Characterization of the erythropoietin receptor on a Friend murine erythroleukemic cell clone, TSA8.
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Biomedical subjects
Publications and source records attributed to T Kitamura.
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Seventy-four new cases of prostatic carcinoma treated between 1981 and 1985 were analyzed. The patients were between 40 and 86 years old with a mean age of 72.2 +/- 7.7 years. More than 70% of the patients had clinical stage C and D carcinoma. All cases proved histologically to be adenocarcinoma of the prostate. Eighteen patients had well differentiated, 21 moderately differentiated and 35 poorly differentiated adenocarcinoma. Various hormonal treatments were performed as the initial treatment in 88.9% (64/72) of the cases. Among them, 37 cases were treated by estrogen and 22 cases by luteinizing hormone releasing hormone analogues. Fourteen of 64 patients (21.9%) who received hormonal treatment discontinued the therapy within 10.1 +/- 9.1 months because of relapse of the disease or no therapeutic response. Salvage therapy following hormonal treatment were chemotherapy (9/14) and radiation therapy (4/14). During the 5-year follow up 12.1% (9/74) of the patients died due to prostatic carcinoma.
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This paper presents interesting morphological findings, which have never been previously reported, on tumor tissues after a local injection of an anticancer agent into three patients with malignant glioma. Following a craniotomy, 0.5 mg of Adriamycin (ADM) was injected through an Ommaya reservoir into the tumor bed. Light microscopy of the recurrent tumor and surrounding necrotic tissue revealed massive coagulation necrosis of the tumor tissues and fibrinoid necrosis of vascular channels, centering at the tip of the Ommaya tube. In the surrounding area of the massive coagulation necrosis, considerable reactive collagenous tissue, infiltrating lymphocytes and foreign body giant cell were found as well as so-called "organized" necrotic tissue. Electron microscopic findings of the same specimens revealed deposits of lipofuscin, lipid droplets, lysosome, abundant myelin figures and fibrous strands. It can therefore be assumed that this or similar anticancer agents, when may be directly incorporated into the residual tumor cells, are apparently reduced by coagulation necrosis and reactive collagenous tissue.
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From 1975 to 1986, 15 cases (2%) of metastatic calcification associated with an underlying malignancy were found in a review of 702 autopsied cases with histories of malignancy. These underlying malignancies included 7 cases of lung cancer, 6 cases of malignant lymphoma, one case of breast cancer, and one of urinary bladder cancer. Squamous cell carcinoma was of the histological type most often associated with metastatic calcification in lung cancer, and ATL in malignant lymphoma. Hypercalcemia was found in 10 (83%) out of cases, and almost all were accompanied by renal dysfunction. Calcium deposits were most frequently observed in the kidneys and the lungs. It has been suggested that metastatic calcification in the lungs and kidneys of a patient with a history of malignancy showing hypercalcemia is sometimes accompanied by respiratory and renal dysfunction, causing the patient's condition to deteriorate.
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The mechanism of phagocytosis by Kupffer cells is still unknown. In this study we found that trifluoperazine, chlorpromazine, and W-7, drugs which bind to Ca2+-calmodulin and inhibit its interaction with other proteins, inhibit phagocytosis by cultured Kupffer cells using polystyrene beads, time-lapse VTR systems, and fluorescent staining techniques. Inhibitory effects of these drugs on phagocytosis suggests that the Ca2+-calmodulin system may be involved in this complex cellular function and the integrity of the cytoskeletal system of Kupffer cells is essential to this phenomenon.
The lateral reticular nucleus of the medulla oblongata (LRN) in the rat was observed after injecting horseradish peroxidase (HRP) bilaterally into the anterior lobe of the cerebellum; the inferior cerebellar peduncle had been cut unilaterally prior to the HRP injections. HRP-labeled neurons were seen bilaterally in the LRN; 89% in the contralateral, and 11% in the side ipsilateral to the pedunculotomy. The labeled neurons in the LRN ipsilateral to the pedunculotomy were assumed to send their axons to the anterior lobe of the cerebellum via the controlateral inferior cerebellar peduncle. Of these neurons, 60, 11 and 29% were distributed in the magnocellular, subtrigeminal and parvicellular divisions of the LRN, respectively.
The distribution of messenger RNA for glial fibrillary acidic protein (GFA-protein) of cow and rat brains was studied by an in situ hybridization technique using a tritium-labeled cDNA probe and autoradiography. The results were compared to the findings of GFA-protein immunohistochemistry. The signals of GFA-protein mRNA were detected on the perikaryal cytoplasm of astroglia observed in the following areas: the subpial area and the white matter of the cerebrum and cerebellum of the cow and the rat; gray matter of cow spinal cord; the thalamus, pontine reticular formation and white matter of the rat brainstem. All of these areas contain astroglia which are strongly positive for GFA-protein immunohistochemistry. On the other hand, we could detect no GFA-protein mRNA-positive glial cells in the areas where astroglia are negative for this immunostaining. These results indicate that the regional differences in the amount of GFA-protein in astroglia depend primarily on the degree of expression of their GFA-protein gene.
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Various modes of high-performance liquid chromatography, gel filtration, ion-exchange chromatography, hydrophobic interaction chromatography, reversed-phase chromatography and metal chelate affinity chromatography, were investigated for the separation of membrane proteins. All were found applicable to membrane proteins, although the usefulness of each mode differed. For satisfactory results it was important to select appropriate elution conditions. The type and concentration of detergent was of special importance. The effects of other conditions, flow-rate, gradient steepness, type of buffer and salt, eluent pH, etc., were similar to those observed for soluble proteins.
The antitumor effect of combined use of cis-diamminedichloroplatinum(II) (CDDP) and verapamil, a calcium influx blocker, was examined in neuroblastoma transplanted to BALB/c athymic mice. The response of the tumor to CDDP was related to the dose administered. Regression of the tumor was observed when CDDP was administered at 4.2 mg/kg/injection. The retardation of tumor growth was observed in the group to which CDDP was administered at 2.1 mg/kg/injection. When verapamil was administered with CDDP, regression of the tumor was observed in the group treated with CDDP at 2.1 mg/kg/injection, and the retardation of tumor growth was observed in the group treated with CDDP at 1.4 mg/kg/injection. These results indicate that verapamil enhances the antitumor effect of CDDP against transplanted neuroblastoma in BALB/c athymic mice.
We have studied the internalization of 125I-erythropoietin (Epo) and regulation of Epo receptors by the ligand in a murine erythroleukemia cell clone, TSA8. To determine internalization, a high-salt acid wash was performed. Internalization of 125I-Epo was found in TSA8 cells as well as in fetal mouse liver cells (FMLC), although the percentage of internalized radioactivity reached 40% after incubation at 37 degrees C for 150 min and was lower than that in FMLC. Exposure of TSA8 cells to unlabeled Epo resulted in a rapid, time-dependent reduction in 125I-Epo binding activity. The net loss of the activity was related to the ambient Epo concentration and 5 X 10(-8)M Epo induced approximately 80% loss of total binding capacity. Scatchard analysis of the binding data revealed that the high-affinity receptor number was decreased but the affinity was increased in the Epo-treated cells. In low-affinity receptors, however, the receptor affinity was decreased and the receptor number was not changed much by preincubation with Epo. These results suggest that the decrease in 125I-Epo binding activity after preincubation with unlabeled Epo is mainly accounted for by a decrease in the number of high-affinity receptors, and the high-affinity receptors play an important role in the biological response to Epo.