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Biomedical subjects

T Okabe

Publications and source records attributed to T Okabe.

At least 415 records · Page 23Linked to original sources

Elimination of small cell lung cancer cells in vitro from human bone marrow by a monoclonal antibody.

We report here a useful method for elimination of small cell lung cancer cells in vitro from bone marrow. A monoclonal antibody, TFS-2, which mediates complement lysis and recognizes an antigen present on small cell lung cancer cells but not lymphoid cells or bone marrow cells, was used to clear infiltrated bone marrow. The antibody in the presence of complement effectively killed tumor cells, but it was not cytotoxic to bone marrow cells. When mixed populations consisting of tumor cells and bone marrow cells were treated with antibody and complement, the tumor cells were also effectively killed, except when large numbers of bone marrow cells were present, whereas TFS-2 had no significant effect on bone marrow stem cells, as judged by colony-forming unit assays.

Animals↗

Familial elevation of serum angiotensin converting enzyme.

We report here a familial clustering of elevated serum angiotensin converting enzyme (ACE) levels. The patient is a 58-year-old Japanese female who had been in excellent health until age 45 when she developed an occlusion of the left central retinal vein. She was otherwise in excellent health, and no laboratory abnormality except a marked elevation of serum ACE level (625 nmol/min/ml; normal range; 22-40 nmol/min/ml of serum) was found. Her blood pressure was within normal limits (140/80 mmHg). There was no evidence for the diagnosis of sarcoidosis, Gaucher's disease, leprosy, hyperthyroidism, diabetic retinopathy, or liver disease. One of her two sisters also showed a marked increase in serum ACE activity (303 nmol/min/ml), and remarkably high levels of serum ACE (276 and 294 nmol/min/ml) were demonstrated in both sons of this sister. All the members of this family have been in excellent health. The serum ACE activity was activated by chloride and cobalt ions, and inhibited by EDTA, captopril and rabbit antiserum to purified human plasma ACE. Thus our study showed a familial clustering of elevated serum ACE in individuals who did not have conventional disease patterns associated with elevated serum ACE.

Angiotensin-Converting Enzyme Inhibitors↗

Prognostic evaluation of tracheobronchial reconstruction for bronchogenic carcinoma.

Fifty-two patients have undergone tracheobronchial reconstruction for bronchogenic carcinomas over a 20 year period and have been evaluated from the view point of prognosis. Five-year survival rates of the patients undergoing reconstructive operations were as follows: 35% for the total group, 50% for those with squamous cell carcinoma, and 64% for those with Stage I and II disease. No patients with adenocarcinoma or Stage III disease have survived more than 5 years. However, the number of patients with early adenocarcinoma was too small for us to conclude that the histologic type per se affected survival. Six of eight patients with sleeve lobectomy and pulmonary artery reconstruction died within 2 years, 7 months postoperatively. Five of seven patients died within 1 year after carinal reconstruction. However, two are alive at 4 months and 2 years, 9 months after left or right sleeve pneumonectomy. In summary, any types of lobectomy or pneumonectomy with reconstruction of the tracheobronchial tree can be conducted in patients with Stage I and II lung cancer. Sleeve lobectomy with pulmonary artery reconstruction can be an alternative to pneumonectomy when pneumonectomy is contraindicated because of low cardiopulmonary reserve. In patients undergoing reconstruction of the carina, prophylactic radiation therapy may be necessary during the postoperative course.

Adenocarcinoma↗

Transforming genes in human leukemia cells.

High-molecular weight DNAs of fresh bone marrow cells from 32 patients with fresh leukemia were assayed for the presence of transmissible activated transforming genes by a DNA-mediated gene transfer technique using NIH/3T3 cells. DNAs of bone marrow cells from four of the 32 patients induced transformation of NIH/3T3 cells. Two of the four cases, a chronic myelogenous leukemia and an acute lymphocytic leukemia, contained activated N-ras oncogenes. Molecular cloning and nucleotide sequence analysis revealed that the lesion responsible for the transforming activity was localized to a single nucleotide transition from guanine to thymine in codon 12 of the predicted protein in each of the two cases. These observations indicate that activation of N-ras oncogenes is independent of the specific stage of cell differentiation or the leukemia phenotype. The other two transforming genes associated with an acute myelogenous leukemia and an acute lymphocytic leukemia showed homology neither with members of the ras gene family nor with the human Blym-1 gene. Thus, the NIH/3T3 transfection assay frequently detects activated N-ras oncogenes in human leukemias, while other transforming genes, distinct from the ras gene family, can be detected in some leukemias by the transfection assay.

Autoradiography↗

Recombinant immune interferon inhibits leukemic cell growth by a monocyte-macrophage-mediated mechanism.

We have investigated direct and monocyte-macrophage (Mono/M phi)-mediated indirect effects of recombinant immune interferon (IFN-gamma) on the growth of established leukemic cell lines (K562, KG1, ML1, HL60, U937, and THP1). The direct antiproliferative effects of IFN-gamma on these leukemic cells were mild or negligible, when estimated by 3H-thymidine incorporation. Indirect effects were assessed by the growth pattern of leukemic cells cocultured with Mono/M phi that were pretreated with INF-gamma. While the leukemic cell growth was slightly suppressed by untreated Mono/M phi, this suppression was significantly augmented by the treatment of Mono/M phi with IFN-gamma (10-10,000 U/ml). In addition, the indirect effects of IFN-gamma on leukemic cell growth were examined at different stages of maturation of Mono/M phi. The augmentation of cytotoxicity was detected only when mature Mono/M phi were treated with INF-gamma. This suggests that IFN-gamma acts on tissue macrophages and augments their cytotoxicity against leukemic cells.

Cell Division↗

T-cell receptor gene rearrangement in a patient with common acute lymphocytic leukemia.

Using a beta-chain cDNA probe of the T-cell receptor, we detected T-cell receptor gene rearrangement in leukemic cells from an adult patient with common acute lymphocytic leukemia (cALL). The leukemic cells expressed non-T, non-B cell marker profiles (CALLA+, J5+, Leu-1-, Leu-4-, Ia+, B1-, c-Ig mu- and TdT+). This is the first reported case of cALL with T-cell receptor gene rearrangement and/or deletion.

Adult↗

Pulmonary macrophage: a major source of lipoprotein lipase in the lung.

The lipase released by heparin infusion into perfused rat lungs is shown to be identical with lipoprotein lipase on the basis of the following characteristics: 1) it required plasma for full activity; 2) it was largely inhibited by 1 M NaCl; and 3) it bound to a heparin-Sepharose gel and eluted with buffer containing 1.5 M NaCl. Macrophages prepared from rat lungs released a considerable amount of lipoprotein lipase, with characteristics similar to those of the lipoprotein lipase released from heparin-perfused rat lungs. Pulmonary surfactant-producing type II pneumocytes did not cause a significant release of lipoprotein lipase. No apparent lipoprotein lipase activities were detected in the conditioned medium of other lung cells from which macrophages had been selectively removed.

Animals↗

Large cell carcinoma of the lung associated with marked eosinophilia. A case report.

A case of large cell carcinoma of the lung which produced eosinophil colony stimulating factor and eosinophil chemotactic factor was reported. A 52-year-old Japanese man with a tumor in the left upper lobe of the lung underwent left pneumonectomy. Marked eosinophilia persisted especially after recurrence, with a maximum peripheral leukocyte count of 161,000/mm3, of which 78% consisted of eosinophils. The patient died of pulmonary insufficiency 18 months after surgery. At autopsy, metastatic tumor tissues and almost all organs were markedly infiltrated with eosinophils, especially the spleen, and there was marked proliferation of eosinophils in the bone marrow. Eosinophil colony stimulating factor production by the transplanted tumor in a nude mouse was confirmed by use of a human bone marrow culture assay system. Eosinophil chemotactic factor production by metastatic tumor tissue also was proved by a modified micro-filter technique.

Biological Assay↗

Sarcoid granulomas metabolize 25-hydroxyvitamin D3 in vitro.

Sarcoid granulomas metabolized 25-hydroxyvitamin D3 to two unidentified metabolites during in vitro incubation. A two-step high pressure liquid chromatography system revealed two unique elution positions of these sarcoid-derived metabolites that exactly comigrated with the elution positions of 5(Z)-19-nor-10-oxo-25(OH)D3 and 5(E)-19-nor-10-oxo-25(OH)D3, respectively. These unique metabolites did not bind specifically to a protein receptor for 1,25(OH)2D3.

Biopsy↗

Establishment of a human colony-stimulating-factor-producing cell line from an undifferentiated large cell carcinoma of the lung.

Two different types of lung cancer, a squamous cell carcinoma designated as OTUK, and an undifferentiated large cell carcinoma named as T3M-10, were investigated in vitro; both produced a moderate neutrophilia in each patient. In order to analyze this phenomenon, primary cultures were performed. Epithelial cells attached and grew in both of the cultures. The conditioned medium from both tumor cells revealed high colony-stimulating-factor (CSF) activities. From T3M-10 tumor cultures, a new CSF-producing cell line has been established. T3M-10 cells have been continuously propagated during the last 28 months and produced CSF. Chromosomal analysis revealed the cell line to be a human aneuploid one with a near-diploid mode. These results indicate that the two different types of lung cancers produce CSF, which may have stimulated granulopoiesis in vivo in the patients as well.

Adult↗

Isolation and characterization of vitamin-A-storing lung cells.

Vitamin A-storing cells have been shown to be distributed among various organs and tissues, including the lungs. In order to investigate this unique type of cell, the in vitro isolation has been carried out from rat lungs. Lungs were perfused with EGTA and collagenase solution in situ, and were digested with trypsin-collagenase solution at 60-min intervals for 2 h. Then, the cell suspensions obtained were incubated at 37 degrees C in F-10 medium supplemented with 10% fetal bovine serum (FBS) for 72 h. Non-adherent cells were then removed by vigorous washing with medium, and the resultant cell monolayer was harvested with trypsin to remove the contaminating macrophages. These cell fractions were shown to contain more than 96% of vitamin A-storing cells, judged by electron and fluorescence microscopic examinations. The cells grown in vitro retained well the overall morphology characteristic of the vitamin A-storing cells found in lung tissues. The isolated cells grew well in vitro and the growth was inhibited by D-valine or cis-hydroxyproline. The progeny of the cells still contained vitamin A lipid droplets after several transfer generations. Characteristic networks of fibronectin were also demonstrated around the cells. These results have shown that vitamin A-storing cells in the lung was successfully isolated from rat lungs and the cells possessed fibroblast-like characters storing vitamin A in small lipid droplets.

Animals↗

Long-term cultivation and differentiation of human erythroleukemia cells in a protein-free chemically defined medium.

To examine whether a human erythroleukemia cell line, K-562, can proliferate and differentiate without protein supplements, long-term cultivation of the cells was carried out in a protein-free chemically defined medium. By the use of stepwise decreases in the fetal bovine serum concentration, continuous growth of K-562 cells was established in a protein-free F-10 medium. The cells have been propagated in this medium for 3 years. The population-doubling time of the cells is about 30 hr. Growth was not stimulated by the addition of insulin, epidermal growth factor, fibroblast growth factor, multiplication-stimulating activity, transferrin, platelet-derived growth factor, or dexamethasone. Addition of serum stimulated the cell growth slightly and increased the saturation density. The saturation density of the cells could be increased to that seen with serum-supplemented cultures by changing the serum-free medium daily. The cells synthesized significant amounts of hemoglobin in the presence of hemin without serum supplementation. The results suggest that the human erythroleukemia cells grown in a protein-free medium do not require serum components for their growth or hemin-induced hemoglobin synthesis and provide an excellent model for better understanding of the growth and differentiation of human leukemia cells.

Butyrates↗

A ten-year experience with surgical resection for patients with metastatic lung tumors.

Removal of metastatic lung tumor was performed for 27 patients in a period from January, 1972 to December, 1981. They included 22 carcinomas and 5 sarcomas. Diagnosis as having lung metastasis was made after removal of the primary tumor in 18 patients and at the time of the first detection of the primary tumor in 4 patients. In 5 patients the operation for the metastatic tumor preceded that for the primary malignancy. Metastatic tumors were localized in one lobe in 13 patients. Thirteen of the 27 patients underwent lobectomy and 14 received other types of operation, with or without hilar and/or mediastinal lymphnode dissection. Four patients underwent bilateral thoracotomy. Survival rates at 3 and 5 postoperative years of the group of patients who underwent the operation for primary malignancy first were both 49 percent. The number of lesions removed or the type of operation did not seem to have correlations with the survival rate. Patients whose tumor-free interval was more than 40 months tended to survive longer than those who had an interval less than 40 months. The group with a tumor doubling time of more than 50 days showed a higher survival rate than the group with a doubling time of less than 50 days. Of the 4 patients thoracotomized bilaterally 2 are alive for 20 and 34 months postoperatively, while the other 2 died at 20 and 65 months after the operation. In the selected patients with metastatic lung tumors, surgical treatment can be conducted with a reasonably good result, even though the metastatic malignancy is multiple or bilateral.

Carcinoma↗

Rejection monitoring by lymphocyte blastogenesis assay in canine lung allotransplantation.

Seventy-seven adult mongrel dogs underwent left lung transplantation to study the immunological detection of posttransplant rejection response using the lymphocyte blastogenesis assay. Experimental animals were divied into 3 groups; control autotransplantation (4 dogs), control allotransplantation (32 dogs) and immunosuppressed allotransplantation (41 dogs). The lymphocyte blastogenesis assay included mixed lymphocyte reaction (MLR), lymphocyte reactivity to lectins (PHA, ConA and PWM) and spontaneous blastogenesis in peripheral lymphocyte culture methods. The latter two tests were performed in serial blood samples up to the 38th posttransplant day. In the control autotransplant group there were no particular changes in posttransplant PHA reactivities. In the animals with lung allograft, results of preoperative MLR between donor and recipient showed no particular relationships to posttransplant rejection response. The recipient, however, showed a decreased response to PHA and an increased spontaneous blastogenesis at the period undergoing rejection which were confirmed by blood samples taken within 2 days before sacrifice of animals whose transplant specimens showed apparent histologic findings of rejection. In the immunosuppressed allotransplantation group, those findings of PHA response and spontaneous blastogenesis had often preceded the rejection episode detected on chest x-ray films, whereas there were no particular changes in both parameters of dogs bearing enhanced allografts. The serial detection of spontaneous blastogenesis and PHA reactivity in peripheral lymphocyte may be one of the useful methods for early prediction of rejection episode in lung transplantation.

Animals↗