• IMMUNE NETWORK
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• v.2 no.2
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• pp.102-108
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• 2002

Background: This study was aimed to differentiate two forms of CTLA-4 (CD152) in activated peripheral blood lymphocyte and clarify the mechanism how cytoplasmic form of this molecule is targeted to cell surface. Methods: For this purpose we generated 2 different anti-human CD152 peptide antibodies and 5 different N'-terminal deletion mutant CTLA4Ig fusion proteins and carried out a series of Western blot and ELISA analyses. Antipeptide antibodies made in this study were anti-CTLA4pB and anti-CTLA4pN. The former recognized a region on extracellular single V-like domain and the latter recognized N'-terminal sequence of leader domain of human CD152. Results: In Western blot, the former antibody recognized recombinant human CTLA4Ig fusion protein as an antigen. And this recognition was completely blocked by preincubating antipeptide antibody with the peptide used for the antibody generation at the peptide concentration of 200 ug/ml. These antibodies were recognized human CD152 as a cytoplasmic sequestered- and a membrane bound- forms in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocyte (PBL). These two forms of CD152 were further differentiated by using anti-CTLA4pN and anti-CTLA4pB antibodies such that former recognized cytosolic form only while latter recognized both cytoplasmic- and membraneforms of this molecule. Furthermore, in a transfection expression study of 5 different N'-terminal deletion mutant CTLA4Ig, mutated proteins were secreted out from transfected cell surface only when more than 6 amino acids from N'-terminal were deleted. Conclusion: Our results implies that cytosolic form of CTLA-4 has leader sequence while membrane form of this molecule does not. And also suggested is that at least N'-terminal 6 amino acid residues of human CTLA-4 are required for regulation of targeting this molecule from cytosolic- to membrane- area of activated human peripheral blood T lymphocyte.

• Environmental Mutagens and Carcinogens
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• v.22 no.3
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• pp.142-148
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• 2002

Although ionizing radiation (IR) has been used to treat the various human cancers, IR is cytotoxic not only to cancer cells but to the adjacent normal tissue. Since normal tissue complications are the limiting factor of cancer radiotherapy, one of the major concerns of IR therapy is to maximize the cancer cell killing and to minimize the toxic side effects on the adjacent normal tissue. As an attempt to develop a method to monitor the degree of radiation exposure to normal tissues during radiotherapy, we investigated the transcriptional responses of human peripheral blood lymphocytes (PBL) following IR using cDNA microarray chip containing 1,221 (1.2 K) known genes. Since conventional radiotherapy is delivered at about 24 h intervals at 180 to 300 cGy/day, we analyzed the transcriptional responses ex-vivo irradiated human PBL at 200 cGy for 24 h-period. We observed and report on 1) a group of genes transiently induced early after IR at 2 h, 2) of genes induced after IR at 6 h, 3) of genes induced after IR at 24 h and on 4) a group of genes whose expression patters were not changed after IR. Since Biological consequences of IR involve generation of various reactive oxygen species (ROS) and thus oxidative stress induced by the ROS is known to damage normal tissues during radiotherapy, we further tested the temporal expression profiles of genes involved in ROS modulation by RT-PCR. Specific changes of 6 antioxidant genes were identified in irradiated PBL among 9 genes tested. Our results suggest the potential of monitoring post-radiotherapy changes in temporal expression profiles of a specific set of genes as a measure of radiation effects on normal tissues. This type of approach should yield more useful information when validated in in vivo irradiated PBL from the cancer patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1179-1185
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• 2004

The Korean traditional medicine, Seonghyangjeonggisan (SHJGS) has long been used for acute cerebral infarction (Cl). However, scientific investigation has been carried out a little. Cytokines, involved in the regulation of inflammatory reactions and immune responses, may play an important role in the pathogenesis of Cl. The aim of this study is to investigate the effects of SHJGS on the production of various cytokines in the patients with acute Cl. Peripheral blood mononuclear cells (PBMC) obtained from the patients with acute Cl were cultured for 24hr in the presence or absence of lipopolysaccharide (LPS) and phytohaemagglutinin (PHA). The amount of TNF-α, IL-1β, IL-6 and IL-8, in PBMC culture supernatant, was significantly increased in the LPS and PHA treated cells, compared with unstimulated cells (P<0.05). This study showed that increased TNF-α, IL-1β, IL-6 and IL-8 level stimulated by LPS and PHA was inhibited by SHJGS (0.01-1 ㎎/㎖) in a dose-dependent manner but IL-8 level was not inhibited significantly at 1㎎/㎖ (P>0.05). The maximal inhibition rate of TNF-α, IL-1β, IL-6 and IL-8 by SHJGS (1㎎/㎖) was 68% (P<0.05), 53.9% (P<0.05), 45.5% (P<0.05), 46.7% (P>0.05) respectively. These results suggest that SHJGS might have anti-inflammatory effects through cytokine modulation. which might explain its beneficial effects in the treatment of acute Cl.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.14 no.1
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• pp.129-153
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• 2001

Background: SMG (升麻葛根湯加味方) is an herbal medicine which has been used in oriental medicine as a traditional therapeutic agent of pruritus and skin disease. Objective: This study was performed to investigate the effect of SMG on the anti-hypersensitivity and immune response in the murine of type I hypersensitivity induced by the experiment. Materials and Methods: Laboratory rats were primary sensitized with OA (ovalbumin); on day 1, rats of a Control group and Sample group (SMG group) were systemically immunized by subcutaneous injection of 1mg OA and 300mg of Al(OH)3 in a total volume of 2ml saline. The rats of the sample group were orally administered with an SMG water extract for 14 days after primary immunization. On day 14 after the systemic immunization, rats received local immunization by inhaling $0.9\%$ saline aerosol containing $2\%$(wt/vol) OA. A day after local immunization, BAL fluid and peripheral blood were collected from the rats. Total cell, lymphocyte, $CD4^+\;T\;cell,\;CD8^+\;T\;cell,\;CD4^+/CD8^+$ ratio in the BALF, and IgE, $CD4^+\;T\;cell,\;CD8^+$ T cell in the peripheral blood were measured and evaluated. Results: SMG showed a suppressive effect on the immune response in the rats. 1. Total Cells in the BALF decreased in the SMG treated group in comparison group, but statistic differences were not observed. 2. Total lymphocytes in the BALF were statistically decreased in SMG treated group in comparison to the control group. 3. CD4+ T cells in the BALF were statistically decreased in SMG treated group in comparison to the control group. 4. CD8+ T cells in the BALF were decreased in SMG treated group in comparison to the control group, but statistic differences were not observed. 5. The ratio of CD4+/CD8+ in the BALF was statistically decreased in SMG treated group in comparison to the control group. 6. The IgE level in serum was statistically decreased in SMG treated group in comparison to the control group. 7. The ratio of CD4+ and CD8+ in peripheral blood showed undetectable differences between each group of rats. From the experiment cited above, this study shows that SMG has both anti-hypersensitivity effects and immunoregulatory effects when administered to rats. Based on this experiment, it is suggested that SMG could be a useful immunomodulator and anti-allergy agent.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.21 no.10
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• pp.127-136
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• 2020

Purpose: This study aimed to establish a basis for application time and cold therapy interval by checking the physiological changes after applying a cold-gel and ice pack, commonly applied to cold therapy, and after passive rewarming. Method: A total of 22 healthy adults used cold-gel packs and ice packs in a Randomized control group repeated measurement study, and passive rewarming was performed for 40 minutes after 30 minutes of cold therapy. After applying to the right axilla, StO₂, SpO₂, peripheral blood flow, skin and body temperature were measured 15 times every 5 minutes. Result: In the cold-gel pack group, StO₂ decreased from 69.43% to 61.06% after 30 minutes application, and in the ice pack group, StO₂ decreased from 67.66% to 64.80% (p <001). In the cold-gel pack group, skin temperature decreased from 33.57℃ to 29.15℃ after 30 minutes application, and in the ice pack group, skin temperature decreased from 32.64℃ to 28.90℃ (p <.001). Only skin temperature recovered completely after 40 minutes of rewarming. There were insignificant differences between the cold-gel pack and ice pack. Conclusion: When applying cold therapy to the axillary, at least 40 minutes for passive rewarming is necessary after 30 minutes of application.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.368-376
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• 2014

BACKGROUND/OBJECTIVES: The objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs. MATERIALS/METHODS: Mononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and $50{\mu}g/mL$ of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK. RESULTS: The proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and $50{\mu}g/mL$ of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury. CONCLUSIONS: Lycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

• Journal of Veterinary Clinics
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• v.28 no.2
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• pp.183-189
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• 2011

The objective of this study was to examine the effect of fucoidan on the phagocytic capapcity and oxidative burst activity (OBA) of canine peripheral blood polymorphonuclear cells (PMNs). The phagocytic capacity and OBA of PMNs were evaluated simultaneously by using a flow cytometer. Fucoidan itself did not cause any direct effect on the phagocytic capacity and OBA of PMNs. However, the phagocytic capacity and OBA of PMNs were enhanced by the culture supernatant from PBMCs treated with fucoidan. The phagocytic capacity and OBA of PMNs were also increased by treatment with recombinant canine (rc) tumor necrosis factor (TNF)-${\alpha}$. The ability of the culture supernatant from fucoidan-treated PBMCs to stimulate the phagocytic capacity and OBA of PMNs was inhibited by addition of anti-rc TNF-${\alpha}$ polyclonal antibody (PAb) prior to the culture. The amount of TNF-${\alpha}$ in the culture supematant from PBMCs was shown to increase upon treatment of fucoidan as compared with that of vehicle-treated PBMCs culture supematant. The level of TNF-${\alpha}$ mRNA expression in PBMCs was also up-regulated by the fucoidan treatment. These results suggest that fucoidan has an immunoenhancing effect on the phagocytic capacity and OBA of canine PMNs, which is mainly mediated by TNF-${\alpha}$ released from fucoidan-stimulated PBMCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.5
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• pp.341-347
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• 2020

Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck cancer. MicroRNAs, as new biomarkers, are recommended for diagnosis and treatment of different types of cancers. Bevacizumab, sold under the trade name Avastin, is a humanized whole monoclonal antibody that targets and blocks VEGF-A (vascular endothelial growth factor A; angiogenesis) and oncogenic signaling pathways. Materials and Methods: This study comprised 50 cases suffering from OSCC and 50 healthy participants. Peripheral blood samples were collected in glass test tubes, and RNA extraction was started immediately. Expression levels of miR-155, miR-191, and miR-494 biomarkers in the peripheral blood of OSCC-affected individuals and healthy volunteers in vivo were evaluated using real-time PCR. The influence of Avastin on the expression levels of the aforementioned biomarkers in vitro and in the HN5 cell line was also investigated. Results: Expression levels of miR-155, miR-191, and miR-494 in the peripheral blood of individuals affected by OSCC were higher than in those who were healthy. Moreover, Avastin at a concentration of 400 μM caused a decrease in the expression levels of the three biomarkers and a 1.5-fold, 3.5-fold, and 4-fold increase in apoptosis in the test samples compared to the controls in the HN5 cell line after 24, 48, and 72 hours, respectively. Conclusion: The findings of this study demonstrate that overexpression of miR-155, miR-191, and miR-494 is associated with OSCC, and Avastin is able to regulate and downregulate the expression of those biomarkers and increase apoptosis in cancerous cells in the HN5 cell line.

• The Korean Journal of Nuclear Medicine
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• v.3 no.1
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• pp.51-58
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• 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.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.171-177
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• 2020

Objective : To evaluate the neuroprotective effects of lacosamide after experimental peripheral nerve injury in rats. Methods : A total of 28 male wistar albino rats weighing 300-350 g were divided into four groups. In group I, the sciatic nerve exposed and the surgical wound was closed without injury; in group II, peripheral nerve injuries (PNI) was performed after dissection of the nerve; in group III, PNI was performed after dissection and lacosamide was administered, and in group IV, PNI was performed after dissection and physiological saline solution was administered. At 7 days after the injury all animals were sacrificed after walking track analysis. A 5 mL blood sample was drawn for biochemical analysis, and sciatic nerve tissues were removed for histopathological examination. Results : There is low tissue damage in lacosamide treated group and antioxidant anzymes and malondialdehyde levels were higher than non-treated and placebo treated group. However there was no improvement on clinical assessment. Conclusıon : The biochemical and histological analyses revealed that lacosamide has neuroprotective effect in PNI in rats. This neuroprotective capacity depends on its scavenger role for free oxygen radicals by increasing antioxidant enzyme activity.