• Journal of Ginseng Research
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• v.29 no.1
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• pp.1-18
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• 2005

Ginseng Radix, the root of Panax ginseng C. A. Meyer has been used in Eastern Asia for 2000 years as a tonic and restorative, promoting health and longevity. Two varieties are commercially available: white ginseng(Ginseng Radix Alba) is produced by air-drying the root, while red ginseng(Ginseng Radix Rubra) is produced by steaming the root followed by drying. These two varieties of different processing have somewhat differences by heat processing between them. During the heat processing for preparing red ginseng, it has been found to exhibit inactivation of catabolic enzymes, thereby preventing deterioration of ginseng quality and the increased antioxidant-like substances which inhibit lipid peroxide formation, and also good gastro-intestinal absorption by gelatinization of starch. Moreover, studies of changes in ginsenosides composition due to different processing of ginseng roots have been undertaken. The results obtained showed that red ginseng differ from white ginseng due to the lack of acidic malonyl-ginsenosides. The heating procedure in red ginseng was proved to degrade the thermally unstable malonyl-ginsenoside into corresponding netural ginsenosides. Also the steaming process of red ginseng causes degradation or transformation of neutral ginsenosides. Ginsenosides $Rh_2,\;Rh_4,\;Rs_3,\;Rs_4\;and\;Rg_5$, found only in red ginseng, have been known to be hydrolyzed products derived from original saponin by heat processing, responsible for inhibitory effects on the growth of cancer cells through the induction of apoptosis. 20(S)-ginsenoside $Rg_3$ was also formed in red ginseng and was shown to exhibit vasorelaxation properties, antimetastatic activities, and anti-platelet aggregation activity. Recently, steamed red ginseng at high temperature was shown to provide enhance the yield of ginsenosides $Rg_3\;and\;Rg_5$ characteristic of red ginseng Additionally, one of non-saponin constituents, panaxytriol, was found to be structually transformed from polyacetylenic alcohol(panaxydol) showing cytotoxicity during the preparation of red ginseng and also maltol, antioxidant maillard product, from maltose and arginyl-fructosyl-glucose, amino acid derivative, from arginine and maltose. In regard to the in vitro and in vivo comparative biological activities, red ginseng was reported to show more potent activities on the antioxidant effect, anticarcinogenic effect and ameliorative effect on blood circulation than those of white ginseng. In oriental medicine, the ability of red ginseng to supplement the vacancy(허) was known to be relatively stronger than that of white ginseng, but very few are known on its comparative clinical studies. Further investigation on the preclinical and clinical experiments are needed to show the differences of indications and efficacies between red and white ginsengs on the basis of oriental medicines.

• The Korean Journal of Zoology
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• v.13 no.3
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• pp.68-74
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• 1970

In the previous studies, the present author found that high proportion of the follicular oocytes from mouse and rabbit ovaries are able to resume their maturation division in the anterior chamber of the eye in which they have been incubated by auto- or homoplastic transplantation. Especially in the case of the homoplastic transplantation, it was known that no trouble has been detected in the process of resumption of the oval maturation in particular connection with the antigen-antibody reaction between donor and recipient. These findings provide a possibility that the follicular oocytes from various animals would be matured in the eye even after the xenoplastic transplantation. Under such an assumption, the present studies were performed to examine the behavior of the follicular oocytes in the eye chamber of the animals of different species. For the donor of the follicular oocytes, domestic rabbits, albino rats of Sprague-Dowley strain, and albino mice of A-strain bred in our laboratory were used. The oocytes obtained from the ovarian follicules were introduced to the anterior chamber of the eye of different species of animals, with an exception of rabbit in which only the female animals were used as a recipient. The procedures of collection of ova, introduction to the eye, harvest from the eye ball, fixation, and staining were the same as mentioned in the previous reports (Cho, 1967b; Cho and Kim, 1968). The conclusions obtained are summarized as below. 1. The rabbit follicular oocytes are able to mature in the eye chambers of both male mouse and rat, although the proportion of the maturation is lower than when they are incubated autoplastically in the eye. When the ova were incubated in the male mouse eye for 24 hours, 21 per cent of them showed chromosomes at metaphase I and II, whereas the rate was 32 per cent when they were incubated in the eye of the male rat. These are apparently low comparing to the rate of 52 per cent of autoplastic transplantation. 2. When rat follicular oocytes were transferred into the mouse eye chamber and recovered after 24 hours, 43 per cent of them produced the mataphase I and II chromosomes. This proportion was higher than the result of the homoplastic transplantation which yielded 23 per cent of the ova on maturation. 3. The most striking result was found in the experiment with mouse follicular oocytes. Seventy-six per cent of the oocytes resumed their maturation division within 24 hours after they were transferred into the male rat eye chamber, and this figure was significantly high compared to the result o 55 per cent obtained by the homoplastic transplantation. In the rat eye, the induction of the degenerative ova also was low (19%). On the other hand, the proportion of the oval maturation decreased to 45 per cent, while that of degeneration increased 33 per cent when they were incubated in the eye of the female rabbit. 4. It was apparent from the present experiments that the follicular oocytes can reveal their activation to maturation in the eye chamber which contains aqueous humor which is known to be composed of low protein content and of very little gamma-globulin which acts as an antibody(Oser, 1965), and that it shows higher osmolarity than blood serum(Levene, 1958). Taking these properities into consideration the humor may provide unfavourable environment to the cells and tissues incubated in. However, it could be noteworthy finding that only the follicular oocytes in the eye of the different species can grow in healthy condition although the maturation rates are varied with the animal species. The fact that the rabbit follicular oocytes show the lower proportion in maturation may be due to the greater amount of the yolk granules in the egg cytoplasm than those in the mouse and rat oocytes. That the mouse oocytes incubated in the eye of the rat mouse and rat oocytes. That the mouse oocytes incubated in the eye of the rat resumed their maturation process in greater proportion would e explained by the fact that the rat eye chamber particularly provides the better environment to the mouse oocytes than the eye chamber of mouse does.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.516-524
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• 1998

Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were $92.4{\pm}5.9%$ and $84.7{\pm}4.6%$, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and $6.59{\times}10^9\;M^{-1}$, respectively, while those of Re-188-CEA79.4 were 41.6% and $4.2{\times}10^9\;M^{-1}$, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.545-558
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• 2003

Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

• Tuberculosis and Respiratory Diseases
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• v.55 no.5
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• pp.449-458
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• 2003

Background : The poor prognostic factors of far-advanced pulmonary tuberculosis(FAPTB) are lymphocytopenia in the peripheral blood(PB)(< $1,000/mm^3$) and $T_4$-cell count ${\leq}500/mm^3$. However, the cause of PB lymphocytopenia in FAPTB is unclear. The aim of this study was to analyze the lymphocyte proportion and cytokines of the bone marrow(BM) in FAPTB patients with peripheral lymphocytopenia in order to clarify whether the limiting step of the lymphocytopenia occurs in production, differentiation, or circulation. Methods : This study included patients with FAPTB between August 1999 and August 2002 who visited Gachon Medical School Gil Medical Center. The exclusion criteria were old age(${\geq}65years$), cachexia or a low body weight, shock, hematologic diseases, or BM involvement of tuberculosis. The distributions of cells in PB and BM were analyzed and compared to the control group. The interleukin(IL)-2, IL-7, IL-10, TNF-${\alpha}$, Interferon-${\gamma}$, and TGF-${\beta}$ levels in the BM were measured by ELISA. Result : Thirteen patients(male : female=9:4) were included and the mean age was $42{\pm}12$years. The proportion and count of the lymphocytes in the PB were significantly lower in the FAPTB group ($7.4{\pm}3.0%$, $694{\pm}255/mm^3$ vs. $17.5{\pm}5.8%$, $1,377{\pm}436/mm^3$, each p=0.0001 and 0.002). The proportion of immature lymphocyte in the BM showed a decreasing trend in the FAPTB group($9{\pm}4%$ vs. $12{\pm}3%$, p=0.138). The IL-2($26.0{\pm}29.1$ vs. $112.2{\pm}42.4pg/mL$, p=0.001) and IL-10($3.4{\pm}4.7$ vs. $12.0{\pm}8.0pg/mL$, p=0.031) levels in the BM were significantly lower in the FAPTB group than those in control. The levels of the other cytokines in FAPTB group and control were similar. Conclusion : These results suggest that the cause of lymphocytopenia in PB is associated with a abnormality IL-2 and IL-10 production in the BM. More study will be needed to define the mechanism of a decreased reservoir in BM.

• Journal of Gastric Cancer
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• v.5 no.1
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• pp.10-15
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• 2005

Purpose: Recently the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, immature vascular disease, neural tube defect, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancer, and particularly gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metaboism, and influences DNA synthesis and DNA methylation. Generally, folate deficiency is associated with gastrointestinal neoplasms. The amino-acid- changing and enzyme-activity-reducing nucleotide polymorphism (766C$\rightarrow$T/ Ala222Val) has been described in the MTHFR polymorphism and leads to low enzyme activity that may reduce the capacity of DNA methylation and possibly uracil mis-incorporation into DNA. These processes may be critical in the oncogenic transformation of human cells, especially in colorectal carcinomas. We investigated the relationship between the MTHFR polymorphism in gastric cancer and the tumor site, the smoking history, and the alcoholic history. Materials and Methods: Ninety-six (96) individuals with gastric cancer and 287 healthy persons were analyzed. Blood sampling was performed, PCR-RFLP was analyzed, and MTHFR polymorphism genotypes of C/C, C/T, and T/T were obtained and analyzed statistically for their correlation. Results: In the gastric cancer group there were 69 ($72\%$) males and 27 ($28\%$) females. There were also 58 cases ($60\%$) involving the gastric lower body, 20 cases ($21\%$) the gastric mid-body, and 18 cases ($19\%$) the gastric upper body. In the control group there were 169 ($59\%$) males and 118 ($41\%$) females. Among the gastric cancer, 56 ($61\%$) smoking patients, 40 ($39\%$) non-smoking patients, 45($47\%$) alcoholic patients, 51 ($53\%$) non-alcoholic patients. In the gastric cancer group, MTHER polymorphisms were C/C in 18 ($19\%$) cases, C/T in 59 ($61\%$) cases, T/T in 19 ($20\%$) cases. In the control group polymorphisms were C/C 116 ($40\%$) cases, C/T 103 ($36\%$) cases, and T/T 68 ($24\%$) cases (P=0.045). In cases of lower gastric body cancer, polymorphisms were C/C in 16 ($24\%$) C/C in 16 ($24\%$) cases and C/T or T/T in 42 ($72\%$) cases. In cases of upper and mid-body cancer, polymorphisms were C/C in 2 ($5\%$) cases and C/T or T/T 36 ($95\%$) cases (P=0.006). In the non-smoking patient group, polymorphisms were C/C in 5 (12%) cases and C/T or T/T in 35 ($88\%$) cases. In the smoking patient group, C/C in 13 ($23\%$) cases and C/T or T/T in 43 ($77\%$) cases (P=0.189). In the non-alcoholic patient group, polymorphisms were C/C in 6 ($12\%$) cases and C/T or T/T in 45 ($88\%$) cases. In the alcoholic patient group, polymorphisms were C/C in 12 ($26\%$) cases and C/T or T/T in 33 ($74\%$) cases (P=0.063) Conclusion: MTHFR polymorphisms are associated with gastric cancer and tumor site, but not with smoking and alcohol drinking.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1343-1352
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• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.307-313
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• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Clinical and Experimental Reproductive Medicine
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• v.23 no.3
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• pp.247-268
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• 1996

It has been known for a long time that gonadotropins and steroid hormones play a pivotal role in a series of reproductive biological phenomena including the maturation of ovarian follicles and oocytes, ovulation and implantation, maintenance of pregnancy and fetal growth & development, parturition and mammary development and lactation. Recent investigations, however, have elucidated that in addition to these classic hormones, multiple growth factors also are involved in these phenomena. Most growth factors in reproductive organs mediate the actions of gonadotropins and steroid hormones or synergize with them in an autocrine/paracrine manner. The insulin-like growth factor(IGF) system, which is one of the most actively investigated areas lately in the reproductive organs, has been found to have important roles in a wide gamut of reproductive phenomena. In the present communication, published literature pertaining to the intrauterine IGF system will be reviewed preceded by general information of the IGF system. The IGF family comprises of IGF-I & IGF-II ligands, two types of IGF receptors and six classes of IGF-binding proteins(IGFBPs) that are known to date. IGF-I and IGF-II peptides, which are structurally homologous to proinsulin, possess the insulin-like activity including the stimulatory effect of glucose and amino acid transport. Besides, IGFs as mitogens stimulate cell division, and also play a role in cellular differentiation and functions in a variety of cell lines. IGFs are expressed mainly in the liver and messenchymal cells, and act on almost all types of tissues in an autocrine/paracrine as well as endocrine mode. There are two types of IGF receptors. Type I IGF receptors, which are tyrosine kinase receptors having high-affinity for IGF-I and IGF-II, mediate almost all the IGF actions that are described above. Type II IGF receptors or IGF-II/mannose-6-phosphate receptors have two distinct binding sites; the IGF-II binding site exhibits a high affinity only for IGF-II. The principal role of the type II IGF receptor is to destroy IGF-II by targeting the ligand to the lysosome. IGFs in biological fluids are mostly bound to IGFBP. IGFBPs, in general, are IGF storage/carrier proteins or modulators of IGF actions; however, as for distinct roles for individual IGFBPs, only limited information is available. IGFBPs inhibit IGF actions under most in vitro situations, seemingly because affinities of IGFBPs for IGFs are greater than those of IGF receptors. How IGF is released from IGFBP to reach IGF receptors is not known; however, various IGFBP protease activities that are present in blood and interstitial fluids are believed to play an important role in the process of IGF release from the IGFBP. According to latest reports, there is evidence that under certain in vitro circumstances, IGFBP-1, -3, -5 have their own biological activities independent of the IGF. This may add another dimension of complexity of the already complicated IGF system. Messenger ribonucleic acids and proteins of the IGF family members are expressed in the uterine tissue and conceptus of the primates, rodents and farm animals to play important roles in growth and development of the uterus and fetus. Expression of the uterine IGF system is regulated by gonadal hormones and local regulatory substances with temporal and spatial specificities. Locally expressed IGFs and IGFBPs act on the uterine tissue in an autocrine/paracrine manner, or are secreted into the uterine lumen to participate in conceptus growth and development. Conceptus also expresses the IGF system beginning from the peri-implantation period. When an IGF family member is expressed in the conceptus, however, is determined by the presence or absence of maternally inherited mRNAs, genetic programming of the conceptus itself and an interaction with the maternal tissue. The site of IGF action also follows temporal (physiological status) and spatial specificities. These facts that expression of the IGF system is temporally and spatially regulated support indirectly a hypothesis that IGFs play a role in conceptus growth and development. Uterine and conceptus-derived IGFs stimulate cell division and differentiation, glucose and amino acid transport, general protein synthesis and the biosynthesis of mammotropic hormones including placental lactogen and prolactin, and also play a role in steroidogenesis. The suggested role for IGFs in conceptus growth and development has been proven by the result of IGF-I, IGF-II or IGF receptor gene disruption(targeting) of murine embryos by the homologous recombination technique. Mice carrying a null mutation for IGF-I and/or IGF-II or type I IGF receptor undergo delayed prenatal and postnatal growth and development with 30-60% normal weights at birth. Moreover, mice lacking the type I IGF receptor or IGF-I plus IGF-II die soon after birth. Intrauterine IGFBPs generally are believed to sequester IGF ligands within the uterus or to play a role of negative regulators of IGF actions by inhibiting IGF binding to cognate receptors. However, when it is taken into account that IGFBP-1 is expressed and secreted in primate uteri in amounts assessedly far exceeding those of local IGFs and that IGFBP-1 is one of the major secretory proteins of the primate decidua, the possibility that this IGFBP may have its own biological activity independent of IGF cannot be excluded. Evidently, elucidating the exact role of each IGFBP is an essential step into understanding the whole IGF system. As such, further research in this area is awaited with a lot of anticipation and attention.