Scatchard analysis. Cytosolic ER was detected in 100% of the pituitary adenomas, 50% of the meningiomas, 50% of the metastatic brain tumors, 25% of the neurinomas, and 15% of the gliomas. In gliomas, only medulloblastomas had ER activity. Nuclear ER was found in three premenopausal women with meningioma. The dissociation constant of the ER complex was, in each case, less than 10(-9) M. These observations suggest that some brain tumors may be responsive to estrogen via the cellular ER.

Adenoma↗
PubMed1984

[Effect of preoperative adjuvant therapy of esophageal carcinoma].

Between January 1970 and December 1983, 148 patients of esophageal carcinoma were treated surgically in the 2nd Department of Surgery, Osaka University Medical School. Among these patients, 70 (48.6%) with suspected invasion to neighboring structures were treated with preoperative chemotherapy, radiotherapy or a combination of both. The chemotherapeutic agents used were tegafur (FT-207)-suppository, bleomycin (BLM) or peplomycin (PEP). Radiotherapy (3000-4000 cGy) for selected cases was begun at the same time as the chemotherapy. Three to four weeks after the chemotherapy and radiotherapy were completed, esophagectomy was performed. The effects of the preoperative adjuvant therapies were investigated in these patients, and the following results were obtained: A marked histological effect, according to the Guide Lines in Clinical and Pathologic Studies for Carcinoma of the Esophagus (Japanese Society for Esophageal Diseases, 1976) was found in 47.4% of the radiotherapy plus FT-207 group, 39.1% of the group receiving radiotherapy alone and 28.6% of the group receiving radiotherapy plus PEP or BLM. Radiotherapy plus FT-207 showed excellent effects (77.8% of this group showed marked histological effects) on well differentiated squamous cell carcinoma, as shown histologically by biopsy specimens. Tumors exhibiting sharp edged margins radiographically and endoscopically, showed a very good histological effect after preoperative radiotherapy. Metastatic lymph nodes present in the irradiation field, whose primary lesion showed a marked histological effect, also gave excellent results. Postoperative radiotherapy is also expected to be equally effective on these cases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Implications of subcellular steroid binding sites in endometrial cancer, determined by an immunofluorescent steroid-antibody technique and biochemical assay.

A discrepancy has been found between the progestogen level necessary for treatment of endometrial cancer and the steroid receptor level detected for the response indicator. Therefore the relationships between the steroid binding quantity detected biochemically and the steroid reactivity determined immunofluorescently was evaluated subcellularly in the endometrial cancers. Estradiol-17 beta and progesterone fluorescences were not always related to the classical steroid receptor binding quantities. These two steroids bound to the nuclear components directly, but heterogeneously. In the biochemical method using fractionated dispersed cancer cells, cellular heterogeneity of the steroid receptor mechanism in a given endometrial cancer tissue was proved. Steroid fluorescence was not related to the steroid-receptor complex quantity in the normal endometrial nucleus. This suggests that the binding of steroid antibody to the steroid-receptor bound already to the nucleus seems to be inhibited due to steric hindrance. Therefore the nuclear steroid fluorescence did not always give the nuclear steroid-receptor complex quantity. These results indicate heterogeneity in the estrogen and progestogen receptor mechanism in endometrial cancer, when studied by the biochemical and immunofluorescent techniques, and that these steroids bind to the nucleus directly and may influence the nuclear mechanism. Therefore, in endometrial cancer progestogen does not always have a therapeutic effect through the progestogen receptor and does not affect the therapeutic effect on any of the cells.

Aged↗
PubMed1984

Strategies for production of monoclonal anti-idiotype antibodies against human B cell lymphomas.

Murine monoclonal antibodies (MAB) against the idiotype (Id) of B lymphocyte malignancies are powerful reagents for the study of these diseases, and are potentially useful for treatment. Different strategies for the production of these anti-Id MAB have been compared. Initially, the Id Ig from nonsecreting B cell tumors was "rescued" by human X mouse or human X human hybridization. These somatic cell hybridizations resulted in the secretion of human Ig in 10 and 100% of the fusions, respectively. In a second step, anti-Id MAB were produced by using the "rescued" Id Ig as immunogen. A more streamlined approach is based on a one-step procedure in which the tumor cell suspension is used as immunogen. This method of immunization, coupled with a four-layer ELISA, results in the detection of anti-Id MAB in a frequency of approximately 1% of the total hybrids. By using a pool of 10 different anti-Id MAB, each reactive with the tumor of one patient, we searched for idiotypic relatedness among a panel of 50 additional tumors. No cross-reactions were found, indicating that our current strategy results in the identification of unique idiotypic determinants among human B cell tumors. Idiotypic Ig can be found in the serum of patients with B cell tumors. Among groups of patients, there is a wide spectrum of serum Id levels, ranging from less than 0.01 microgram/ml to greater than 500 micrograms/ml.

Animals↗
PubMed1983

Spontaneous release of the Leu-2 (T8) molecule from human T cells.

Sensitive enzyme-linked immunosorbent assays (ELISA) for the detection of human T cell antigens in soluble form have been developed. The assays use mouse monoclonal antibodies and specific anti-Leu sera prepared in rabbits by immunizing with Leu antigens absorbed to monoclonal antibody affinity columns. With these assays, Leu-1, -2, and -3 antigen signals from extracts of as few as 5 X 10(3) cells could be detected. When culture supernatants from various cell lines were tested, Leu-2 antigen, but not Leu-1 or Leu-3, was found to be present. Leu-2 antigen was present only in supernatants from T cell lines that expressed Leu-2 on their cell surface. Leu-2 antigen accumulated progressively in the supernatant of low density culture and its presence did not depend on cell proliferation or on fetal calf serum in the culture medium. The Leu-2 antigen in the supernatant was found to have only one Leu-2a determinant, whereas Leu-2 antigen from cell extracts had at least two determinants. The Leu-2 molecule was effectively purified from supernatant with an anti-Leu-2a affinity column. The purified Leu-2 antigen from supernatant of HPB-ALL cells was a single polypeptide chain of 27,000 mol wt, whereas Leu-2 antigen present on HPB-ALL cell surface was composed of two or more identical polypeptide chains of 33,000 mol wt linked by disulfide bonds. Normal human sera and sera from leukemia patients were also examined for the presence of the Leu-2 antigen. Normal human sera contained low levels of Leu-2 antigen but sera from Leu-2-positive leukemia patients had high levels. These results indicate that Leu-2 antigen is released from human T cells under physiological conditions.

Animals↗
PubMed1983

Serum hormone and steroid hormone receptor levels during luteal-phase and long-term treatment with danazol.

This study was designed to clarify the effects of danazol on levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, progesterone (P), and 17 beta-estradiol and endometrial steroid receptors (for estrogen [ER], progestin [PR], and androgen [AR] ) during luteal-phase and long-term treatment. These levels were compared with midluteal-phase levels for a histologically in-phase endometrium. Danazol given during the luteal phase to patients with in-phase endometrium decreased endometrial steroid receptor levels (total ER and total PR), and decreased serum P, LH, and FSH levels. Ten of the 17 patients treated (59%) still had in-phase endometrium. Danazol (400 mg/day) given for 1 month or more to patients with pelvic endometriosis increased serum LH and FSH levels within the normal range and endometrial total ER and PR levels. It appears that the effects of short-term and long-term treatment with danazol on serum hormone and endometrial steroid receptor levels differ.

Adult↗
PubMed1983

Four distinct antigen systems on human thymus and T cells defined by monoclonal antibodies: immunohistological and immunochemical studies.

Human thymus and T cell antigens were identified by using four distinct monoclonal antibodies (MoAb), designated 2D5, 5B3, 7A5 and 9D4. 2D5 antibody reacted with most human thymocytes and a few peripheral lymphocytes as well as with a subpopulation (20%) of bone marrow cells, and precipitated a 45K molecular weight (mol. wt.) component from 125I-labelled thymus cell lysate. 7A5 antibody also reacted with the majority (80%) of thymocytes but neither with peripheral lymphocytes nor with bone marrow cells. The antigen detected by 7A5 was a glycoprotein consisting of 48K and 12K mol. wt. components, which were non-covalently associated with each other. 5B3 reacted with virtually all of human thymus and T cells but not with the majority of B cells and bone marrow cells. This reagent precipitated a 72K mol. wt. glycoprotein from thymus and T cells. An additional 65K mol. wt. glycoprotein was precipitated by 5B3 together with the 72K mol. wt. component, but with poor reproducibility. 9D4 antibody, on the other hand, reacted with a 200K mol. wt. component from thymus and T cells as well as 220K and 210K components from the non-T cell fraction of tonsil lymphocytes. Whereas antigens detected by 2D5 and 7A5 appeared to be highly expressed on cortical thymocytes, the antigen defined by 5B3 occurred much more abundantly on medullary thymocytes and peripheral T cells than on cortical thymocytes. Based on the data described above, it is suggested that 7A5, 5B3 and 9D4 MoAb recognize human homologues of mouse TL, Ly-1 and Ly-5 antigens, respectively, whereas 2D5 antibody seems to resemble OKT10, as described by others.

Antibodies, Monoclonal↗
PubMed1982

Surface antigenic phenotypes of human T-cell leukemia corresponding to those of post-thymic T cells.

Leukemic cells from eight adult patients with various types of T-cell leukemias, including one patient with lymphosarcoma cell leukemia (T-LSL), two patients with chronic lymphocytic leukemia (T-CLL), and five patients with adult T-cell leukemia (ATL), were analyzed for their surface antigenic phenotypes with a series of monoclonal antibodies directing to human T-cell differentiation antigens. All of the leukemic T cells studied were regarded as being of post-thymic T-cell origin because of their ability to form rosettes with sheep red cells under the condition at 4 degrees C but not 37 degrees C as well as the expression of human Ly-1-like but not TL-like antigen on their cell surfaces. By using monoclonal antibodies to a variety of human of three distinct categories. Thus, one patient with T-LSL had cells with Leu-1+2a+3a+ phenotype, which might reflect possible post-thymic precursor T cells, whereas one patient with T-CLL had cells with the same phenotype (Leu-1+2a+3a-) as normal cytotoxic/suppressor T cells. The latter cells also expressed Ia antigens as defined by monoclonal antihuman Ia antibody. The remaining six cases, including one T-CLL and five ATL patients had leukemic cells with the same phenotype (Leu-1+2a-3a+) as normally found on helper/inducer T cells, despite distinct clinical and immunological features between T-CLL and ATL. Some clinical findings observed in those patients may reflect functional activities retained by their leukemic T cells.

Antibodies, Monoclonal↗
PubMed1981

Human thymus antigen: characterization and its expression on human leukemias.

Specific anti-human thymus xenoantiserum (ATS) was utilized for characterizing a human thymus antigen (HTA) preferentially expressed on human thymocytes. Binding of ATS with different cell types was studied by immunofluorescence and immunoperoxidase techniques, as well as by radioimmunoprecipitation (RIP) followed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). ATS reacted selectively with the majority (87%) of human thymocytes among normal lymphoid cell populations tested. In the thymus, HTA was expressed largely on cortical thymocytes but not on those cells located in the thymic medulla. When 20 cases of different types of lymphatic leukemias were studied with ATS, HTA was found on acute lymphoblastic leukemia cells rosetting with sheep erythrocytes (T-ALL) but not on other lymphatic leukemia cases, including chronic lymphocytic leukemia cells rosetting with sheep red blood cells (T-CLL). SDS-PAGE analysis of immunoprecipitates formed between ATS and radiolabeled cell-surface components of human thymocytes demonstrated that ATS bound a 48,000-molecular-weight component that could be adsorbed to Sepharose 4B coupled with Les culinaris hemagglutinin and could be labeled by periodate-tritiated borohydride, indicating that HTA is a sialoglycoprotein. Similar antigen molecules were also precipitated by ATS from T-ALL cells but not from other lymphatic leukemia cells. Five T-ALL-derived cell lines were tested with ATS by immunofluorescence and by RIP and SDS-PAGE, but only two cell lines (MOLT-3 and P12/Ich) possessed HTA molecules on their cell membrane.

Animals↗
PubMed1981

Analysis of human T-cell antigens by one- and two-dimensional polyacrylamide gel electrophoresis.

One- and two-dimensional polyacrylamide gel electrophoresis (PAGE) was performed on immunoprecipitates formed between anti-human T-cell xeno-antiserum (ATS) and cell-surface glycoproteins of human lymphocytes, that had been radioiodinated by lactoperoxidase and purified on a Lentil lectin-coupled Sepharose 4B column. In some experiments, the cells were 3H-labeled by periodate-tritiated borohydride. ATS that was absorbed with B cells recognized a number of cell-surface antigens expressed preferentially on human thymus and T cells, with molecular weights of 150K (T150), 94K (T94), 72K (T72), and 65K (T65) daltons. Whereas T150 appeared to consist of multiple components of heavily sialylated glycoproteins and to be expressed largely on thymus and T cells, and to a much lesser extent on B cells, the remaining T94, T72, and T65 glycoproteins seemed to be present on thymus and T cells but absent from B cells. Two-dimensional PAGE analysis of these T-cell glycoproteins precipitated by ATS demonstrated that T94 was an acidic glycoprotein with pI of 4, while T72 and T65, the latter being found on thymus and T cells but not on T cell-type leukemic cells, exhibited marked electric charge heterogeneity with pI ranging from 4 to 7. These data clearly suggest that human thymus and T cells possess a complex antigenic make-up on their cell surfaces, comparable to that of mouse T cells with a variety of Ly antigen systems.

Antigens, Surface↗