• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.6
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• pp.805-813
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• 2005

In our previous study, a novel herb mixture (HIM-I) of Angelim gigas radix, Cnidium officinale rhizoma, and Paeonia japonica radix was developed to protect the intestinal and immune systems and promote its recovery against radiation damage. In this study, a new herbal preparation (HemoHIM) with the high immune modulating activity was developed from HIM-I. HIM-I was fractionated into ethanol fraction (HIM-I-E) and polysaccharide fraction (HIM-I-P). And HemoHIM was prepared by adding HIM-I-P to HIM-I. The protective activities against $\gamma$ -irradiation were compared among HemoHIM, HIM-I and the fractions. HemoHIM and HIM-I significantly decreased the radiation-induced DNA damage in vitro, and scavenged hydroxyl radicals in a dose-dependent manner. HemoHIM showed similar activity to HIM-I. In vitro proliferation assay with mouse lymphocytes and bone marrow cells showed that HIM-I-P was remarkably higher than HIM-I and HIM-I-E in cell proliferating activity. HemoHIM showed higher activity than HIM-I and this might be associated with the higher polysaccharide content. The in vivo protective effects of HemoHIM and HIM-I were investigated in $\gamma$-irradiated mice. HemoHIM increased the surviving intestinal crypts to a similar extent compared with HIM-I. In contrast, HemoHIM appeared to be more effective than HIM-I in endogenous spleen colony formation assay. The recovery of white blood cells and lymphocytes in irradiated mice were significantly enhanced by the administration of HemoHIM. Also HemoHIM administration prolonged the survival of irradiated mice. These results showed that the novel herbal preparation, HemoHIM, effectively protected the self-renewal tissues and immune system, and promoted the survival of irradiated mice. Moreover, in comparison with HIM-I, HemoHIM maintained similar activity in the reduction of oxidative damage of self-renewal tissue but exhibited the higher activity in protection and proliferation of immune and hematopoietic cells. These results suggested that HemoHIM might be more effective than HIM-I in immune modulation as well as radioprotection.

• Applied Biological Chemistry
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• v.18 no.2
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• pp.71-97
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• 1975

To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

• Journal of Plant Biotechnology
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• v.33 no.3
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• pp.195-207
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• 2006

Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

• Applied Microscopy
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• v.40 no.2
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• pp.73-80
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• 2010

Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.5
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• pp.605-612
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• 2005

In previous studies, we evaluated the effect of the 6 energy-tonic or blood-building prescriptions of traditional oriental medicine, and observed that Si-Wu-Tang and Bu-Zhong-Yi-Qi-Tang showed high activity in the protection of the gastrointestinal and hematopoietic organs in irradiated mice. But any of these prescriptions did not show a high activity in the activation of the immune cells. We performed this study to design an herb mixture which protects the self-renewal tissues and also promotes recovery of the immune system against radiation damage. In order to meet all the requirements, we designed a new mixture of 3 edible herbs listed in Korean Food Code. The mixture of Angelim gigas radix, Cnidium officinale rhizoma and Paeonia japonica radix was decocted with hot water, and the activities of the water extract (HIM-I) were evaluated. HIM-1 stimulated the immune cells in a much higher extent than the traditional prescriptions, and promoted dramatically the growth of bone marrow stem cells in vitro. Also, HIM-1 protected digestive and hematopoietic organs against radiation as effectively as the 2 prescriptions, Si-Wu-Tang and Bu-Zhong-Yi-Qi-Tang. On the other hand, it showed high in vitro antioxidative activity that might be considered as a mechanism of the protective effects against radiation. Although the detailed mechanisms of those effects remain to be elucidated, these results indicated that HIM-I might be a useful agent for protection and recovery of body from various risk factor as well as radiation, especially since it is a relatively nontoxic natural product.

• Laboratory Medicine Online
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• v.1 no.1
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• pp.57-63
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• 2011

Background: ABO antibody titration is useful for the evaluation of ABO-incompatible bone marrow or solid organ transplantations, yet the results quite vary between different test methods used. We compared the results of microcolumn agglutination and tube methods. Methods: Anti-A and anti-B isoagglutionin titers were determined in 63 healthy individuals (23 O, 20 A, and 20 B blood groups) using 4 different methods: immediate spin tube (tube), microcolumn agglutination without anti-human globulin (AHG) (CAT), tube with AHG (tube-AHG) and microcolumn agglutination with AHG (CAT-AHG). Results: The median (range) titers of anti-A and anti-B in group O individuals by tube, CAT, tube-AHG, and CAT-AHG methods were 64 (8-512), 64 (8-512), 128 (8-2,048), and 128 (16-2,048); 64 (16-128), 128 (16-256), 128 (16-512), and 256 (16-512), respectively. The median (range) titers of anti-A in group B and anti-B in group A individuals by the four methods were 64 (16-128), 128 (8-128), 128 (8-256), and 256 (8-256); 64 (8-128), 64 (8-128), 32 (8-128), and 64 (8-256), respectively. The isoagglutinin titer measured by CAT-AHGmethod was the highest. The titers measured by CAT and CAT-AHG methods were 0-1 titer higher than those by tube and tube-AHG methods, respectively. Whatever method was used, the isoagglutinin titers were higher in women than in men. Conclusions: CAT-AHG was the most sensitive method among the four methods tested. Since AHG titer values are critical for the clinical management and CAT has less manual procedures than tube method, CAT-AHG method could be used for the standardization of ABO antibody titration in different institutions.

• Journal of Preventive Medicine and Public Health
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• v.27 no.1 s.45
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• pp.11-24
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• 1994

The studies reported here were undertaken to investigate the effects of mercury chloride on immune system of Balb/c mouse employing a flexible tier of in vitro and in vivo assays. Mercury chloride inhibited the proliferative responses of spleen cells to lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin as a dose-dependent manner. This inhibitory effect was observed not only when $HgCl_2$ was added 2nd or 3rd day of 3 days culture period but also when spleen cells was pretreated with $HgCl_2$ for 2 hours. Mercury chloride, however, potentiated the production of IgM and IgG from spleen cells. During the $HgCl_2$ administration by drinking for 3 weeks, the weight gain of mice was significantly blunted than that o control group mice, while no overt signs related to mercury toxicity were noted in any mice of experimental group. There was no change in thymus and spleen weights, and in histological findings of kidney, bone marrow of femur, thymus, spleen, and popliteal lymph node after 3 weeks of mercury exposure. However, $HgCl_2$ induced a significant increase of total serum IgM, IgG including $IgG_1,\;IgG_{2a}\;and\;IgG_{2b}$, and IgE in Balb/c mice. Treatment in vivo with anti-IL-4 monoclonal antibody significantly abrogated the $HgCl_2$-induced increase in total serum IgG1 and IgE. Whereas $HgCl_2$ potentiated total serum IgM and IgG, there was no difference in total serum hemagglutinin to SRBC (Sheep Red Blood Cell) between experimental and control group mice when these mice were immunized with SRBC. All these findings observed in Balb/c mice suggest that mercury perturbates well-orchestrated regulation of immune responses before developing histopathological changes in lymphoid tissues.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.3
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• pp.169-175
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• 2016

Saccharin (o-benzoic sulfimide) is the first artificial and non-caloric sweetener that was first synthesized in 1879. In this study, we examined the biological activity of saccharin against various human cancer cell lines and human bone marrow-derived mesenchymal stem cells. A viability assay based on the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was performed to test for the cytotoxicity of saccharin about the four human cancer cell lines (H460, H157, A549 and SKOV3), one murine cancer cellline (Raw264.7), and MSCs. In order to find the differentially expressed gene in saccharin-treated MSCs against untreated MSCs, we performed annealing control primer (ACP)-based differential display reverse transcriptionp-olymerase chain reaction (DDRT-PCR). All tested cells were treated with saccharin at various concentrations (0.0, 4.8, 7.2, 9.6, 12.0, 14.4 mg/mL) for 48 hr. The number of metabolically active cancer cells decreased when treated with the saccharin at various concentrations for 48 hr as compared with the untreated cells. The decrease in cell survival was more evident with increasing concentrations of saccharin. Moreover, novel candidate genes, which were differentially expressed in MSCs in response to saccharin, were identified in 16 bands on 2% agarose gel. This revealed 16-7 up-regulated and 9 down-regulated-differentially expressed genes indicated by arrows. One of these candidate genes was a FK506-binding protein gene. The functional roles of FK506 binding proteins, with respect to the activities of stem cell proliferation, were not characterized. Further studies are required to get a better understanding of FK506-binding proteins in its roles in increasing stem cell proliferative activities from using saccharin.

• Journal of Yeungnam Medical Science
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• v.14 no.2
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• pp.359-369
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• 1997

We studied the expression of the cell surface antigen associated with myeloid and lymphoid leukemias on bone marrow or peripheral blood blast cells from 153 leukemic patients including 61 cases of acute myelogenous leukemias(AML), 46 of acute lymphocytic leukemias(ALL) and 12 of acute leukemias. They were analyzed by direct or indirect immunofluorescence method for reactivity with the monoclonal antibodies to B cells(CD10, CD19, SmIg), T cells(CD2, CD5, CD7, CD3, CD4, CD8), myeloid antigen(CD13, CD14, CD33, CD61) and a nonspecific antigen, HLA-DR. Lymphoid associated markers detected on AML is CD7 32.8%, CD10 14.8%, CD5 13.1%, CD2 6.6% and CD19 1.6%. TdT was positive in 4.9% of AMLs. Hybrid leukemias were 8 cases out 61 AML cases and were mainly composed of monocytic lineage, M4 and M5a. Myeloid markers detected in ALL were CD13 2.2% and CD33 2.2%. In this study, immunologically classified ALLs were composed of 65.2% of CALLA (+) B precursor type, 10.9% of CALLA (-) B precursor pattern, 8.7% of T cell type, 2.2% of B cell type, 4.5% of mixed lymphoid lineage(B&T), 2.2% of undifferentiated leukemia, and 6.5% of hybrid leukemia. Twelve cases of acute leukemias ware finally diagnosed to be 5 cases of hybrid leukemia, 3 cases of B lineage, 3 case of T lineage and 1 case of mixed lymphoid(B&T) leukemia. In summary, we think the best method for typing acute leukemias is by using a combination of FAB classification and immunophenotying.

• Childhood Kidney Diseases
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• v.11 no.2
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• pp.247-254
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• 2007

Purpose : Continuous renal replacement therapy(CRRT) has been the first choice for the treatment of acute renal failure in critically ill children not only in western countries but also in Korea. However, there are very few studies that have analyzed the outcome and prognosis of this modality in Korean children. We performed this study to evaluate the factors associated with the outcome and prognosis of patients treated with CRRT. Methods : We retrospectively reviewed the medical records of 32 children who had received CRRT at Severance hospital from 2003 to 2006. The mean age was 7.5 years(range 4 days-16 years) and the mean body weight was 25.8 kg (range 3.2-63 kg). Results : Eleven(34.4%) of the 32 patients survived. Bone marrow transplantation and malignancy were the most common causes of death and underlying disease leading to the need for CRRT Mean patient weight, age, duration of CRRT, number of organ failures, urine output, estimated glomerular filtration rate(eGFR), C-reactive protein, and blood urea level did not differ significantly between survivors and nonsurvivors. (1) Pediatric risk of mortality(PRISM) III score at CRRT initiation($9.8{\pm}5.3$ vs. $26.7{\pm}7.6$, P<0.0001), (2) maximum pressor number ($2.1{\pm}1.2$ vs. $3.0{\pm}1.0$, P=0.038), and (3) the degree of fluid overload($5.2{\pm}6.0$ vs. $15.0{\pm}8.9$, P=0.002) were significantly lower in survivers than in nonsurvivors. Multivariate analysis revealed that fluid overload was the only independent factor reducing survival rate. Conclusion : CRRT was successfully applied to the treatment of acute renal failure in a wide range of critically ill children. To improve survival, we suggest the early initiation of CRRT to prevent the systemic worsening and progression of fluid overload in critically ill children with acute renal failure. (J Korean Soc Pediatr Nephrol 2007;11:247-254)