• Asian-Australasian Journal of Animal Sciences
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• 제18권5호
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• pp.723-727
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• 2005

Ghrelin is a novel growth-hormone-releasing acylated peptide, which has been purified and identified in rat stomach. In the present study, the full-length sequence of bovine ghrelin cDNA was cloned by RT-PCR. The bovine ghrelin cDNA sequence derived in the present study included a 348 bp open reading frame and a 137 bp 3'UTR. The putative amino acid sequence of bovine prepro-ghrelin consisted of 116 amino acids, which contained the 27-amino acid ghrelin. The sequence analysis of the bovine ghrelin gene revealed that an intron existed between Gln$^{13}$ and Arg$^{14}$ of ghrelin. This exon-intron boundary matched the GT-AG rule of the splicing mechanism. Compared with rats, which have two tandem CAG sequences in the 3'end of intron, bovine ghrelin genome has only one CAG sequence. Therefore, although rats can produce 28 amino acid-ghrelin and 27 amino acid-des-Gln$^{14}$-ghrelin by alternative splicing, ruminant species, including bovines, might be able to produce only one type of ghrelin peptide, des-Gln$^{14}$-ghrelin. The influence of aging on plasma ghrelin concentration was also examined. Plasma ghrelin concentration increased after birth to approximately 600 days of age, and then remained constant.

• Journal of Genetic Medicine
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• 제4권1호
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• pp.22-37
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• 2007

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases, clinically and genetically heterogeneous, characterized by degeneration of spinocerebellar pathways with variable involvement of other neural systems. At present, 27 distinct genetic forms of SCAs are known: SCA1-8, SCA10-21, SCA23, SCA25-28, DRPLA (dentatorubral-pallidoluysian atrophy), and 16q-liked ADCA (autosomal dominant cerebellar ataxia). Epidemiological data about the prevalence of SCAs are restricted to a few studies of isolated geographical regions, and most do not reflect the real occurrence of the disease. In general a prevalence of about 0.3-2 cases per 100,000 people is assumed. As SCA are highly heterogeneous, the prevalence of specific subtypes varies between different ethnic and continental populations. Most recent data suggest that SCA3 is the commonest subtype worldwide; SCA1, SCA2, SCA6, SCA7, and SCA8 have a prevalence of over 2%, and the remaining SCAs are thought to be rare (prevalence <1%). In this review, we highlight and discuss the SCA7. The hallmark of SCA7 is the association of hereditary ataxia and visual loss caused by pigmentary macular degeneration. Visual failure is progressive, bilateral and symmetrical, and leads irreversibly to blindness. This association represents a distinct disease entity classified as autosomal dominant cerebellar ataxia (ADCA) type II by Harding. The disease affectsprimarily the cerebellum and the retina by the moderate to severe neuronal loss and gliosis, but also many other central nervous system structures as the disease progresses. SCA7 is caused by expansion of an unstable trinucleotide CAG repeat in the ATXN7 gene encoding a polyglutamine (polyQ) tract in the corresponding protein, ataxin-7. Normal ATXN7 alleles contain 4-35 CAG repeats, whereas pathological alleles contain from 36->450 CAG repeats. Immunoblott analysis demonstrated that ataxin-7 is widely expressed but that expression levels vary among tissues. Instability of expanded repeats is more pronounced in SCA7 than in other SCA subtypes and can cause substantial lowering of age at onset in successive generations termed ‘anticipation’ so that children may become diseased even before their parents develop symptoms. The strong anticipation in SCA7 and the rarity of contractions should have led to its extinction within a few generations. There is no specific drug therapy for this neurodegenerative disorder. Currently, therapy remains purely symptomatic. Cellular models and SCA7 transgenic mice have been generated which constitute valuable resources for studying the disease mechanism. Understanding the pathogenetic mechanisms of neurodegeneration in SCAs should lead to the identification of potential therapeutic targets and ultimately facilitate drug discovery. Here we summarize the clinical, pathological, and genetic aspects of SCA7, and review the current understanding of the pathogenesis of this disorder. Further, we also review the potential therapeutic strategies that are currently being explored in polyglutamine diseases.

• Clinical and Experimental Pediatrics
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• 제45권5호
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• pp.659-663
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• 2002

저자들은 상염색체 우성으로 유전되는 경한 저색소성 소구성 빈혈을 보이고 ${\beta}$ 유전자의 127번째 코돈 이 CAG에서 CGG로 치환되는 과오돌연변이로 인하여 매우 불안정한 베타 사슬 변이체를 만드는 우성유전 베타 지중해빈혈을 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• 생명과학회지
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• 제10권6호
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• pp.630-639
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• 2000

The gastric pathogen Helicobacter pylori(H. pylori) establishes long-term chronic infection that can lead to atrophic gastritis, intestinal metaplasia, and gastric cancer. H. pylori, which express cytotoxic genes is now recohnized as a cause of peptic ulcer and is also a major risk factor for the development of gastric adenocarcinoma. We performed this study 1) to assess the detection rate of H. pylori according to direct investigation of bacteria of gastric biopsy specimen and two serologic tests of GAP test and Helico blot 2.0 system in the symptomatic and non-symptomatic group 2) to evaluate and compare the efficacy of two serologic tests of GAP test and Helico blot 2.0 system for the diagnosis of H. pylori infection. Forty-nine patients were positive for H pylori infection based on direct investigation of bacteria by histology. The detection rates of H. pylori infection based on direct investigation of bacteria by histology. The detection rates of H. phlori were significantly lower in gastric cancer than in other gastroduodenal disease(p<0.05). The concordance of two serologic tests of GAP test and Helico blot 2.0 system is poor. There was no statistically significant difference between the expression rate of CagA and VacA in the symptomatic and non-symptomatic group. Although Helico blot 2.0 system may not displace GAP test, it was a very sensitive serologic test for the diagnosis of H. pylori infection and it was used to detect IgG antibodies to H. pylori-specific antigens, including CagA, VacA and the various urease subunit. Our data suggest that further investigation is needed to determine whether or not the serologic expression of cytotoxic gene may be clinical usefulness of diagnostic methods in the gastroduodenal disease.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2000년도 국제심포지움
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• pp.7-8
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• 2000

Transgenic animals are very useful for scientific, pharmaceutical, and agricultural purposes. In livestock, transgenic technology has been used forthe genetic alteration of farm animals, the production of human proteins inlarge quantities in the milk of transgenic farm animals, and the generation of animals with organs suitable for xenotransplantation. To date, the transfer of foreign genes into farm animals has been performed mainly by microinjection of DNA into the pronuclei of fertilized eggs. However, the overall success rate of transgenic animals in livestock so far has been disappointingly low, eg., the efficiency is 0∼5% in swine, and less than 1% in sheep and cattle, compared with the rate in mice where 5% microinjected develop into transgenic animals. Recently, McGreath et al. (2000) have succeeded in producing the gene targeted sheep by the use of nuclear transfer from cultured somatic cells transfected with a foreign gene in vitro. However, we may need plenty of time until currently employ this method for gene transfer to farm animals. We have been studying to exploit the method for improving production efficiencies of transgenic animals with emphasis of its application to farm animals. The present paper describes three approaches that we have made in our laboratory to improve production efficiencies of transgenic animals, based on the DNA microinjection method. 1. Co-injection of restriction enzyme with foreign DNA into the pronucleus for elevating production efficiencies of transgenic animals. 2. Efficient selection of transgenic mouse embryos using EGFP as a marker gene. 3. Phenotypes of tansgenic mice expressing WAP/hGH-CAG/EGFP fusion gene produced by selecting transgenic embryos. 4. Efficient site-specific integration of the transgene targeting an endogenous lox like site in early mouse embryos.

• Annals of Clinical Neurophysiology
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• 제5권1호
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• pp.11-15
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• 2003

Backgrounds: Kennedy disease is a X-linked recessive disease characterized by bulbar symptoms, proximal muscle weakness, and gynecomastia. Methods: We analyzed clinical symptoms and performed electrodiagnostic studies on 6 patients. Results: We found following features: 1) proximal muscle weakness 2) bulbar symptoms, as dysarthria, facial and tongue atrophy 3) hyporeflexia or areflexia 4) fasciculations, predominantly on face, and proximal upper extremities 5) decreased sensory nerve action potentials(SNAPs) 6) chronic neurogenic changes in needle EMG. Conclusions: Kennedy disease is characterized by degenerative process of anterior horn cell and dorsal root ganglion without upper motor neuron dysfunction. Increased triple nucleotide CAG repeats(>38) in androgen receptor gene of Xp21 will confirm early stage of this disease.

• 대한미생물학회지
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• 제34권6호
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• pp.519-532
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• 1999

Helicobacter pylori is a causative agent of type B gastritis and plays a central role in the pathogenesis of gastroduodenal ulcer and gastric cancer. To elucidate the host-parasite relationship of the H. pylori infection on the basis of molecular biology, we tried to evaluate the genomic diversity of H. pylori. An ordered overlapping bacterial artificial chromosome (BAC) library of a Korean isolate, H. pylori 51 was constructed to set up a genomic map. A circular physical map was constructed by aligning ApaI, NotI and SfiI-digested chromosomal DNA. When the physical map of H. pylori 51 was compared to that of unrelated strain, H. pylori 26695, completely different restriction patterns were shown. Fifteen known genes were mapped on the chromosome of H. pylori 51 and the genetic map was compared with those of strain 26695 and J99, of which the entire genomic sequences were reported. There were some variability in the gene location as well as gene order among three strains. For further analysis on the genomic diversity of H. pylori, when comparing the genomic structure of 150 H. pylori Korean isolates with one another, genomic macrodiversity of H. pylori was characterized by several features: whether or not susceptible to restriction digestion of the chromsome, variation in chromosomal restriction fingerprint and/or high frequency of gene rearrangement. We also examined the extent of allelic variation in nucleotide or deduced amino acid sequences at the individual gene level. fucT, cagA and vacA were confirmed to carry regions of high variation in nucleotide sequence among strains. The plasticity zone and strain-specific genes of H. pylori 51 were analyzed and compared with the former two genomic sequences. It should be noted that the H. pylori 51-specific sequences were dispersed on the chromosome, not congregated in the plasticity zone unlike J99- or 26695-specific genes, suggesting the high frequency of gene rearrangement in H. pylori genome. The genome of H. pylori 51 shows differences in the overall genomic organization, gene order, and even in the nucleotide sequences among the H. pylori strains, which are far greater than the differences reported on the genomic diversity of H. pylori.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.147-155
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• 2014

Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.

• Asian-Australasian Journal of Animal Sciences
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• 제19권2호
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• pp.153-159
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• 2006

A 2,656 bp fragment of chicken ghrelin gene was cloned and SNPs were detected by PCR-RFLP and Allele Specific PCR (ASP) in 12 Chinese indigenous chicken breeds and a commercial chicken population. The results showed that there were 23 base variations and an amino acid change ($Gln{\rightarrow}Arg$) in cloned chicken ghrelin gene. Three SNPs were confirmed in 13 populations and associations between this gene and growth traits of Tibetan chicken (TC) and Recessive White chicken (RW) were investigated. The results of haplotype analysis revealed that 26 haplotype genotypes were composed of eight haplotypes. The results of $x^2$ tests indicated that there were significant differences between genotypes or haplotype genotype frequencies in some of the breeds or sexes at 0.05 or 0.01 levels. The results of ANOVA revealed that there were significant differences between genotypes or haplotype genotypes on some growth traits of TC and RW chicken breeds at 0.05 or 0.01 levels. Multiple comparisons showed that there were significant associations between genotype CT at site 71 and some growth traits of two chicken breeds and between genotype AG at site 1,215 and body weight at 16 wk of two chicken breeds, and there was a significant association between haplotype genotype CAA/CAG and body weight and shank girth at 16 wk of two chicken breeds.

• Journal of Ginseng Research
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• 제46권4호
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• pp.572-584
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• 2022

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.