[Clinical significance of GSA-2 binding glycoprotein assay as a tumor marker].
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Blotting, Western↗
Biomedical subjects
A Okano
Publications and source records attributed to A Okano.
[Calcium metabolism in tuberculosis].
To investigate the role of Ca metabolism in granulomatous lung diseases, 187 patients with pulmonary tuberculosis 42 patients with sarcoidosis, and 47 patients with pneumonia were examined. The mean value of serum Ca on admission in tuberculosis patients was significantly lower than in patients with sarcoidosis. Of 183 patients with tuberculosis, 69 patients (38%) showed Ca level lower than normal range. The longitudinal observation of serum Ca level in 33 drug-responsive patients with tuberculosis disclosed that mean Ca level rose significantly at the third month of treatment, and maintained the similar level up to the sixth month. These findings suggest that the dynamics of Ca metabolism seen in tuberculosis were similar to that in pneumonia and differed from that in sarcoidosis, although both tuberculosis and sarcoidosis are characterized histologically by granuloma formation induced by cell-mediated immunity. To explain changes in Ca level, the chronological analysis of serum Vitamin D level was done, and it showed no correlation with serum Ca level. The lower serum Ca level on admission and their normalization according to the improvement of clinical course in tuberculosis have not been reported yet. It seems that there are responsible factors other than Vit D for Ca level fluctuation, and further studies are needed.
Adult↗
Synergistic regulatory effects of interleukin 6 and interleukin 1 on the growth and differentiation of human and mouse myeloid leukemic cell lines.
We analyzed the effect of recombinant human interleukin 6 (IL-6), in combination with human recombinant interleukin 1 alpha (IL-1 alpha), on the growth and differentiation of several human and mouse myeloid leukemic cell lines, specifically U937, HL-60, M1, and its subclone M1-3b-N, into macrophage-like cells. IL-6 and IL-1 inhibited the growth of U937, M1, and M1-3b-N in a dose-dependent manner. Treatment of these cells with both IL-6 and IL-1 resulted in either an additive or a synergistic growth inhibition. IL-6 alone induced moderate differentiation of U937 and M1-3b-N, but the combination of IL-6 and IL-1 synergistically augmented this differentiation. In M1, only the combination of IL-1 and IL-6 resulted in differentiation. These two cytokines, whether alone or in combination, did not influence the growth and differentiation of HL-60. Therefore IL-6 in conjunction with IL-1 can induce differentiation in several human and mouse myeloid leukemic cell lines, although this effect varies with cell type. IL-6 did not stimulate the expression of IL-1 mRNA or IL-1 activity in U937 cells. IL-1 also failed to stimulate IL-6 production. Furthermore, the differentiation of U937 cells induced by IL-6 was not neutralized by antibody against either IL-1 alpha or IL-1 beta. The minimal differentiative effect of IL-1 was not affected by anti-IL-6 antibody. Therefore IL-6 and IL-1 appear to provide distinct signals for differentiation.
Animals↗
Continuous perfusion with interleukin 6 (IL-6) enhances production of hematopoietic stem cells (CFU-S).
The in vivo effect of human recombinant IL-6 on hematopoietic stem cells (colony forming units in spleen, CFU-S) was investigated. Normal mice perfused with IL-6 for 7 days showed an increase in the serum level of IL-6 in a dose-dependent manner. This increase was accompanied by a dramatic enhancement (approximately 8-fold) in the number of spleen CFU-S 7 days after starting perfusion, although heat-treated IL-6 did not exhibit any activities. Enhanced CFU-S number returned to normal at 13 days after cessation of perfusion. These results suggest that IL-6 could be valuable for treating various forms of hematopoietic depletion.
Animals↗
Autoantibodies to each protein fraction extracted from cerebral endothelial cell membrane in the sera of patients with multiple sclerosis.
Damage to the blood-brain barrier (BBB) occurs in multiple sclerosis (MS), probably due to an immunological mechanism. Anti-endothelial cell antibodies may play a pathogenetic role in the BBB damage. Our previous studies led us to search for which protein fraction extracted from cerebral endothelial cell membrane was reactive to antibodies in the sera of patients with MS. The antibodies to each protein fraction extracted from the rat cerebral endothelial cell membrane were studied in patients with MS, other neurological diseases and controls using an enzyme-linked immunosorbent assay (ELISA) method. The patients with active relapsing MS (P less than 0.01) displayed significantly higher levels of immunoglobulin G (IgG) binding to the endothelial cell membrane fraction than did the controls. The sera of the same patients (P less than 0.001) also showed significantly higher levels of antibodies to fraction I (8.0 kDa) than did the normal controls. The high levels of IgG binding to fraction II (11.0 kDa) and III (12.3 kDa) were significantly increased in the sera of patients with active relapsing MS compared to normal controls (P less than 0.01). The immune response to the protein fraction extracted from the cerebral endothelial cell membrane fraction may indicate a result of the BBB damage in the case of MS.
Adolescent↗
Effects of interleukin-6 on hematopoiesis in bone marrow-transplanted mice.
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Animals↗
In vitro expansion of the murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6. Application to bone marrow transplantation.
The synergistic action of interleukin 6 with interleukin 3 on the proliferation of a murine hemopoietic stem cell population in a short-term liquid culture system was examined by radioprotective assay. The numbers of colony-forming units in spleen (CFU-S), together with granulocyte/macrophage colony-forming units and viable nucleated cells, were found to increase markedly in culture in the presence of both IL-3 and IL-6, compared with the presence of IL-3 or IL-6 alone. The peak CFU-S value in response to the combination of IL-3 and IL-6 was obtained 6 days after culture initiation, exceeding 5-fold of the input value. Consistent with these data, marrow cells cultured with both IL-3 and IL-6 for 6 days were shown to have a much higher capability of rescuing lethally irradiated mice than did controls. The results may portend the potential clinical use of the combination of IL-3 and IL-6, in particular, in bone marrow transplantation.
Animals↗
Implantation of fibroblasts transfected with human granulocyte colony-stimulating factor cDNA into mice as a model of cytokine-supplement gene therapy.
A fibroblast-mediated gene delivery method was used for the endogenous expression of human granulocyte colony-stimulating factor (G-CSF) as a model for cytokine supplement therapy. Human G-CSF cDNA was inserted into the plasmid expression vector BMGNeo, which contains a partial sequence of bovine papilloma virus and a selectable marker gene. The recombinant plasmid (BMGNeo-GCSF) was transfected into NIH/3T3 fibroblasts by the calcium phosphate coprecipitation method, and the stably transformed cells were isolated by G418 selection. An appropriate clone producing a large amount of G-CSF was selected by enzyme immunoassay of the culture supernatants. Southern blot analysis suggested that the BMGNeo-GCSF plasmid replicated mainly as an episome, and Northern blot analysis demonstrated the high expression of human G-CSF mRNA in the cells. After the implantation of the G-CSF-producing fibroblasts into nude mice, prominent neutrophilia, about 30-fold the level of normal control, was observed within seven days. Moreover, the number of hematopoietic progenitor cells in spleen remarkably increased for all cell lineages in these mice. To regulate the in vivo expression of G-CSF, we designed a subcutaneous diffusion chamber apparatus that contains the G-CSF-producing fibroblasts. The leukocytosis (neutrophilia) induced in C3H mice after embedding the device quickly disappeared after ethanol treatment of the chamber. Furthermore, reinjection of the G-CSF-producing fibroblasts into the chamber caused a second neutrophilia.
Animals↗
[Clinical analysis on the temporomandibular joints of the fifteen patients of rheumatoid arthritis].
It is seemed to be really important, when making a selection on the treatment for rheumatoid arthritis, to gain an insight into progress and activity of the disease. This analysis was taken in order to look upon the clinical symptoms and the radiographic abnormalities of the temporomandibular joints, obtained from fifteen rheumatoid arthritis patients who has visited on our department, since 1974. Ten patients (66.7%) had clinical evidences of temporomandibular joint. The most frequent symptom was pain on movement, followed by disturbances on mouth opening and crepitation. Patients who had been suffering from the disease for a long period offered more frequent clinical evidences. The acute phase symptoms, such as disturbances on mouth opening, swelling and oppressive pain in the preauricular area, was found in one patients. All of the patients showed some radiographic abnormalities. We've devised a criteria on the degree of condylar absorption on the purpose of comparison to the other abnormalities. The degree 1 was found in 3 joints, the degree 2 in 12 joints, the degree 3 in 14 joints, and the degree 4 in 7 joints. An absorption on the articular fossae and the tubercles were well along with this degrees. The higher degree the more frequent of clinical evidences in each joints was disclosed. And the period of the disease was related on the degrees, too. We can expect the bone scintigraphy by using 99mTc-MDP to be a good way for expression of the activity of the disease.
Arthritis, Rheumatoid↗
[Clinicopathological study on multiple primary malignant neoplasms, related to the oral-maxillofacial region].
The present study consists of a clinical and histopathological analysis of those cases which were diagnosed as multiple primary malignant neoplasms of the oral-maxillofacial region and the other organs. 9 patients of those multiple primary malignant neoplasms out of 261 patients of malignant neoplasms in the oral-maxillofacial region, who visited in out department from 1975 to 1986, were detected. 3.4% of the incidence rate was calculated. All the cases were male, and these included each 1 case of triple and quadruple. 7 cases were detected prior in the oral-maxillofacial region to the other organs. There seemed to be a preponderance to early detection of a neoplasm in the oral-maxillofacial region. Therefore, the possibility of multiple primary malignant neoplasms should be kept in mind in the routine clinical activities. 2 cases were synchronous, 6 months or less interval between the first and the second neoplasms, the others were metachronous, averaged 5-year interval. The primary sites in the oral-maxillofacial region were tongue (3 cases), floor of the mouth (2), buccal mucosa (2), lower gingiva (1), maxillary sinus (1), all of them were diagnosed as squamous cell carcinomas, histopathologically. The other organs were esophagus (3 cases), stomach (2), colon (2), lung (2), liver (1), urinary bladder (1), hypopharynx (1). Histopathological diagnoses of them were squamous cell carcinomas (3 cases of esophagus, each 1 case of lung, urinary bladder, and hypopharynx), adenocarcinomas (2 cases of stomach and colon, and 1 case of lung), and a hepatoma. It's necessary to differentiate the multiple primary malignant neoplasms from metastases when each of them were diagnosed as squamous cell carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Head and Neck Neoplasms↗
[Luminol-amplified chemiluminescence evaluation of the microbicidal property of alveolar macrophages in response to drugs].
The present study was designed to evaluate the validity of luminol-dependent chemiluminescence (CL) to evaluate the microbicidal properties of alveolar macrophages (AM) in response to drugs. It was observed that production of CL is associated with H2O2 as well as O2-, 1O2, .OH. Furthermore, our data revealed that CL is dependent not only upon the extracellular release of these oxygen radicals, but also upon intracellular metabolic events, which thus allows a complete analytical study in any given state. It should also be noted from our data that the effect of antibacterial agents on CL was greatly affected by the source of the target cells. The defect of amplified CL in AM obtained from young rabbits might be attributable to immaturity of AM.
Animals↗
[Clinical aspects of sarcoidosis with autoantibodies].
Among 64 sarcoidosis cases, 6 cases with autoantibodies or autoimmune disorders are described. All 6 cases were females over 40 years old, and made up 24% of the original 25 patients over 40 years old. Rheumatoid factor was observed in 2 cases, anti-DNA antibody in 4 cases and anti-microsomal antibody in 2 cases. Four cases of sarcoidosis were associated with ITP or Hashimoto's disease or rheumatoid arthritis. The presence of these autoantibodies or autoimmune diseases seemed to correlate with continued disease activity of sarcoidosis. The analysis of the clinical features of sarcoidosis with coexistent autoimmune diseases may clarify immunologic processes involved in the pathogenesis of both disorders and also provide clues to understanding the relatively poor clinical outcome of longstanding sarcoidosis.
Aged↗
Human recombinant IL-6/B cell stimulatory factor 2 augments murine antigen-specific antibody responses in vitro and in vivo.
The effects of human rIL-6/B cell stimulatory factor 2 (hrIL-6/BSF-2) from Escherichia coli on murine Ag, SRBC-specific antibody responses were examined in vitro and in vivo. HrBSF-2 was effective in augmenting the primary and the anamnestic plaque-forming cells response to SRBC in vitro. The augmentation of the primary response was apparent when B cell-enriched spleen cells (B cells) were cultured with BSF-2 in the presence of IL-2. On the other hand, hrBSF-2 alone strongly enhanced the anamnestic response in a dose-dependent manner when spleen cells from SRBC-immunized mice were used. These effects of BSF-2 were abolished completely by anti-BSF-2 antibody, but not by normal rabbit Ig. Cell depletion experiments indicated that L3T4 (CD4)+ T cells, but not Lyt-2(CD8)+ T cells, and adherent cells (macrophages) have an important role in this BSF-2-induced augmentation of the response. In addition, kinetic studies showed that hrBSF-2 acts on B cells in the anamnestic response even when added relatively late in the culture. Finally, it was determined whether BSF-2 also could be active in modulating antibody responses in vivo. BSF-2 was shown to enhance the primary and secondary antibody responses in mice. The most apparent effect of BSF-2 was observed in the secondary response.
Adjuvants, Immunologic↗
Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture.
We investigated the effects of B cell stimulatory factor 2/interleukin 6 (BSF-2/IL-6) on the development of murine hemopoietic progenitors using serum-containing culture and serum-free culture. In serum-containing culture, BSF-2 mainly supported multipotential blast cell colonies from spleen cells of normal and 5-fluorouracil (5-FU)-treated mice. In serum-free culture, no colony growth was seen in the presence of BSF-2. Addition of BSF-2 to the serum-free culture containing IL-3 resulted in a significant increase in the number of colonies formed from multipotential progenitors in spleen cells and bone marrow cells of 5-FU-treated mice, whereas no effects were seen on the number of single or oligolineage colonies formed by the spleen cells of normal mice. These results suggested that BSF-2 and IL-3 act synergistically on the multipotential progenitors but not on the maturer progenitors. When BSF-2 was added to a culture containing low concentrations of IL-3 (1 U/ml, 4 U/ml), which had little effect on colony formation, the number of total colonies formed by the spleen cells and bone marrow cells of 5-FU-treated mice increased significantly. The combination of BSF-2 and 40 U/ml of IL-3 resulted in a significant enlargement of GMM colonies. Thus, BSF-2 appears to enhance the sensitivity of multipotential hemopoietic progenitors to IL-3.
Animals↗
Autoimmune encephalomyelitis in rhesus monkeys induced by immunization with cerebral endothelial cell membrane.
It is postulated that multiple sclerosis might be an autoimmune demyelinating disease of the central nervous system (CNS). The mechanisms involved are unknown but, since the blood-brain barrier (BBB) is damaged, injury to endothelial cells is likely to have occurred. Our previous studies have led us to investigate the autoimmune effect of injuring the blood-brain barrier by immunizing rhesus monkeys with an endothelial cell membrane from the same kind of animals. The immunized animals developed a chronic or a relapsing neurological illness. Histological and ultrastructural examinations of the brain in the acute stage showed infiltrates of mononuclear cells around the blood vessels of the white matter of cerebrum, cerebellum, pons and midbrain, while in the chronic phase, large areas of demyelination and remyelination, especially in the white matter regions, were present. The animals immunized with extraneural antigen, an endothelial cell membrane obtained from human umbilical cord, developed no neurological illness. This results indicate that the brain endothelial cell membrane has an inflammatory encephalitogenic activity which could produce widespread demyelination in animals. The animal model described here may prove to be useful in the pathogenetic investigation of human autoimmune demyelinating diseases.
Animals↗
Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2).
Recombinant B cell stimulatory factor 2 (rBSF-2) did not display any detectable level of antiviral activity when using human diploid fibroblasts, DIP-2, FS-4, FS-7, amnion-derived WISH and FL cells with vesicular stomatitis virus (VSV) and Sindbis virus as challenging agents (less than 2.5 X 10(2) IU/mg). Furthermore anti-IFN-beta could not neutralize the immunoglobulin-inducing activity of BSF-2. Moreover anti-BSF-2 could not neutralize the antiviral activity of IFN-beta. The data indicate that BSF-2 is functionally and immunologically not related to IFNs.
Cross Reactions↗
High-level expression of human BSF-2/IL-6 cDNA in Escherichia coli using a new type of expression-preparation system.
BSF-2 (B cell stimulatory factor-2/IL-6) is a member of the lymphokine family and responsible for B cell differentiation. Expression plasmids of human BSF-2 cDNA were constructed using a trp promotor/operator and a trpA terminator. In an extract of Escherichia coli HB101 holding "direct" expression plasmid pBSF-2D, activity of BSF-2 was detected, but overproduction was not observed. A "fused" expression system was therefore developed to prepare the recombinant protein. In this system, cDNA was expressed as a fused protein with human IL-2 N-terminal peptide. In the case of the fused BSF-2 expression plasmid, pBSF-2F, inclusion bodies were observed and overproduction of the protein occurred. As this fused protein had a Phe-Arg-Ala sequence at the junction of hIL-2 and BSF-2, it was possible to process mature BSF-2 from the fused BSF-2 by treatment with kallikrein and aminopeptidase P. From 1 liter of E. coli culture, 45 mg of mature BSF-2 was purified; it had a relative biological activity equal to that of natural BSF-2 purified from T cells.
Amino Acid Sequence↗
[Analysis of delayed type hypersensitivity reaction of the experimental granulomatous lung--changes in Ia-positive alveolar macrophages and T-cells subsets].
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Animals↗