• Korean Journal of Veterinary Research
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• v.1 no.1
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• pp.1-29
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• 1961

A routine hematological observation in the course of starvation was carried out on eight experimentel1y starved rabbits. They were strictly selected and restricted all of food intake with the exception of optional water intake until death. The body weight of each rabbit on the day before starvation was about 2 kilograms. The results are summarized as follows. 1. The average decrememt ratio of body weight on the terminal day before death was $34.3{\pm}7.5$ per cent with the range from 24.5 to 46.3 per cent. The average life duration until death was $10.25{\pm}2.6$ days, the range being from 6 to 14 days. 2. The decrease in number of reticulocytes with a parallel disappearance of polychromatic erythrocytes in peripheral blood in the course of starvation Was the most remarkable change in erythrocytic series, an evidence suggesting marked restriction of the erythropoietic function on 3rd to 4th day and almost complete suspension in about a week of starvation. 3. Erythrocyte count, hemoglobin content and haematocrit value of peripheral blood, were normal or indicative of slight hemoconcentration. 4. Mean Corpuscular Hemogloin Concentration was slightly higher than normal and Mean Corpuscular Volume tended to be low and no appreciable shifts were observed in Mean Corpuscular Diameter and Price-Jones curve of erythrocytes, while fewer macrocytes than normal were seen. These changes were considered to have resulted from a marked decrease in young erythrocytes in peripheral blood in the course of starvation. 5. Neither poikilccytoses or anisosytosis was observed. 6. Leukopenia was observed in all of 8 starved rabbits. The decrement ratio on the terminal day of starvation was between 13 to 64 per cent. The leukopenia was mainly due to fall of lymphocytes in 6 cases and to fall of neutrophilic leukocytes in the other 2 cases. In many cases, irregular fluctuation of neutrophilic leukocytes in its biological curve were seen in contrast to the relatively smooth changes of lymphocytes. Eosinophilic leukocytes tended to decrease in absolute number especially in later stage of starvation. Little significance in regard to monocytes and basophilic leukocytes in this study was discussed. 7. Proplasma cells, rarely plasma cells, appeared with a tendency to increase in number at later stage of starvation. 8. The most characteristic changes on circulating blood cells in complete starvation of rabbits were the leukoponia and failure of regeneration of erythroctes. These changes were considered as adaptive phenomena in response to the catabolic consumption of body constituents.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.287-295
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• 2022

Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ⁺/IL-4⁺ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V⁺/7-AAD⁺ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163⁺ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7965-7970
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• 2014

One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.

• Molecules and Cells
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• v.37 no.11
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• pp.804-811
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• 2014

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type $Ca^{2+}$ currents ($I_{Ca-N}$) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated $Ca^{2+}$ currents ($I_{Ca}$), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on $I_{Ca}$. This PAR-2-induced inhibition was almost completely prevented by ${\omega}$-CgTx, a potent N-type $Ca^{2+}$ channel blocker, suggesting the involvement of N-type $Ca^{2+}$ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited $I_{Ca-N}$ in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ${\omega}$-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type $Ca^{2+}$ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type $Ca^{2+}$ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.338-348
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• 1997

Background : Endotoxin, the component of outermembrane of gram negative organism, plays an important role in the initiation and amplification of inflammatory reaction by its effects on inflammatory cells. Until recently, there have been continuing efforts to delinate the mechanisms of the signal trasduction pathway of endotoxin stimuli on inflammatory cells. By uncovering the mechanisms of signal transduction pathway of endotoxin stimuli, we can expect to have tools to control the excessive inflammatory responses which sometimes may be fatal to the involved host. It was generally accepted that endotoxin exerts its inflammatory effects through inflammatory cytokines that are produced by endotoxin-stimulated inflammatory cells and there were some reports on the importance of protein kinase C and protein tyrosine kinase activation in the production of inflammatory cytokines by endotoxin So we evaluated the effect of pretreatment of protein kinase C inhibitors (H7, Staurosporin) and protein tyrosine kinase inhibitors(Herbimycin, Genistein) on the endotoxin-stimulated cytokines(IL-8 & TNF-$\alpha$) mRNA expression. Method : Peripheral blood monocytes were isolated from healthy volunteers by Ficoll-Hypaque density gradient method and purified by adhesion to 60mm Petri dishes. Endotoxin(LPS 100ng/ml) was added to each dishes except one control dish, and each endotoxin-stimulated dishes was preincubated with H7, Staurosporin(protein kinase C inhibitor), Herbimycin or Genistein(protein tyrosine kinase inhibitor) respectively except one dish. Four hours later the endotoxin stimulation, total RNA was extracted and Northern blot analysis for IL-8 mRNA and TNF-$\alpha$ mRNA was done. Result : Endotoxin stimulation increased the expression of IL-8 mRNA and TNF-$\alpha$ mRNA expression in human peripheral blood monocyte as expected and the stimulatory effect of endotoxin on TNF-$\alpha$ mRNA expression was inhibited by protein kinase C inhibitors(H7, Staurosporin) and protein tyrosine kinase inhibitors (Herbimycin, Genistein). The inhibitory effect of each drugs was increased with increasing concentration. The stimulatory effect of endotoxin on IL-8 mRNA was also inhibited by H7 and protein tyrosine kinase inhibitors (Herbimycin, Genistein) dose-dependently but not by Staurosporin. Conclusion : Protein kinase C and protein tyrosine kinase are involved in the endotoxin induced signal transduction pathway in human peripheral blood monocyte.

• BMB Reports
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• v.50 no.10
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• pp.504-509
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• 2017

Ischemia is a serious disease, characterized by an inadequate blood supply to an organ or part of the body. In the present study, we evaluated the effects of the anti-microbial peptide SR-0379 on the stem cell-mediated therapy of ischemic diseases. The migratory and tube-forming abilities of human endothelial progenitor cells (EPCs) were enhanced by treatment with SR-0379 in vitro. Intramuscular administration of SR-0379 into a murine ischemic hindlimb significantly enhanced blood perfusion, decreased tissue necrosis, and increased the number of blood vessels in the ischemic muscle. Moreover, co-administration of SR-0379 with EPCs stimulated blood perfusion in an ischemic hindlimb more than intramuscular injection with either SR-0379 or EPCs alone. This enhanced blood perfusion was accompanied by a significant increase in the number of CD31- and ${\alpha}$-SMA-positive blood vessels in ischemic hindlimb. These results suggest that SR-0379 is a potential drug candidate for potentiating EPC-mediated therapy of ischemic diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.163-168
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• 2014

Endothelial progenitor cells (EPCs) are known to play an important role in the repair of damaged blood vessels. We used an endothelial progenitor cell colony-forming assay (EPC-CFA) to determine whether EPC numbers could be increased in healthy individuals through regular exercise training. The number of functional EPCs obtained from human peripheral blood-derived AC133 stem cells was measured after a 28-day regular exercise training program. The number of total endothelial progenitor cell colony-forming units (EPC-CFU) was significantly increased compared to that in the control group (p=0.02, n=5). In addition, we observed a significant decrease in homocysteine levels followed by an increase in the number of EPC-CFUs (p=0.04, n=5), indicating that the 28-day regular exercise training could increase the number of EPC colonies and decrease homocysteine levels. Moreover, an inverse correlation was observed between small-endothelial progenitor cell colony-forming units (small-EPC-CFUs) and plasma homocysteine levels in healthy men (r=-0.8125, p=0.047). We found that regular exercise training could increase the number of EPC-CFUs and decrease homocysteine levels, thus decreasing the cardiovascular disease risk in men.

• Tuberculosis and Respiratory Diseases
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• v.81 no.2
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• pp.132-137
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• 2018

Background: The pathophysiology of chronic obstructive pulmonary disease (COPD) includes inflammation, oxidative stress, an imbalance of proteases and antiproteases and apoptosis which has been focused on lately. Abnormal apoptotic events have been demonstrated in both epithelial and endothelial cells, as well as in inflammatory cells including neutrophils and lymphocytes in the lungs of COPD patients. An increased propensity of activated T lymphocytes to undergo apoptosis has been observed in the peripheral blood of COPD patients. Therefore, the apoptosis of T lymphocytes without activating them was investigated in this study. Methods: Twelve control subjects, 21 stable COPD patients and 15 exacerbated COPD patients were recruited in the study. The T lymphocytes were isolated from the peripheral blood using magnetically activated cell sorting. Apoptosis of the T lymphocytes was assessed with flow cytometry using Annexin V and 7-aminoactinomycin D. Apoptosis of T lymphocytes at 24 hours after the cell culture was measured so that the T lymphocyte apoptosis among the control and the COPD patients could be compared. Results: Stable COPD patients had increased rates of $CD4^+$ T lymphocyte apoptosis at 24 hours after the cell culture, more than the $CD4^+$ T lymphocyte apoptosis which appeared in the control group, while the COPD patients with acute exacerbation had an amplified response of $CD4^+$ T lymphocyte apoptosis as well as of $CD8^+$ T lymphocyte apoptosis at 24 hours after the cell culture. Conclusion: Stable COPD patients have more apoptosis of $CD4^+$ T lymphocytes, which can be associated with the pathophysiology of COPD in stable conditions.

• Journal of Veterinary Clinics
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• v.22 no.2
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• pp.84-89
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• 2005

This study was undertaken to examine whether 1,2-benzopyrone affects on chemotactic activity of canine peripheral blood leukocytes. A modified Boyden chamber method was sed on chemotaxis evaluation. The direct treatments of 1,2-benzopyrone showed no ffects on the chemotaxis of peripheral blood mononuclear cells (PBMCs) and olymorphonuclear cells (PMNs). But chemotaxis of PMN was remarkably enhanced by ulture supernatant from PBMC but not PMN treated with 1,2-benzopyrone. Similarly, it as also increased by recombinant (r) interleukin (lL)­8. This chemotactic activity of MN was inhibited by addition of anti-rIL-8 polyclonal antibody. The chemotaxis of PBMC was not enhanced by culture supernatant from either PBMC or PMN treated with 1,2-benzopyrone. Therefore, these results suggested that the chemotactic activity of PMN ay be mainly mediated by IL-8-like factor(s) produced from PBMC treated with ,2-benzopyrone.

• Journal of Society of Preventive Korean Medicine
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• v.5 no.1
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• pp.103-115
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• 2001

Background : Gamisamryungbaekchul-san(加味蔘?白朮散) is a herbal medicine which has been used for the traditional therapeutic agent of augmentation of the spleen and reinforcement of the Qi. Objective : This Study was performed to investigate the effect of Gamisamryungbaekchul-san on the tumor and immune response in the moose B16 melanoma tumor model. Materials and Methods : The tumor was induced by subcutaneous inoculation of B16BL6 melanoma cells in the shaved dorsal region of mice. Mice were orally administered with Gamisamryungbaekchul-san extract(26.3mg/mouse) for 14days after inoculation. For making examination of antitumor effect, the Increase of life span, Tumor growth inhibition rate, change of body weight were measured and evaluated. For the immune response increasing effect, the percentage of T lymphocyte and B Lymphocyte in the peripheral blood, the percentage of CD4+ T-cell, CD8+ T-cell and CD4+/CD8+ ratio in the peripheral blood and spleen, interleukin-2 productivity were measured and evaluated. Results : Gamisamryungbaekchul-san showed 16.59% increase of life span, 31.64% tumor growth inhibition rate and increase of body weight. Gamisamryungbaekchul-san increased the percentage of T lymphocyte in the peripheral blood, CD4+ T cell percentage of peripheral blood and spleen, and Interleukin-2 productivity as compared with the Control group. Whereas Gamisamryungbaekchul-san had no effect on the percentage of B lymphocyte in the peripheral blood, the percentage of CD8+ T cell, CD4+/CD8+ T-cell ratio in both of peripheral blood and spleen as compared with the Control group. Conclusion : This study shows that Gamisamryungbaekchul-san has anti-tumor effects and immunoregulatory effects on the B16 melanoma tumor model. It is suggested that Gamisarmyungbaekchul-san could be a useful immunomodulator and anti-tumor agent.