• Journal of Life Science
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• v.22 no.1
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• pp.41-48
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• 2012

Bee venom (BV) has been used in medicine to treat a variety of diseases including arthritis, rheumatism, and various cancers. Recent reports indicate that BV has anti-angiogenic effects, but the precise molecular mechanism underlying the effects of BV against colorectal cancer remains to be elucidated. We examined the effects of BV and its major components (melittin and apamin) on tumor angiogenesis and found that BV significantly decreased protein levels of hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), an important factor involved in angiogenesis and tumor progression, in human colorectal carcinoma HCT116 cells. BV also suppressed the transcription of HIF-$1{\alpha}$ under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major target gene of HIF-$1{\alpha}$. We also found that these effects were mainly elicited by apamin, but not melittin. BV specifically inhibited the phosphorylation of ERK1/2 without changing the total levels of this protein, but had no effect on kinases of p38/JNK and AKT. Our results suggest that BV may inhibit human colorectal cancer progression and angiogenesis by inhibiting HIF-$1{\alpha}$ and VEGF expression, thereby providing a novel potential mechanism for the anticancer action of BV.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.40 no.6
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• pp.684-696
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• 1995

A mutant for chalky endosperm and genetic male sterility (GMS) was newly developed in rice. The two characters were found to be controlled by single recessive gene which has pleiotropic effect, indicating that chalky seeds should be GMS seeds in segregating populations. Chalky seeds showed the same shape and size as normal seeds. However, starch composition of central part of endosperm was looser and shape of starch granules was rounder compared with normal endosperm, resulting in significantly lower grain weight, absolute density and grain hardness in chalky grains than in normal ones. Amylose content and gel consistency of chalky grains were much lower and harder, respectively. Male sterile plants showed much shorter plant height, poorer panicle exsertion and lesser panicle number compared with normal plants. Microspore abortion stage in pollen developmental process was observed as before meiosis. Male sterility of the mutant was stable regadless of temperature and day length. A system breeding hybrid rice using this mutant was discussed, comp ring with other systems utilizing cytoplasmic-genic male sterility(CGMS) and environment sensitive GMS(EGMS). Separation of GMS seeds in mixed seed bulks by specific gravity (1.14∼1.16g / cm3) was successful about 85∼90%. But some mixed normal plants were seemed to be easily removed by the apparent difference in growth characters at seedling stage. The highest natural outcrossing rate of this GMS line was as 17.3 % in a plot treated with 2-row pollinator, I-row GMS, and GA3 + cutting of flag leaf + pollen-scattering by rope.

• Development and Reproduction
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• v.5 no.2
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• pp.175-180
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• 2001

The ectopic expression of gonadotropin releasing hormone(GnRH and luteinizing hormone(LH) in several tissues is a quite intriguing phenomenon. Recently, the presence of GnRH and its receptor has been clearly demonstrated in rodents and human mammary gland. In this context, one can postulate that the presence of local circuit composed of GnRH and LH in the gland. The present study was undertaken to elucidate whether there is a correlation between the LH expression in rat mammary gland and physiological status during the process of mammary differentiation. LH contents in mammary gland from cycling to weaning rats were measured by radioimmunoassay(RIA). In cycling rats, changes of the LH level in both serum and mammary gland showed similar pattern as the highest level in proestrus and the lowest level in diestrus II stage. While the serum LH levels were fluctuated from pregnant through involution stage, a sharp decline of mammary LH contents was observed in the lactating rats. This decrement was recovered in involuting rats to the level of proestrus stage. Reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analyses demonstrated that the transcriptional activities of the mammary LH and GnRH were increased from diestrus I stage to estrus stage, and the increased levels were maintained in pregnant, lactation and involution stages. To test the hypothesis that the alteration in mammary LH expression might be steroid-dependant, ovariectomy(OVX) and steroid supplement model was employed. As expected, supplement of estradiol(E$_2$) after OVX remarkably decreased serum LH level compared to that in serum from vehicle-only treated rats. Likewise, administration of E$_2$ significantly reduced the mammary LH content. The present study demonstrated that (i) the LH expression in mammary gland could be altered by some physiological parameters such as estrous cycle, pregnancy, lactation and involution, and (ii) ovarian steroid especially estrogen seems to be one of major endocrine factors which are responsible for regulation of mammary LH expression.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.34-41
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• 2016

Adult-onset type II citrullinemia (CTLN2) is characterized by episodes of neurologic symptoms associated with hyperammonemia leading to disorientation, irritability, seizures, and coma. CTLN2 is distinct from classical citrullinemia, which is caused by a mutation of the argininosuccinic acid synthetase (ASS) gene. The serum citrulline level is elevated, while the activity of ASS in liver tissue is decreased. CTLN2 is known to have a poor prognosis if the proper treatment is not taken. We reported a female aged 37 years who developed recurrent attacks of altered consciousness, aberrant behavior, and vomiting. We initially suspected the patient had CTLN2 because of the signs of hyperammonemic encephalopathy, such as altered mentality, memory disturbance, and aberrant behaviors provoked by exercise-induced stress and excessive intravenous amino acid administration. Through her peculiar diet preferences and laboratory findings that included hyperammonemia and citrullinemia, we diagnosed the patient as CTLN2, and SLC25A13 sequencing revealed known compound heterozygous mutations (IVS11+1G>A, c.674C> A). Her parents were heterozygous carriers, and we identified that her older sister had the same mutations. The older sister had not experienced any episodes of hyperammonemia, but she had peculiar diet preferences. The patient and her sister have been well with conservative management. When considering the clinical course of CTLN2, it was meaningful that the older sister could be diagnosed early in an asymptomatic period and that preemptive treatment was employed. Through this case, CTLN2 should be considered in adults who present symptoms of hyperammonemic encephalopathy without a definite etiology. Because of its rare incidence and similar clinical features, CTLN2 is frequently misdiagnosed as hepatic encephalopathy, and it shows a poor prognosis due to the lack of early diagnosis and proper treatment. A high-carbohydrate diet, which is usually used to treat other urea cycle defects, can also exaggerate the clinical course of CTLN2, so proper metabolic screening tests and genetic studies should be performed.

• Applied Microscopy
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• v.34 no.3
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• pp.171-178
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• 2004

Metallothionein (MT) is a family of ubiquitous, low molecular weight (6-7 kDa), cysteine-rich protein with a high affinity to metal ions and has no aromatic amino acids and histidine. Some of the known functions of MT include detoxification of heavy metals and alkylating agents and neutralization of free radicals. Also, this protein may affect a number of cellular processes including gene expression, apoptosis, proliferation and differentiation. But, its actual functions are still not clear. The present study was undertaken to examine immunocytochemically the localization of MT in developing rat liver. On the day 11 of gestation, the fetal rat liver has already been formed and contained numerous oval cells with high nuclear cytoplasmic ratio, which were the progenitors of hepatic parenchymal cells, but no reaction products of MT were detected at this time. And then, positive reactions against MT started to appear predominantly in the parenchymal cells of liver from the 13th day after gestation. Reaction products, immunogold particles or brown coloration, were localized at both the nucleus and the cytoplasm of the parenchymal cells, except mitochondria. The intensity of this reaction gradually increased, and exhibited the strongest at birth. The intensity of MT staining and immunogold labelling diminished with growth, and by the 15th day after birth weak positive reaction was observed in the cells. In brief, positive reactions for MT were observed in the oval cells and the parenchymal cells during fetal stage, meanwhile they were present only in the parenchymal cells after birth. The present results suggest that MT possibly involves parechymal cell proliferation and differentiation through the storage or the supply of various metal ions in the developing rat liver.

• Natural Product Sciences
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• v.8 no.1
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• pp.1-15
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• 2002

An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

• Korean Journal of Plant Tissue Culture
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• v.27 no.6
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• pp.423-428
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• 2000

In 1997 when cloned sheep Dolly and soon after Polly were born, it had become head-line news because in the former the nucleus that gave rise to the lamb came from cells of six-year-old adult sheep and in the latter case a foreign gene was inserted into the donor nucleus to make the cloned sheep produce human protein, factor IX, in e milk. In the last few years, once the realm of science fiction, cloned mammals especially in livestock have become almost commonplace. What the press accounts often fail to convey, however, is that behind every success lie hundreds of failures. Many of the nuclear-transferred egg cells fail to undergo normal cell divisions. Even when an embryo does successfully implant in the womb, pregnancy often ends in miscarriage. A significant fraction of the animals that are born die shortly after birth and some of those that survived have serious developmental abnormalities. Efficiency remains at less than one % out of some hundred attempts to clone an animal. These facts show that something is fundamentally wrong and enormous hurdles must be overcome before cloning becomes practical. Cloning researchers now tent to put aside their effort to create live animals in order to probe the fundamental questions on cell biology including stem cells, the questions of whether the hereditary material in the nucleus of each cell remains intact throughout development, and how transferred nucleus is reprogrammed exactly like the zygotic nucleus. Stem cells are defined as those cells which can divide to produce a daughter cell like themselves (self-renewal) as well as a daughter cell that will give rise to specific differentiated cells (cell-differentiation). Multicellular organisms are formed from a single totipotent stem cell commonly called fertilized egg or zygote. As this cell and its progeny undergo cell divisions the potency of the stem cells in each tissue and organ become gradually restricted in the order of totipotent, pluripotent, and multipotent. The differentiation potential of multipotent stem cells in each tissue has been thought to be limited to cell lineages present in the organ from which they were derived. Recent studies, however, revealed that multipotent stem cells derived from adult tissues have much wider differentiation potential than was previously thought. These cells can differentiate into developmentally unrelated cell types, such as nerve stem cell into blood cells or muscle stem cell into brain cells. Neural stem cells isolated from the adult forebrain were recently shown to be capable of repopulating the hematopoietic system and produce blood cells in irradiated condition. In plants although the term$\boxDr$ stem cell$\boxUl$is not used, some cells in the second layer of tunica at the apical meristem of shoot, some nucellar cells surrounding the embryo sac, and initial cells of adventive buds are considered to be equivalent to the totipotent stem cells of mammals. The telomere ends of linear eukaryotic chromosomes cannot be replicated because the RNA primer at the end of a completed lagging strand cannot be replaced with DNA, causing 5' end gap. A chromosome would be shortened by the length of RNA primer with every cycle of DNA replication and cell division. Essential genes located near the ends of chromosomes would inevitably be deleted by end-shortening, thereby killing the descendants of the original cells. Telomeric DNA has an unusual sequence consisting of up to 1,000 or more tandem repeat of a simple sequence. For example, chromosome of mammal including human has the repeating telomeric sequence of TTAGGG and that of higher plant is TTTAGGG. This non-genic tandem repeat prevents the death of cell despite the continued shortening of chromosome length. In contrast with the somatic cells germ line cells have the mechanism to fill-up the 5' end gap of telomere, thus maintaining the original length of chromosome. Cem line cells exhibit active enzyme telomerase which functions to maintain the stable length of telomere. Some of the cloned animals are reported prematurely getting old. It has to be ascertained whether the multipotent stem cells in the tissues of adult mammals have the original telomeres or shortened telomeres.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.159-168
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• 2004

Background : In recent years, numerous human tumor specific antigens such as melanoma antigen gene(MAGE) that is recognized by autologous cytotoxic T lymphocytes have been identified. MAGE is expressed in many human malignancies in various organs, such as lung, breast, stomach, esophagus and leukemia. Therefore MAGE has been studied widely for tumor diagnosis and immunotherapy. But, so far there were no clinical studies evaluating the role of MAGE in pleural effusion. We investigated the expression of MAGE in the patients with exudative pleural effusion for it's diagnostic utility and the results were compared with those of cytologic examinations. Methods : Diagnostic thoracentesis was performed in 44 consecutive patients with exudative pleural effusion during 6 months. We examined the expression of MAGE and cytology with the obtained pleural effusion. Expression of MAGE was interpreted by means of a commercial kit using RT-PCR method. Enrolled patients were divided into two groups such as malignant and benign and we analyzed its' sensitivity and specificity. Results : There were no significant differences between two groups in age, sex, white blood cell counts in pleural fluid, pleural fluid/serum protein ratio and pleural fluid/serum LDH ratio. The sensitivity and specificity of MAGE were 72.2% and 96.2% respectively and the positive predictive value and negative predictive value of MAGE were also 92.9% and 83.3% respectively. The sensitivity and negative predictive value of cytologic examinations were 66.7% and 81.3% respectively. There were no significant differences between sensitivities of MAGE and cytologic examinations but false positive result of MAGE was found in 1 case of tuberculous pleurisy. Conclusion : MAGE is a sensitive and specific marker for the differential diagnosis between benign and malignant effusion in patients with exudative pleural effusion. And MAGE would provide the equal sensitivity compared with that of cytologic examination in patients with malignant pleural effusion if 5mL of the pleural fluid is examined.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.487-494
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• 2008

Background: Chromosome 17p allele losses and mutations of p53 gene are the most common genetic abnormalities in lung cancer. The purposes of this study were to evaluate the factors associated with p53 protein overexpression and to evaluate its prognostic value in patients with pathologic stage I non-small cell lung cancer (NSCLC). Methods: This is a retrospective review for the patients who underwent surgical resection at Samsung Medical Center between Jan 2003 and Jun 2004. Immunohistochemical staining for p53 protein was performed on tumor tissues from patients with lung cancer. The p53 overexpression was evaluated in relation to age, sex, smoking history, histology and pathologic stage by univariate and multivariate analyses. The disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were analyzed using the Kaplan-Meier methods and the differences in DFS, DSS and OS were assessed by using the log-rank tests. Results: A total of 125 patients were included in the analysis and a median frequency of p53 expression in tumor tissue was 10%. The p53 overexpression (${\geq}10%$) was more common in squamous cell carcinoma (66%) than in adenocarcinoma (38%, p=0.002). The p53 overexpression was more common in pathologic stage IB (59%) than in IA (38%, p=0.002). Patients with p53-overexpressing tumor (27 years) smoked more years compared with those without it (20 years, p=0.032). Smoking history ${\geq}25$ pack-years was more common in patients with p53 overexpression (58%) than in those without it (38%, p=0.024). In the multivariate analysis, only histology was significantly associated with p53 overexpression. However, there were no significant differences of DFS, DSS and OS in relation to p53 status. Conclusion: The p53 overexpression was associated with histology, pathologic stage and smoking history in patients with pathologic stage I NSCLC. However, the p53 overexpression was not associated with patient's survival.

• Journal of Plant Biotechnology
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• v.32 no.3
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• pp.167-173
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• 2005

Three different cDNAS for cinnamate 4-hydroxylase (C4H) which are involved in the second step of the general phenylpropanoid pathway were isolated and designated as pc4h1 (1,755 bp), pc4h2 (1,655 bp), and pc4h3 (1,316 bp), respectively. The nucleotide sequence analysis revealed that both pc4h1 and pc4h2 clones encode polypeptides of 505 amino acids frame but pc4h3 clone was truncated at the 5'-end of coding region. The alignment of the deduced amino acid sequences showed that PC4H1 and PC4H2 are highly homologous (95.8% identical) with each other and contain three conserved domains which are typical in cytochrome P450 monooxygenase: proline-rich region, threonine-containing binding pocket for the oxygen molecule, and heme binding region. In addition, result of the phylogenic tree analysis revealed that both pepper C4Hs belong to Class 1. pc4h2 transcription was strongly induced in wounded fruit (400%) and root (200%) relative to its very low basal level but not in leaf or stem tissue. In case of pc4h1, the basal level of transcription was higher than pc4h2 but induction by wounding was lower in fruit and root while leaf and stem tissues did not respond to wounding. The basal level of pc4h3 transcripts was not, if any, detectable and response to wounding was not observed.