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1.
Clin Exp Immunol ; 168(3): 318-24, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22519595

ABSTRACT

LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1ß in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.


Subject(s)
Dermatitis, Atopic/blood , Dermatitis, Atopic/immunology , Eosinophils/drug effects , Tumor Necrosis Factor Ligand Superfamily Member 14/blood , Adult , Apoptosis/drug effects , B7-2 Antigen/genetics , B7-2 Antigen/metabolism , Biomarkers/blood , Cell Line, Tumor , Chemokine CCL17/blood , Disease Progression , Eosinophils/pathology , Female , Humans , Immunoglobulin E/blood , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Male , Middle Aged , Monocytes/drug effects , Monocytes/immunology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Necrosis Factor Ligand Superfamily Member 14/pharmacology , Up-Regulation , Young Adult
2.
Nanotechnology ; 22(11): 115704, 2011 Mar 18.
Article in English | MEDLINE | ID: mdl-21301073

ABSTRACT

We investigated a method for measuring deformation and strain distribution in a multiscale range from nanometers to millimeters via in situ FE-SEM observations. A multiscale pattern composed of a grid as well as random and nanocluster patterns was developed to measure the localized deformation at the specimen surface. Our in situ observations of a carbon fiber-reinforced polymer matrix composite with a hierarchical microstructure subjected to loading were conducted to identify local deformation behaviors at various boundaries. We measured and analyzed the multiscale deformation and strain localizations during various stages of loading.

3.
Rev Sci Instrum ; 92(11): 114705, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-34852512

ABSTRACT

This study demonstrates a high-slew-rate 5-kV pulse generator for electrical insulation tests. Electrical equipment, such as electrical actuators and traction drive motors, are exposed to severe electrical stress because recent switching inverters have high-frequency outputs with high supply voltages using wide-bandgap power devices. For an advanced electrical insulation test, a high-voltage pulse generator is required with a high slew rate; however, such generators suffer from large switching noise, followed by measurement noise, such as ground voltage fluctuations and radiation noise, hindering the detection of partial discharge (PD) phenomena. In this study, we propose a 5-kV pulse generator based on series-connected 1700-V silicon carbide (SiC) metal-oxide-semiconductor field-effect transistors (MOSFETs). Four 1700-V SiC MOSFETs are connected in series as a 5-kV SiC switching module, constituting a half-bridge configuration for the pulse generator. The obtained switching waveforms exhibit fast rise times of 48 ns under 5 kV and 6.2 ns under 400 V with a low voltage overshoot and ringing owing to superior device characteristics and reduced parasitic inductances. Because of the low switching noise, we detect a clear PD signal with a 1500-V pulse when using the fabricated pulse generator for a PD test of a twisted pair. The proposed pulse generator uses a hard switching configuration such that the pulse generator can vary the pulse width from 150 ns to DC and increase the switching pulse cycle beyond 1 MHz by changing the control signals of the SiC MOSFETs.

4.
J Exp Med ; 157(2): 583-90, 1983 Feb 01.
Article in English | MEDLINE | ID: mdl-6600487

ABSTRACT

Human T hybridomas secreting B cell growth factors (BCGF) and B cell differentiation factor (BCDF) have been established. Hybrid clones 77-A, 94-C, and 98-F secreted BCGF that induced proliferation of anti-IgM-stimulated normal B cells. The culture supernatant from 77-A cells could also maintain continuous proliferation of colony-forming B cells, but the factor from 94-C could not. The addition of the supernatant from 94-C cells to that from 77-A cells, however, synergistically augmented the proliferation of colony-forming B cells, demonstrating the existence of two distinct kinds of BCGF and the synergism between them. These supernatants, however, showed no interleukin 2 (IL-2) or BCDF activity. A hybrid clone, 90-E, secreted BCDF. The culture supernatant induced Ig production in Cowan I-stimulated normal B cells or in a transformed B cell line, CESS. However, the supernatant had no BCGF or IL-2 activity. Anti-Ig-stimulated B cells, but not IL-2-dependent T cells, absorbed BCGF activity and CESS cells absorbed BCDF activity but not BCGF activity in the culture supernatants from T hybridomas. Taken collectively, the results demonstrated that IL-2, BCGF, and BCDF were different molecules and acceptors specific for the each molecule are present on the each target cell.


Subject(s)
B-Lymphocytes/immunology , Growth Substances/pharmacology , Lymphocyte Activation , Absorption , Drug Synergism , Growth Substances/biosynthesis , Growth Substances/classification , Humans , Hybridomas/immunology , Interleukin-4 , T-Lymphocytes/immunology
5.
Nanotechnology ; 21(16): 165201, 2010 Apr 23.
Article in English | MEDLINE | ID: mdl-20348598

ABSTRACT

We study the phenomenon of change in carrier type in carbon nanotube field-effect transistors (CNFETs) caused by the atomic layer deposition (ALD) of a HfO(2) gate insulator. When a HfO(2) layer is deposited on a CNFET, the type of carrier changes from p-type to n-type. The so-obtained n-type device has good performance and stability in air. The conductivity of such a device with a channel length of 0.7 microm is 11% of the quantum conductance 4e(2)/h. The contact resistance for electron current is estimated to be 14 kOmega. The n-type conduction of this CNFET is maintained for more than 100 days. The change in carrier type is attributed to positive fixed charges introduced at the interface between the HfO(2) and SiO(2) layers. We also propose a novel technique to control the type of conduction by utilizing interface fixed charges; this technique is compatible with Si CMOS process technology.


Subject(s)
Nanotechnology/instrumentation , Nanotubes, Carbon/chemistry , Nanotubes, Carbon/ultrastructure , Transistors, Electronic , Equipment Design , Equipment Failure Analysis , Materials Testing , Static Electricity
6.
Acta Paediatr ; 99(7): 1102-4, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20219036

ABSTRACT

UNLABELLED: A 4-month-old boy was diagnosed with Kawasaki disease. The ordinary treatments with intravenous gammaglobulin and metylpredonisolone were not effective. Infliximab (5 mg/kg) was administrated on 13th day of illness which led to defeverscence and improvement of clinical manifestations. On 23 days of illness, however, desquamative papules and plaques developed on both the extensor surfaces of the forearms and legs. In addition, typical subungual desquamations of fingers and toes followed crusted hyperkeratosis which resembled supprative acrodermatitis. Skin biopsy from the forearm showed inflammatory dyskeratosis with marked hyperkeratosis, epithelial parakeratotsis, loss of granular layer and dominant infiltration of CD8 + T-cells. Local treatment of steroid followed improvement of skin lesions within a few weeks. CONCLUSION: Although previous reports described the beneficial effects of infliximab in patients with Kawasaki disease, it is possible that the administration of infliximab modify psoriasiform skin lesion associated with Kawasaki disease.


Subject(s)
Acrodermatitis/etiology , Antibodies, Monoclonal/adverse effects , Mucocutaneous Lymph Node Syndrome/drug therapy , Psoriasis/etiology , Acrodermatitis/diagnosis , Forearm/pathology , Humans , Infant , Infliximab , Male , Mucocutaneous Lymph Node Syndrome/complications , Psoriasis/diagnosis
7.
Endoscopy ; 41(1): 25-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19160155

ABSTRACT

BACKGROUND AND STUDY AIMS: Saline as an injection solution for endoscopic resection techniques has several disadvantages such as a short-lasting effect leading to a potentially higher risk of bleeding and perforation. The new substance of photocrosslinkable chitosan hydrogel in a DMEM/F12 medium (PCH) can be converted into an insoluble hydrogel by ultraviolet irradiation for 30 s, and was evaluated in two sets of animal experiments. METHODS: 18 pigs were used in the two parts of the study. First, mucosal resections were done with either PCH or hypertonic saline; the effects of both agents on wound healing were examined endoscopically and histologically. Second, in vivo degradation of PCH was examined using six pig stomachs. RESULT: PCH injection led to a longer-lasting elevation with clearer margins, compared with hypertonic saline, thus enabling precise endoscopic submucosal dissection (ESD) along the margins of the elevated mucosa. The endoscopic appearance after ESD was similar in both groups. PCH biodegradation was completed within 8 weeks according to endoscopic and histologic analyses. CONCLUSION: PCH is a promising agent for submucosal injection prior to various techniques of endoresection. It should be evaluated in clinical trials after biocompatibility testing for PCH is completed.


Subject(s)
Biocompatible Materials , Chitosan , Hydrogels/administration & dosage , Intestinal Mucosa/surgery , Wound Healing/drug effects , Animals , Biocompatible Materials/pharmacokinetics , Chitosan/pharmacokinetics , Cross-Linking Reagents , Dissection , Endoscopy , Feasibility Studies , Hydrogels/pharmacokinetics , Injections , Male , Models, Animal , Sodium Chloride/administration & dosage , Swine , Treatment Outcome
8.
Clin Exp Dermatol ; 34(6): 718-20, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19077097

ABSTRACT

Granulomatous mycosis fungoides (MF) is a rare subtype of MF, characterized by the histological presence of a granulomatous reaction, but distinct clinical characteristics are not present. A 41-year-old healthy man presented with poikiloderma, ichthyosis and erythematous scaly plaque. Histological examination of a biopsy taken from poikilodermic skin showed a granulomatous reaction to epidermotropic atypical lymphocytes. However, in other areas there were only findings of conventional MF without granuloma. Granulomatous MF may be associated with poikiloderma.


Subject(s)
Mycosis Fungoides/pathology , Rothmund-Thomson Syndrome/pathology , Skin/pathology , Adult , Biopsy , Diagnosis, Differential , Humans , Male , Mycosis Fungoides/drug therapy , Recurrence , Rothmund-Thomson Syndrome/drug therapy
9.
J Clin Invest ; 76(5): 1865-70, 1985 Nov.
Article in English | MEDLINE | ID: mdl-3932473

ABSTRACT

In an analysis of lymphocyte functions of systemic lupus erythematosus (SLE) patients, B cell abnormalities such as a lack of mitogen-responsive B cells and a predominance of spontaneous IgA-secreting cells (SC) were found. Lymphocyte functions of 20 SLE patients were studied. Impaired proliferative response to B cell mitogen, Staphylococcus aureus strain Cowan I (Cowan I), was observed, whereas the response to T cell mitogen phytohemagglutinin was normal. High levels of spontaneous IgA-SC were observed in SLE patients (greater than 10(2) cells/10(4) peripheral blood mononuclear cells [PBMC]), whereas spontaneous IgM-, IgG-, or IgE-SC were not proportionately increased. The number of spontaneous IgA-SC decreased with time in culture and became undetectable by day 5 of culture. In contrast, spontaneous immunoglobulin- (IgM, IgG, and IgA) SC were not observed in healthy volunteers (less than 10 cells/10(4) PBMC). Moreover, in SLE patients failure of induction of immunoglobulin-secreting cells (ISC) was observed when B cells were stimulated by Cowan I and B cell differentiation factor at any day tested, whereas ISC were induced in healthy volunteers on day 6 of culture. Depletion of T cells or macrophages did not affect the results obtained. These results suggest that the abnormalities observed in SLE B cells are not due to the in vitro direct effects of suppressor macrophages or suppressor T cells, and that the condition of the predominance of spontaneous IgA-SC and the unresponsiveness to exogenous stimulation may be emblematic of hyperactive B cells in SLE.


Subject(s)
Antibody-Producing Cells/immunology , B-Lymphocytes/immunology , Immunoglobulin A, Secretory/metabolism , Lupus Erythematosus, Systemic/immunology , Antigens, Differentiation, B-Lymphocyte , Antigens, Surface/immunology , Cell Differentiation , Humans , Lymphocyte Activation , Phytohemagglutinins/immunology , Staphylococcus aureus/immunology
10.
J Clin Invest ; 82(1): 316-21, 1988 Jul.
Article in English | MEDLINE | ID: mdl-2839549

ABSTRACT

Expressions and functional roles of novel IL-2 binding molecules (p70, 75) in the differentiation of B cells into Ig secreting cells were explored by using human several B cell lines and tonsillar B cells. Affinity-crosslinking studies revealed that five of nine B cell lines expressed p70 and p75 without detectable Tac antigen (p55) expression and the expression was associated with B cell maturation. In tonsillar B cells, small high-density B cells did not express p70 and p75, whereas large low-density B cells, which were thought to be activated in vivo, expressed them. Binding assays of radiolabeled IL-2 showed that the affinity of these molecules was intermediate (kD = 1-3 nM, 700-3,000 sites/cell). Furthermore, high concentrations of IL-2 (greater than 100 U/ml) induced Ig productions in large B cells and two of five cell lines. These results taken together suggest that B cells may express novel IL-2 binding molecules, associated with B cell differentiation and differentiate into Ig secreting cells by IL-2 through novel IL-2 binding molecules.


Subject(s)
B-Lymphocytes/metabolism , Interleukin-2/metabolism , Receptors, Immunologic/isolation & purification , Antigens, Surface/biosynthesis , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Cell Differentiation , Cell Line , Dose-Response Relationship, Immunologic , Humans , Immunoglobulins/biosynthesis , Interleukin-2/physiology , Kinetics , Lymphocyte Activation , Molecular Weight , Receptors, Immunologic/physiology , Receptors, Interleukin-2 , Tumor Necrosis Factor Receptor Superfamily, Member 7
11.
J Clin Invest ; 70(5): 1128-30, 1982 Nov.
Article in English | MEDLINE | ID: mdl-6290537

ABSTRACT

Bile acids in the spent medium for the cell culture were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry to determine whether human hepatoblastoma cell line could synthesize bile acids. Cholic, chenodeoxycholic, and lithocolic acids were found in the culture medium, and a portion of chenodeoxycholic acid and all of lithocholic acid were sulfated. Since the cells had been cultured in serum-free medium, it is clear that the bile acids were newly synthesized and sulfated by the cultured cells. Chenodeoxycholic acid was the main bile acid in the medium, suggesting that the cell line might predominantly synthesize chenodeoxycholic acid. On the other hand, the cells had fetal or hepatoma characters such as marked alpha-fetoprotein production. These results suggest that fetal or hepatoma type bile acid metabolism might occur in the cell line, and that the established cell line could be an useful in vitro model for the study of bile acid metabolism in hepatoma.


Subject(s)
Bile Acids and Salts/biosynthesis , Carcinoma, Hepatocellular/metabolism , Animals , Bile Acids and Salts/analysis , Carcinoma, Hepatocellular/analysis , Cell Line , Cells, Cultured , Chenodeoxycholic Acid/analysis , Chromatography, Gas , Deoxycholic Acid/analysis , Humans , Liver Neoplasms , Rats , Time Factors
12.
Nanotechnology ; 17(14): 3412-5, 2006 Jul 28.
Article in English | MEDLINE | ID: mdl-19661583

ABSTRACT

We have investigated the relation between the conduction property and the work function of the contact metal in carbon nanotube field-effect transistors (NTFETs). The conduction type and the drain current are dependent on the work function. In contrast to NTFETs with Ti and Pd contact electrodes, which showed p-type conduction behaviour, devices with Mg contact electrodes showed ambipolar characteristics and most of the devices with Ca contact electrodes showed n-type conduction behaviour. This indicates that the barrier height of the metal/nanotube contact is dependent on the work function of the contact metal, which suggests that the Fermi-level pinning is weak at the interface, in contrast to conventional semiconductors such as Si and GaAs. We have also demonstrated nonlinear rectification current-voltage characteristics in a nanotube quasi-pn diode with no impurity doping, in which different contact metals with different work functions are used for the anode and the cathode.

13.
J Natl Cancer Inst ; 78(3): 509-17, 1987 Mar.
Article in English | MEDLINE | ID: mdl-2950265

ABSTRACT

The in vivo significance of suppressor macrophages for antitumor immunity was investigated in a syngeneic tumor system. The presence of suppressor macrophages in the spleens of X5563 C3H/HeN tumor-bearing mice (TBM) was directly shown in vitro. Thus the addition of splenic macrophages of TBM suppressed the in vitro secondary induction of both tumor-specific cytotoxic T-cells and effector cells of the delayed-type hypersensitivity reaction. Splenic macrophages of TBM exerted suppression on tumor-specific T-cell-mediated cytotoxicity in the effector phase as well. Prostaglandin production was found to be one of the major mechanisms involved in macrophage-induced suppression. In vivo treatment of TBM with carrageenan and/or indomethacin retarded tumor growth and in parallel augmented cell-mediated cytotoxicity against X5563 cells, probably by affecting suppressor macrophages in vivo. The suppressive effect of splenic macrophages from TBM was clearly demonstrated in a tumor-neutralization test indicating that suppressor macrophages were able to exert their function in vivo as well as in vitro. All these results suggested that suppressor macrophages had in vivo significance for the suppression of the immunosurveillance of the hosts.


Subject(s)
Immunity, Cellular , Immunologic Surveillance , Macrophages/immunology , Neoplasms, Experimental/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Cytotoxicity, Immunologic , Immunization, Passive , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Neoplasm Transplantation , Spleen/immunology , T-Lymphocytes/immunology
14.
Cancer Res ; 49(6): 1377-82, 1989 Mar 15.
Article in English | MEDLINE | ID: mdl-2924294

ABSTRACT

We examined the effects of steroid hormones on the proliferation of transformed mouse Leydig cells (B-1) in serum-free culture condition. Among hormones examined, androgen as well as estrogen enhanced the cell proliferation rate. Hormone binding studies revealed that B-1 cells contained both androgen and estrogen receptors. In addition, androgen-enhanced cell growth was inhibited by antiandrogen, but not by antiestrogen, while estrogen-stimulated cell growth was suppressed by antiestrogen. However, the simultaneous addition of androgen and estrogen did not show an additive effect. Dose-response study on androgen-dependent cell growth revealed that relatively high concentrations (10(-7)-10(-6) M) of dihydrotestosterone were required to obtain the maximum response. This was at least partly explained by the finding that B-1 cells could metabolize dihydrotestosterone into the less active steroids. Finally, B-1 cells were found to grow more rapidly in normal than in castrated male mice. These results clearly indicate that the proliferation of B-1 cells is stimulated by both androgen and estrogen, which utilize the different receptor systems.


Subject(s)
Androgens/pharmacology , Estrogens/pharmacology , Leydig Cell Tumor/pathology , Neoplasms, Hormone-Dependent/pathology , Testicular Neoplasms/pathology , Animals , Blood Physiological Phenomena , Cell Division/drug effects , Cells, Cultured , Culture Media , Male , Mice , Mice, Inbred BALB C , Receptors, Androgen/analysis , Receptors, Androgen/physiology
15.
Cancer Res ; 44(10): 4386-91, 1984 Oct.
Article in English | MEDLINE | ID: mdl-6467199

ABSTRACT

In order to avoid the complex dual effects of estrogen and antiestrogen, the attempt was made to establish the tumor lines in which estrogens show either stimulatory or inhibitory property in terms of the tumor growth. The administration of estrogen to host mice bearing one of the mouse Leydig cell tumor lines, called T 124958-R, resulted in marked enhancement of the tumor growth even at pharmacological levels of estrogen. On the other hand, estrogenization of host mice almost completely inhibited the growth of the other tumor line (T 22137) without detectable stimulatory effects. The physiocochemical properties of the cytosol estrogen receptor in both sublines were found to be similar in relation to the affinity toward ligands, steroid specificity, sedimentation profile, and the dissociation rate kinetics. Using these tumor lines, the action mechanism of tamoxifen on the tumor growth was examined. Daily administration of this compound (30 micrograms/mouse) led to enhanced tumor growth in T 124958-R, while the growth of T 22137 was inhibited by the same procedure. In the combination experiments, tamoxifen was found to be unable to antagonize estrogen-induced enhancement or inhibition of the growth in these tumors. In addition, both tumors contained similar levels of the antiestrogen binding sites. These results suggest that tamoxifen modulated the tumor growth through its estrogenic potency.


Subject(s)
Diethylstilbestrol/pharmacology , Leydig Cell Tumor/pathology , Receptors, Drug , Tamoxifen/pharmacology , Testicular Neoplasms/pathology , Animals , Cell Division/drug effects , Cell Line , Estradiol/metabolism , Kinetics , Male , Mice , Mice, Inbred BALB C , Receptors, Estradiol , Receptors, Estrogen/metabolism , Tamoxifen/metabolism
16.
Cancer Res ; 44(1): 339-44, 1984 Jan.
Article in English | MEDLINE | ID: mdl-6317171

ABSTRACT

Two enzyme forms of alkaline phosphatase have been partially purified from the medium spent for the culture of HUH-6 clone 5 cells, which were originally derived from hepatoblastoma tissue. The purification methods used are ammonium sulfate precipitation, ethanol precipitation, diethylaminoethyl cellulose chromatography, Affi-Gel Blue chromatography, and Sephadex G-200 gel filtration. These alkaline phosphatases have been characterized by thermostability, inhibition, and immunological and electrophoretic studies. Both are L-phenylalanine and L-tryptophan sensitive and L-homoarginine and L-leucylglycylglycine insensitive, and both react with an antiserum against intestinal alkaline phosphatase. The major enzyme form is a neuraminidase-cleavable, moderately thermostable isoenzyme which on polyacrylamide gel shows an electrophoretic mobility similar to that of liver alkaline phosphatase. The minor enzyme form is a neuraminidase-uncleavable, thermolabile isoenzyme which shows an intermediate electrophoretic mobility between liver and hepatoma alkaline phosphatases. The molecular weights of the major and minor enzymes have been estimated by gel filtration to be 170,000 and 110,000, respectively. These results support the conclusion that the two enzyme forms of HUH-6 alkaline phosphatase are intestinal in type, with the major enzyme form closely resembling hepatoma and oncoamnionic alkaline phosphatases, and the minor enzyme form resembling "intestine-like liver alkaline phosphatase." HUH-6 clone 5 cell line may be a useful in vitro model to study the regulatory mechanism for phenotypic expression of intestinal-type alkaline phosphatase isoenzymes in liver cancer cells.


Subject(s)
Alkaline Phosphatase/metabolism , Carcinoma, Hepatocellular/enzymology , Intestines/enzymology , Isoenzymes/metabolism , Liver Neoplasms/enzymology , Alkaline Phosphatase/isolation & purification , Cell Line , Clone Cells , Humans , Isoenzymes/isolation & purification , Kinetics
17.
Cancer Res ; 50(16): 5060-4, 1990 Aug 15.
Article in English | MEDLINE | ID: mdl-2165854

ABSTRACT

B-1 F cells, one of the sublines established from mouse Leydig cell tumor, have been found to be maintained as an estrogen-responsive cell line under the serum-free culture conditions. Reported results that retinoids have action mechanisms similar to those of estrogen prompted us to examine the effect of retinoids on the proliferation of B-1 F cells. Stimulation of B-1 F cell growth by retinoic acid in a dose-dependent manner was observed, whereas retinoic acid did not promote but inhibited the proliferation of MCF-7 cells (estrogen- and retinoic acid receptor-positive human breast cancer cells). To elucidate the mechanism of retinoic acid-dependent cell growth, simultaneous treatment with retinoic acid and estradiol was carried out. The result did not show the additive effect on B-1 F cell growth. Hydroxytamoxifen, a potent antiestrogen, inhibited not only estradiol-dependent but also retinoic acid-dependent cell growth. However, retinoic acid failed to be associated with estrogen receptor, suggesting that retinoic acid induced enhancement of B-1 cell growth through its interaction with retinoic acid receptor. Northern blot analyses of polyadenylated RNA with complementary DNA probes for human retinoic acid receptor alpha, beta, and gamma revealed the presence of transcripts encoded by retinoic acid receptor alpha gene in B-1 F cells. These results would suggest that enhancement of the B-1 F cell growth is mediated through interaction of retinoic acid with retinoic acid receptor alpha. This stimulatory activity is inhibited by estrogen receptor complexed with hydroxytamoxifen.


Subject(s)
Estradiol/pharmacology , Tretinoin/pharmacology , Tumor Cells, Cultured/cytology , Animals , Breast Neoplasms , Carrier Proteins/genetics , Carrier Proteins/metabolism , Cell Division/drug effects , Cells, Cultured , Culture Media , DNA Probes , Female , Humans , Kinetics , Leydig Cell Tumor , Male , Mice , Neoplasm Proteins/genetics , RNA, Messenger/genetics , RNA, Messenger/isolation & purification , Receptors, Retinoic Acid , Testicular Neoplasms , Transcription, Genetic/drug effects , Tumor Cells, Cultured/drug effects
18.
Cancer Res ; 46(8): 4195-9, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3015385

ABSTRACT

The present study was performed to elucidate the differences in immune status between patients with small cell lung cancer (SCLC) and those with non-small cell lung cancer. The study group consisted of 18 patients with SCLC and 15 with non-SCLC. Two healthy volunteers and 13 patients with benign disease were also included in the present study as the non-cancer control. In the non-SCLC group, although not statistically significant, the percentages of both OKT3+ and OKT4+ T-lymphocytes in the peripheral blood lymphocytes (PBL) were slightly decreased, associated with a slight increase in the percentage of OKT8+ T-cells, and a slight decrease in the OKT4+ to OKT8+ T-cell ratio. In contrast, the PBL of the SCLC patients showed significantly lower proliferative responses to phytohemagglutinin and human recombinant interleukin 2 than did the PBL of both the SCLC patients and the noncancer control group. The ability of PBL to produce lymphokines (interleukin 2 and macrophage activating factor) was significantly impaired in the SCLC group but not in the non-SCLC group. These results suggest that suppression of helper T-cell functions and/or potentiation of suppressor T-cell functions should occur in patients with SCLC.


Subject(s)
Carcinoma, Small Cell/immunology , Lung Neoplasms/immunology , T-Lymphocytes/immunology , Adult , Aged , Antigens, Surface/analysis , Female , Humans , Immune Tolerance , Immunocompetence , Interleukin-2/analysis , Lymphocyte Activation , Lymphokines/analysis , Macrophage-Activating Factors , Male , Middle Aged , Phytohemagglutinins/pharmacology
19.
Cancer Res ; 45(4): 1663-8, 1985 Apr.
Article in English | MEDLINE | ID: mdl-3978634

ABSTRACT

Four monoclonal antibodies to MH134 murine syngeneic hepatoma cells, 3H1, 7C2, 11G2, and 12A2, were produced by hybridomas constructed by fusing P3-X63-Ag8-U1 murine myeloma cells with spleen cells of a C3H/HeN mouse immunized with the syngeneic tumor cells. Immunodiffusion analysis with rabbit anti-mouse immunoglobulin antisera showed that 3H1, 7C2, 11G2, and 12A2 are IgG2a, IgM, IgG1, and IgG2a, respectively. Enzyme-linked immunosorbent assay using cells of five syngeneic tumor lines, MH134, MM102, MM46, MM48, and X5563, and lymph node cells of C3H/HeN and C57BL/6 mice showed that 3H1 specifically bound to MH134 tumor cells, whereas 7C2, 11G2, and 12A2 reacted not only with MH134 but also with MM102 and MM46 tumor cells. None of these monoclonal antibodies bound either to cells of MM48 or X5563 tumor lines or to normal lymph node cells. These results strongly suggest that MH134 tumor cells display at least two kinds of tumor-associated antigens on their cell surfaces: one is expressed uniquely by MH134 tumor cells, which are recognized by 3H1; the other is commonly shared by MH134, MM102, and MM46 tumor cells, which are determined by the other three antibodies. 3H1, 11G2, and 12A2 but not 7C2 were found to be able to induce antibody-dependent cellular cytotoxicity (ADCC) against MH134 tumor cells. Target specificity of ADCC induced by these monoclonal antibodies was identical with that seen in enzyme-linked immunosorbent assay. 3H1, 7C2, and 12A2 but not 11G2 exhibited complement-dependent cytotoxicity, showing the same specificity in target cell lysis as that seen in enzyme-linked immunosorbent assay or ADCC. Pretreatment of MH134 tumor cells with 7C2 inhibited ADCC of both 11G2 and 12A2. Pretreatment of the tumor cells with 11G2 inhibited complement-dependent cytotoxicity of both 7C2 and 12A2. Neither ADCC nor complement-dependent cytotoxicity of 3H1 was inhibited by the pretreatment of the cells with 7C2 or 11G2. These results strongly suggest that tumor-associated antigens recognized by 3H1 are located apart from that recognized by 7C2, 11G2, and 12A2 and that the binding sites of the latter three antibodies are closely associated with, or identical with, each other in the tumor-associated antigen. The ability of 12A2 to induce ADCC against MH134 tumor cells was significantly stronger than that of 3H1 or 11G2.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Antibodies, Monoclonal/immunology , Antibody-Dependent Cell Cytotoxicity , Macrophages/immunology , Neoplasms, Experimental/immunology , Animals , Complement System Proteins/immunology , Enzyme-Linked Immunosorbent Assay , Immunotherapy , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Neoplasms, Experimental/therapy
20.
Cancer Res ; 46(3): 1047-54, 1986 Mar.
Article in English | MEDLINE | ID: mdl-3510719

ABSTRACT

The in vivo antitumor effect of i.p. injection of allogeneic spleen cells was investigated. ACl rats were inoculated i.p. with 10(4) AMC-60 syngeneic fibrosarcoma cells and given injections i.p. of 4 X 10(7) Wistar spleen cells once a week for 3 wk from 1 day after tumor inoculation. This treatment significantly prolonged the survival period of the tumor-bearing rats. A similar effect was obtained by i.p. injections of Lewis spleen cells. Injection i.p. into ACl rats of spleen cells of these rat strains resulted in the apparent augmentation of cytolytic activity of peritoneal adherent but not of nonadherent cells against AMC-60 tumor cells. The cytotoxicity was exhibited nonspecifically to cells of a variety of tumor lines but not to concanavalin A blasts of ACl spleen cells and was inhibited by the addition of carrageenan. Irradiation (2000 R) of Lewis spleen cells or fractionation of the allogeneic spleen cells using nylon wool columns revealed that a radiosensitive and nylon wool-passed cell population, presumably a T-cell population, of the allogeneic spleen cells is responsible for the augmentation of peritoneal macrophage tumoricidal activity in ACl rats. Further, Lewis spleen cells irradiated at 2000 R neither augmented peritoneal macrophage cytotoxicity nor prolonged the survival period of ACl rats bearing AMC-60 tumor, suggesting that the augmentation of peritoneal macrophage cytotoxicity plays a major role in the in vivo antitumor effect of the allogeneic spleen cell transfer. ACl rats were given injections i.p. of 4 X 10(7) Lewis spleen cells. Two days after injection, cells including peritoneal cells of the ACl rats and Lewis spleen cells remaining in the peritoneal cavities were obtained by peritoneal lavages and then incubated for 5 days. Significant blastogenic proliferation was observed, and the supernatant of the culture was shown to be able to render thioglycollate-induced peritoneal macrophages of ACl rats cytotoxic to AMC-60 tumor cells, indicating that a certain cell population of the cell mixture produced a lymphokine(s) resembling macrophage activating factor (MAF) during the incubation. When ACl rats were given injections i.p. of irradiated Lewis spleen cells, neither the blastogenic proliferation nor the generation of MAF activity in the culture supernatant was observed. Indirect immunofluorescence analysis using rabbit anti-ACl and anti-Lewis antisera revealed that as many irradiated Lewis spleen cells were remaining in the peritoneal cavities as normal Lewis spleen cells 2 days after injection into ACl rats.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Macrophages/immunology , Sarcoma, Experimental/therapy , Spleen/immunology , Animals , Cells, Cultured , Cytotoxicity, Immunologic , Fibrosarcoma/therapy , Immunotherapy , Lymphokines/biosynthesis , Macrophage Activation , Macrophage-Activating Factors , Male , Rats , Rats, Inbred Strains , Sarcoma, Experimental/immunology
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