When cells are exposed to low doses of a mutagenic or clastogenic agents. they often become less sensitive to the effects of a higher dose administered subsequently. Such adaptive responses were first described in Escherichia coli and mammalian cells to low doses of an alkylating agent. Since most of the studies have been carried out with human lymphocytes, it is urgently necessary to study this effect in different cellular systems. Its relation with inherent cellular radiosensitivity and underlying mechanism also remain to be answered. In this study, adaptive response by 1 cGy of gamma rays was investigated in three human lymphoblastoid cell lines which were derived from ataxia telangiectasia homozygote, ataxia telangiectasia heterozygote, and normal individual. Experiments were carried out by delivering 1 cGy followed by 50 cGy of gamma radiation and chromatid breaks were scored as an endpoint. The results indicate that prior exposure to 1 cGy of gamma rays reduces the number of chromatid breaks induced by subsequent higher dose (50 cGy), The expression of this adaptive response was similar among three cell lines despite of their different radiosensitivity. When 3-aminobenzamide, an inhibitor of poly (ADP-ribose) polymerase, was added after 50 cGy, adaptive responses were abolished in all the tested cell lines. Therefore it is suggested that the adaptive response can be observed in human lymphoblastoid cell lines, which was first documented through this study. The expression of adaptive response was similar among the cell lines regardless of their radiosensitivity. The elimination of the adaptive response by 3-aminobenzamide is consistent with the proposal that this adaptive response is the result of the induction of a certain chromosomal repair mechanism.
Shon K. S.;Kwon O. S.;Min B. J.;Cho J. H.;Chen Y. J.;Kim I. H.;Kim H. S.
Korean Journal of Poultry Science
/
v.31
no.4
/
pp.237-244
/
2004
This study was conducted to investigate the effects of dietary Animunin Powder$^{?}$ on the egg quality characteristics, blood components and nutrient digestibility in laying hens. A total of two hundred seventy laying hens were randomly allocated into three treaments with fifteen replications for eight weeks. Dietary treaments included 1) Control (CON), 2) Control + $0.1\%$ Animunin Powder$^{?}$ (AM1), 3) Control + $0.2\%$ Animunin Powder$^{?}$ (AM2). During the period of 0~4weeks, the birds fed the AM1 diet had an improved egg production compared to the birds fed the CON (P<0.05). During the period of 4~8weeks the birds fed AM1 diet showed a statistically improved egg production compared to the CON (P<0.05). However, no significant differences were founded in the egg weight. During the period of $4\~8$ weeks the hens fed the AM2 diet had improved egg yolk color compared to the hens fed CON and AM1 diets (P<0.05). In the Haugh unit for the period of $0~4$$weeks, the AM2 treatment showed significantly improved results compared to the CON (P<0.05). Average egg shell breaking showed no significant differences through the experiment period, but in the period of $4\~8$weeks the AM2 treatment tended to be improved compared to the CON and AM1 treatment (P<0.05). There was no significant differences in egg shell thickness. In the serum cholesterol, the AM1 and AM2 treatments were significantly lower than the CON (P<0.05). The concentration of RBC and WBC in the AM treatments tended to increase but there were no significant differences. For the differences of lymphocytes between the end and initiation of the experiment, the hens fed the AM1 treatment were significantly different compared to the hens fed the CON and AM2 treatment (P<0.05). During the period of the experiment, the hens fed the AM1 diet were tended to show higher DM digestibility than the hens fed the CON and AM2 diet, but it was not statistically different. In conclusion, dieatry fed of Animunin Powder$^{?}$ could improve egg production, egg yolk color, and haugh unit.
Purpose : Fragile sites are points on chromosomes which tend to break non-randomly when exposed to specific chemical agents or conditions of tissue culture. The chromosomal break induced by the antineoplastic drug, 1-${\beta}$-D-arabinofuranosyl-cytosine(Ara-c), was investigated to study the laboratory conditions in which the incidence of chromosomal break could be enhanced. Besides, the fragile sites induced by Ara-C were investigated and compared to the already known locations of the specific chromosomal alterations observed in specific neoplasms. Methods : T-lymphocytes from theree normal males and three females were cultured for 48 hours. Cells from each individual were exposed to the Ara-C for an additional 24 hours. After the caffeine was added during the last six hours culture, the metaphase chromosomes were prepared following the conventional method. A site was considered fragile if it was found to break two or more per 100 chromosomal breaks in more than four of six individuals tested. Results : Ara-C induced 252.1 chromosomal breaks per 100 mitotic cells and this result was significantly higher than that of the control, which induced 25.2 breaks(P<0.05). The incidence of the chromosomal break by Ara-C was higher, if cultured in the MEM-FA, which has no folic acid, than in the RPMI 1640 which contains enough folic acid(P<0.05). The most common break site by Ara-C was 3p14.2(FRA3B). There were 20 fragile sites induced by Ara-C. Among these 20 fragile sites, seven coincided with the locations of the mapped oncogenes, JUN, SKI, REL, N-MYC, FHIT, MET, ETS-1, and FOS. Conclusion : S phase specific chemotherapeutic agent, Ara-C, induced the expression of the chromosomal fragile sites effectively using the T-lymphocyte in vitro. Some of the fragile sites by Ara-C highly coincided with the oncogenes and neoplasm specific chromosome breakpoints. In this regard, the fragile sites reported here could provide the unknown neoplasm related chromosomal alternation points.
Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.
An experiment was conducted to investigate the effects of dietary acidifier($Lactacid^(R)$) and essential oil($Immunocin^(R)$) on the performance, nutrient metabolizability, small intestinal microflora, IgG level and leukocytes and erythrocytes in broiler chickens. Five hundred males and 500 females broiler chickens($Ross^(R)$) were divided into 20 pens of 50 chickens(25 birds in each sex). Five pens were assigned to each of four dietary treatments: control, diets containing antibiotics(Bacitracin methylene disalicilate), acidifier($Lactacid^(R)$) and essential oil($Immunocin^(R)$) dietary treatments. Birds were fed experimental diets ad libitum 5 wks. Weight gain, feed intake, and feed conversion rate were significantly affected by dietary treatment(P<0.05). Overall weight gain($0{\sim}5$ wks) of $Lactacid^(R)$ treatment was significantly lower than the others. Feed intake was highest(P<0.05) in the control followed by antibiotics, $Lactacid^(R)\;and\;Immunocin^(R)$ treatment. Feed conversion rate of $Immunocin^(R)$ treatment was lowest(P<0.05) followed by antibiotics, $Lactacid^(R)$ treatment and the control. Production indices of $Immunocin^(R)$ and antibiotics treatments were significantly higher than those of the control and $Lactacid^(R)$ treatment(P<0.05). $Immunocin^(R)$ treatment was the highest and antibiotics was lowest in serum IgG level. The number of leukocytes and stress index(neutrophil/lymphocytes) tended to be lower in $Immunocin^(R)$ treatment than others. There were no significant differences in erythrocytes among the treatments. The cfu of E. coli was significantly lower in $Immunocin^(R)$ and antibiotics treatments than $Lactacid^(R)$ treatment and the control. Metabolizability of crude protein was significantly lower in the control than $Lactacid^(R)\;and\;Immunocin^(R)$ treatment while that of NFE was significantly lower in $Immunocin^(R)\;than\;Lactacid^(R)$ and antibiotics treatments. It was concluded that essential oil product $Immunocin^(R)$ is as effective as antibiotics in improving feed conversion efficiency and production index while $Lactacid^(R)$ is not.
Kim, Myung-Jae;Kim, Noe-Kyeong;Lee, Jung-Sang;Choi, Keun-Chul;Lee, Ryong-Woo;Kim, Kee-Won;Kang, Shin-Il
The Korean Journal of Nuclear Medicine
/
v.3
no.1
/
pp.51-58
/
1969
To clarify the hematologic effects of the radioiodine ($^{131}I$) in therapeutic doses ($5{\sim}10$ mCi) on the various thyroid patients, authors studied the peripheral blood pictures of 396 goitrous patients before and after radioiodine ($^{131}I$) administrations in the Isotope Clinic of Seoul National University Hospital. Among these 396 cases of goiters, we gave 5 to 10 mCi of radioiodine ($^{131}I$) with single or fractionated administrations. The blood pictures of peripheral blood were repeated after 3 months in 40 cases of 65 cases who had been treated with $^{131}I$. The blood pictures of non-treated thyroid patients were compared with that of normal Korean values to clarify any difference between normal and goiter. The blood pictures of hyperthyroid patients treated with $^{131}I$ therapy were compared with the blood pictures of non-treated thyroid patients. The results were as following: 1) The incidence according to type: Toxic diffuse goiter: 35.4% Nontoxic nodular goiter: 29.7% Euthyroid: 13.8% Nontoxic diffuse goiter: 12.6% Hypothyroidism: 4.3% Thyroiditis($\bar{s}$ subacute form): 1.8% Toxic nodular goiter: 1.4% Malignancy: 1.0% 2) Age incidence: The range of distribution was 11 to 71 years. The peak incidence was found in the 4th decade of life. $80.6{\sim}82.6%$ of those 396 cases were found among the 3rd, 4th and the 5th decades of life. 3) Sex incidence: Sex ratio of male:female was 1:7.8. 4) The most outstanding findings in peripheral blood before treatment were decreased erythrocyte count and hemoglobin value in all types of thyroid diseases, especially in. the cases of hypothyroidism and thyroiditis. Hook worm-infested patients showed no significant difference in erythrocytes and hemoglobin values from those of other hook worm free patients. 5) Total leukocytes count was within normal range. Differential count of W.B.C. showed increased percentile of lymphocyte in diffuse toxic goiter and thyroiditis. 6) 39 cases of diffuse goiter treated with $^{131}I$ toxic showed amelioration in the anemia and restoration to normal range of lymphocyte count in association with increased percentile of neutrophiles 3 months after administration, except a case of toxic nodular goiter. One can observe anemia in slight degree, and increased lymphocytes count in hypothyroidism. Therapeutic dose of radioiodine ($^{131}I$) does not result any residual effect on the hematopoietic function. Radioiodine ($^{131}I$) therapy resulted in improvement of thyroid function in association of amelioration of pevious abnormal blood pictures. 7) Authors did not observe any myxedema resulted from radioiodine therapy during the 3 months period in this study.
This experiment was performed to evaluate the morphological responses of the duodenal epithelial cells of the mouse, inoculated with Ehrlich carcinoma cells in the inguinal area, following administration of Bacillus Calmette-Guerin (BCG). In the experimental groups, each mouse was inoculated with $1{\times}10^7$ Ehrlich carcinoma cells subcutaneously in the inguinal area. From next day after inoculations, 0.2 mL of saline or BCG (0.5 mL/25 g B.W.: $0.03{\times}10^8\sim0.32{\times}10^8$ CFU) were injected subcutaneously to the animals every other day, respectively. The day following the 7th injection of saline or BCG, each mouse was injected with a single dose of $0.7{\mu}Ci$/g of methyl-$^3H$-thymidine (25 Ci/mmol, Amersham Lab, England) through tail vein. Seventy minutes after the thymidine injection, animals were sacrificed, and duodenal tissues were taken and fixed in 10% neutral formalin. Deparaffinized sections were coated with autoradiographic emulsion EM-1 (Amersham Lab, England) in a dark room and dried and were placed in a light-tight box. The number of labeled epithelial cells in the duodenal mucosae (mean number of labeled epithelial cells per 3.5 mm length of mucosa) were observed and calculated. On the light microscopic study, duodenal mucosae had no severe morphological changes following the injection of BCG. In the tumor control and BCG treated groups, a number of small lymphocytes and eosinophile leucocytes are slightly increased as compared with those of the normal control ones. On the autoradiographic study, number of the labeled cells of normal control, tumor control and BCG-treated mice were 632.3 (${\pm}14.47$), 761.7 (${\pm}27.65$) and 505.0 (${\pm}17.09$) respectively. From the above results, BCG may suppress the DNA synthesis of the duodenal epithelial cells, but does not results severe structural defect on the duodenal mucosae. And it is suggested that BCG may greatly improve the anticancer therapy on certain kind of cancer.
Atopic dermatitis (AD) is characterized by chronic relapsing inflammation and is associated with hyper-production of immunoglobulin E (IgE). Recent studies have suggested that one of the treatments to alleviate symptoms of AD could be a supplementation of probiotics, Lactobacillus, Rhamnosus, Bifidus, etc. The purpose of this study was to evaluate the effects of probiotics on immune parameters in NC/Nga mice treated with 1-chloro-2,4-dinitro-benzene (DNCB). To induce atopic dermatitis, DNCB was treated to the back of mice for 2 weeks. Then, NC/Nga mice were divided into the four experimental groups randomly. Probiotics fragment, probiotics with other complex (Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12LbL, L. plantarum K8, L. plantarum K8 fragment, ${\gamma}$-linolenic acid), antihistamine, and distilled water were administrated orally to the NC/Nga mouse for 4 weeks of experimental period. The groups were probiotics fragment group (DPF), probiotics with other complex group (DPOC), antihistamine group (DAH) and distilled water group (DDW) as a control group. The levels of serum IgE, interlukin-4 (IL-4), interlukin-5 (IL-5), interferon-gamma (IFN-${\gamma}$) and spleenocyte IgE were measured. The levels of serum IgE were significantly different among the four experimental groups. Before the treatment, there was no differences among the groups. However, from the first through the third week of the treatments, the levels of serum IgE in the probiotics (DPF, DPOC) and antihistamine (DAH) groups were lower than those of control group (p < 0.05). The levels of serum IL-4 of DPOC group was significantly lower than that of control group (p < 0.05) and serum IL-5 levels of DPF, DPOC, and DAH groups were significantly lower than that of control group. The levels of serum IFN-${\gamma}$ were not different among the four experimental groups. The levels of serum IgE in supernatant of spleen lymphocytes were not significantly different among the groups. These results suggest that probiotics supplementation showed partial effectiveness in the DNCB treated NC/Nga mice via modulation of IgE level and IL-4, IL-5 production. Based on these findings, probiotics exhibited the inhibitory effect via IL-4 production thereby inhibited the production of IgE in atopic animal model NC/Nga mice.
In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.
Background: Interferon-$\gamma$ has various biologic effects, including antiviral effect, antitumor proliferative effect, activation of macrophage and B lymphocyte, and increased expression of major histocompatibility complex. Especially, antitumor proliferative effect of interferon-$\gamma$ has already been proved to be important in vivo as well as in vitro. And, clinical studies of interferon-$\gamma$ have been tried in lung cancer patients. However, the mechanism of antitumor effect of interferon-$\gamma$ has not yet been established despite of many hypotheses. "Necrosis" is a type of cell death which is well known to occur in the circumstances of severe stresses. In contrast, "apoptosis" is another type of cell death which occurs in such biological circumstances as embryonic development, regression of organs, and self-tolerance of lymphocytes. And, apoptosis is an active process of cell death in which cells are dying with fragmentations of their cytoplasms and nuclei. And, in the process of apoptosis the DNAs of cells are cleaved between nucleosomes by unidentified endonuclease and therefore DNAs of apoptotic cells result in a typical electrophoresis pattern known as DNA ladder pattern. Recently it has been suggested that cytotoxic effect of interferon-$\gamma$ occurs via apoptosis. To elucidate the mechanism of antitumor cytotoxic effect of interferon-$\gamma$, we microscopically observed a lung cancer cell line, A549 which was treated with interferon-$\gamma$. We observed A545 treated with interferon-$\gamma$ was dying fragmented. And so, we performed this study to find out that the mechanism of antitumor cytotoxic effect of interferon-$\gamma$ be apoptosis. Method: We treated A549, human lung cancer cell line with various concentration of interferon-$\gamma$ and quantified its cytotoxic effect of various periods, 24 hours, 72 hours and, 120 hours by MTT(dimethylthiazolyl diphenyltetrazolium bromide) bioassay. Also, after we treated A549 with 100 units/mi of interferon-$\gamma$ for 120 hours, we observed the pattern of cell death with inverted microscope and we extracted DNAs from the dead A549 cells and observed the pattern of 1.5% agarose gel electrophoresis with ethidium bromide staining. Result: 1) Cytotoxic effect of interferon-$\gamma$ on A549: For the first 24 hours, threre was little cytotoxic effect and for between 24 hours and 72 hours, there was the beginning of cytotoxic effect and for 120 hours there was increased cytotoxic effect. 2) Pattern of A549 cell death by interferon-$\gamma$: We observed with inverted microscope that A549 cells were dying fragmented. 3) DNA ladder pattern of gel electrophoresis: We observed DNA ladder pattern of gel electrophoresis of extracted DNAs from dead A549 cells. Conclusion: We concluded that the mechanism of interferon-$\gamma$induced cytotoxicity on lung cancer cell line, A549 be via apoptosis.
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