Nephrotoxicity of gold: clinical and experimental studies.
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Biomedical subjects
Publications and source records attributed to S Eto.
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The clinical significance of serum ribonuclease (RNase) assay in acute leukemia was studied. Serum RNases were assayed by the method of Akagi et al. with slight modifications in the serum samples obtained from 50 cases of healthy subjects, 55 cases of acute leukemia before therapy, 18 chronic myelocytic leukemia before therapy, 13 chronic myelocytic leukemia under treatment and 20 reactive leukocytosis. The ratio of acid RNase to alkaline RNase activities (Ac/Al ratio) was statistically increased in acute promyelocytic leukemia, acute myeloblastic leukemia [M2], acute myelocytic leukemia and erythroleukemia (leukemic stage) compared with those in healthy subjects (P less than 0.001). All cases of acute promyelocytic leukemia and most of the acute myeloblastic leukemia [M2], acute myelomonocytic leukemia and erythroleukemia cases had an Ac/Al ratio of above 1.0. In remission of acute leukemia, it is noteworthy that acid and alkaline activities showed no substantial difference from those of healthy subjects. While, on relapse of acute leukemia cases, showing Ac/Al ratio above 1.0 in pretreatment state, Ac/Al ratio increased to above 1.0. Thus, the assay of serum RNases and the calculation of Ac/Al ratio might be an additional method for diagnosing acute leukemia and for assessing their remission and recurrence in some type of acute leukemia.
We investigated the effect of a recombinant human erythropoietin preparation (recombinant Epo) on murine megakaryocyte (MK) colony formation in serum-free and serum-containing culture systems, in order to study the relationship between Epo and megakaryopoiesis. Pokeweed mitogen spleen-conditioned medium (PWM-SCM), a standard source of MK colony stimulator, dose-dependently stimulated MK colony formation in the two culture systems. The plating efficiency of serum-free cultures was almost equal to that of cultures containing serum. Recombinant Epo also dose dependently stimulated MK colony formation in serum-containing cultures. However, in serum-free cultures recombinant Epo alone did not stimulate the growth of MK colonies; with the addition of fetal calf serum (FCS) to the serum-free cultures, recombinant Epo induced the growth of MK colonies. Furthermore, recombinant Epo enhanced MK colony formation through the stimulation of PWM-SCM or murine interleukin 3 (IL-3) in serum-free cultures. Our data show that Epo can act as a stimulator of megakaryopoiesis in collaboration with a factor in serum, or with an MK colony stimulator such as IL-3.
A case of thyroid cancer showing both a high 123I-NaI uptake in primary and metastatic foci with euthyroidism was reported. Extrathyroidal uptake of radioactive iodine is emphasized to be suggestive of metastases of thyroid cancer even in an euthyroid state.
5'-Nucleotidase was found in purified rat liver tritosomes. When tritosomes were subfractionated into the membrane and soluble contents fractions, 73% of the total 5'-nucleotidase activity was found in the membrane fraction and 24% in the soluble contents fraction. Immunoblotting using specific polyclonal antibodies against the rat liver plasma membrane 5'-nucleotidase showed that the mobilities on SDS-polyacrylamide gel electrophoresis of both 5'-nucleotidases in the membrane and contents fractions were identical to that of the enzyme in the plasma membranes (Mr = 72,000). 5'-Nucleotidases in the membrane and contents fractions were sensitive to neuraminidase and converted into a form that was 4 kDa smaller after digestion, as observed in the case of plasma membrane enzyme. 5'-Nucleotidases, both from the membrane and contents fractions, were purified using immunoaffinity chromatography, and the isoelectric points, heat stability, and oligomeric structure of the purified enzymes were compared. Isoelectric focusing and the heat stability test indicated the resemblance of the soluble enzyme to the membrane-bound enzyme. However, the membrane-bound enzyme aggregated in the absence of Triton X-100, whereas the soluble enzyme behaved as a dimer. The topography of 5'-nucleotidase in the tritosomal membranes was studied using antibodies against 5'-nucleotidase and neuraminidase treatment. The inhibition of 5'-nucleotidase were not observed in the intact tritosomal fraction until the tritosomes had been disrupted by osmotic shock. These results show that the active sites and the oligosaccharide chains of 5'-nucleotidase are located on the inside surface of the tritosomal membranes.
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Molecular size heterogeneity of immunoreactive prolactin (PRL) in sera of pregnant women and patients with PRL-secreting pituitary tumor as well as pituitary tumor extract was investigated. "Big big PRL" in the vicinity of the void volume was identified by PRL radioimmunoassay. The ratio of "big big PRL" to "little PRL" was almost constant in normal pregnant women, while the proportion varied from case to case in patients with pituitary tumor. The ratio of "big big PRL" to "little PRL" was significantly (P less than 0.01) larger in these patients (43.3 +/- 9.8%, mean +/- SE) than in pregnant women (13.0 +/- 0.77%). Neither radiation therapy nor thyrotropin releasing hormone (TRH) stimulation significantly affected the ratio of "big big PRL" to "little PRL", while it decreased from 20.5% to 9.5% one month after tumor resection. The elution patterns of the normal human pituitary extract and the tumor extract obtained from patients with PRL-secreting pituitary tumor revealed peaks in identical positions, although the ratio of "big big PRL" to "little PRL" in the tumor extract (38.2 +/- 3.6%) was significantly (P less than 0.01) larger than that in normal human pituitary extract (5.8 +/- 2.8%). These results indicate that "big big PRL" is present in sera of pregnant women and patients with PRL-secreting pituitary tumor, normal pituitary extract and tumor extract. It is also suggested that the increased circulating "big big PRL" observed in patients with PRL-secreting tumor may originate in tumor tissue.
We investigated the percentage of circulating HLA-DR antigen positive (Ia antigen positive: Ia+) T cells and the additive proliferation by non-specific mitogens and thyroid-specific antigens by means of a cytotoxicity test in autoimmune thyroid diseases. Furthermore, we studied the stimulative function of circulating Ia+T cells in autologous mixed lymphocyte reactions. %Ia+T cells were significantly increased in patients with autoimmune thyroid diseases compared with those in normal controls. They were additionally increased by the stimulation of TSH-receptor or thyroid-microsome in patients with Graves' disease, and by the stimulation of thyroglobulin and thyroid-microsome in patients with Hashimoto's thyroiditis. As to the cellular immune function, circulating Ia+T cells stimulated Ia-T cells in autologous MLR in patients with autoimmune thyroid diseases. These data suggest that some of the T cells are already activated in vivo, that the activation of T cells may be by thyroid-specific antigens, and that these activated (Ia+) T cells may be able sequentially to induce the activation of inactivated (Ia-) T cells in autoimmune thyroid diseases.
The immunosuppressive activity of sera from adult T cell leukemia (ATL) patients and culture supernatants of ATL cells and ATL cell lines on B cell responses was examined in vitro. ATL sera and culture supernatants of ATL cells suppressed B cell proliferative and differentiative responses induced with B cell mitogens such as Staphylococcus aureus Cowan I and pokeweed mitogen. The suppressive effect was observed not only in the production of B cell growth factors (BCGF) and B cell differentiation factors (BCDF) by T cells, but also in the responsiveness of B cells to BCGF and BCDF. These results suggest that the immunosuppressive factors produced by ATL cells might act to suppress both the cellular immunity and the humoral immunity, and could have an important role in the induction of immunodeficient states in ATL patients.
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The effect of interleukin 1 (IL 1) on the expression of interleukin 2 receptor (IL 2R/Tac antigen) on human natural killer (NK) cells and the NK-like cell line, YT was studied with the use of a fluoresceinated anti-IL 2R monoclonal antibody and a Spectrum III flow cytofluorometer. IL 2R was expressed on approximately 10% of NK cells. The expression of IL 2R on NK cells was increased to approximately 25% by the in vitro culture with monocytes or IL 1 and to a less extent by the culture with IL 2 or interferon-gamma (IFN-gamma). IL 2R was expressed on approximately 50% of YT cells without any stimulations. The expression of IL 2R on YT cells was increased up to almost 100% by the culture with IL 1 or monocytes, but not with IL 2, IFN-alpha, IFN-beta, IFN-gamma, or lectins such as concanavalin A and phytohemagglutinin-P. IL 1 absorbed with YT cells or murine thymocytes lost both IL 1 activity detected by the stimulation of murine thymocyte proliferative response and enhancing activity of IL 2R expression on YT cells, suggesting that IL 1 has both activities. However, the assay system of the expression of IL 2R on YT cells is much more sensitive than the stimulation of murine thymocyte proliferative response. By the kinetic study, the enhancement of IL 2R expression was induced by only a 2-hr incubation of YT cells with IL 1. This enhancement did not proceed at 4 degrees C or by the treatment of YT cells with actinomycin D or cycloheximide, suggesting that this enhancement is energy dependent and requires the synthesis of RNA and protein but not DNA. Thus IL 1 plays an important role for the regulation of the expression of IL 2R on NK cells, and IL 1-dependent IL 2R expression on YT cells may give us a good model for the study of the molecular mechanism of the regulation of IL 2R expression.
The role of macrophages (monocytes) for the induction of interleukin 2 receptors (IL 2R) on human B lymphocytes was studied by a direct immunofluorescence method with the use of a fluoresceinated anti-IL 2R monoclonal antibody and a flow cytofluorometer. Highly purified B lymphocytes alone did not induce IL 2R on their surface by stimulation with Staphylococcus aureus Cowan I, anti-mu antibody, or pokeweed mitogen. However, the addition of monocytes successfully induced IL 2R on B lymphocytes stimulated with these mitogens in a dose-dependent manner. Interleukin 1 (IL 1) produced by monocytes could partially replace the accessory function of monocytes. In accordance with these results, the proliferation of B lymphocytes and the differentiation to immunoglobulin-producing cells in response to IL 2 were also dependent on monocytes or IL 1. These results suggest that the accessory function of macrophages for IL 2-induced B cell activation is primarily on the induction of IL 2R on B lymphocytes.
The echographic characteristics and ultrasonic tissue characterization of malignant lymphoma are reported. The patient was a 72-year-old man with stage IV malignant lymphoma of medium cell type and had lymphomatous involvements in the liver, the spleen, and peripancreatic, para-aortic, hepatic and splenic hilar lymph nodes. The echo-characteristics were hypoechoic in nature in all these involved lesions and the histologic specimen at the border between the lymphoma lesion and the liver was examined as well as the peripancreatic lymph node from the viewpoint of the ultrasonic tissue characterization. It was concluded that the rich cellularity in the homogeneous nature when compared with the surrounding structure, can produce hypoechoic lesion in routine clinical echograms.
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The effects of calcium, calcium antagonists, and calmodulin inhibitors on the growth of adult T-cell leukemia (ATL) cells were studied in vitro. Fresh ATL cells from patients and established ATL cell lines did not grow well in a low-calcium (less than 0.01 mM) medium. However, their growth was enhanced by the addition of calcium to the medium in a dose-dependent manner. The maximum response was induced at 4 mM calcium, which was higher than that of the normal serum calcium level, 2.5 mM. Other leukemia cells, except ATL, grew well in the low-calcium medium, and their growth was not enhanced by the addition of calcium. Calcium antagonists and calmodulin inhibitors inhibited the growth of ATL cells at the concentration of 10(-5)-10(-7) M, while they did not inhibit the growth of other leukemia cells. Furthermore, the expression of interleukin 2 receptors (Tac antigens) on ATL cells was also enhanced by calcium and was inhibited by calcium antagonists and calmodulin inhibitors. In accordance with these results, the increase of the extracellular calcium concentration resulted in the increase of the intracellular calcium concentration in ATL cells, but not in other leukemia cells. These results suggest that calcium and calmodulin play a critical role in regulating the growth of ATL cells.
The mechanism of immunodeficiency in adult T-cell leukemia (ATL) patients was studied in vitro. Peripheral blood lymphocytes from ATL patients and ATL cell lines such as Hut 102, MT 1, and MT 2 were not activated to proliferate by the stimulation with concanavalin A and suppressed normal lymphocyte proliferative responses induced with concanavalin A when cultured together. The sera from ATL patients and the culture supernatants from ATL cells and ATL cell lines also suppressed normal lymphocyte proliferative responses induced with concanavalin A. By Sephacryl S-200 column chromatography, the suppressive factors were fractionated as a single peak with the molecular weights of 50,000 to 70,000. The suppressive factors were unstable to acid treatment but stable to the treatment with base, heat, freezing-thawing, and trypsin. The factors suppressed the production of interleukin 2 by T-cells and the responsiveness of T-cells to interleukin 2, but not the expression of interleukin 2 receptors on T-cells and the production of interleukin 1 by monocytes. These results suggest that the immunosuppressive factors produced by ATL cells have some roles in the induction of immunodeficient states in ATL patients.
Enzymeimmunoassay (EIA) with monoclonal antibody against human estrogen receptor (ER) from MCF-7 breast cancer cells and radioimmunoassay (RIA) with monoclonal antibody against ER D-5 antigen from human myometrium were applied to human breast tumor, and the results were compared to those of steroid binding assay using the dextran coated charcoal (DCC) method. The rates of coincidence of positivity and negativity of ER between the DCC method and EIA or RIA in 30 human breast tumors were 96.7% (29/30) and 86.7% (26/30), respectively. A highly significant positive correlation was observed between ER values obtained by the DCC method and those by EIA (r = 0.87, P less than 0.001). On the other hand, the correlation between ER values obtained by the DCC method and those by RIA was less significant (r = 0.41, P less than 0.05). The discrepancy between these ER values may be due to the difference of the monoclonal antibody used in each new assay. The above results indicate that EIA and RIA with monoclonal antibody for human ER are useful for clinical use, although the reason for the partial discrepancy of the data between the DCC method and RIA remains to be elucidated.