• Title/Summary/Keyword: Gross deletion

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Frequent Genetic Defects in the HIV-1 5'LTR/gag Gene in Hemophiliacs Treated with Korean Red Ginseng: Decreased Detection of Genetic Defects by Highly Active Antiretroviral Therapy

  • Cho, Young-Keol;Jung, You-Sun;Sung, Heung-Sup;Joo, Chul-Hyun
    • Journal of Ginseng Research
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    • v.35 no.4
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    • pp.413-420
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    • 2011
  • We investigated whether Korean red ginseng (KRG) and highly active antiretroviral therapy (HAART) affect the frequency of gross deletion in 5'LTR/gag in 20 hemophiliacs. This study is a prospective study in 20 hemophiliacs who were infected with Korean subclade B of HIV-1 from two cash-paid plasma donors in 1990. Over a 13-year period, we obtained 436 amplicons of 5'LTR/gag genes by nested polymerase chain reaction using 147 peripheral blood mononuclear cells. Of the 436 amplicons, 92 (21.1%) showed gross deletion in 5'LTR/gag. Despite of a 2.3-fold higher monthly dose of KRG intake, the frequency of gross deletion in 5'LTR/gag (16.4%) was significantly decreased during HAART compared with 28.1% prior to HAART (p<0.01). Gross deletion in 5'LTR/gag was 10% more detected on KRG-therapy than prior to KRG-therapy (p<0.05). In addition, we also obtained 28 amplicons containing premature stop codon or isoleucine at initiation codon of 254 amplicons sequenced on KRG intake (7.5%) or HAART (13.6%) compared with 0% before KRG intake. These findings indicate that high frequency of gross deletion in 5'LTR/gag and genetic defects prior to HAART are significantly associated with KRG intake and the detection of gross deletion in 5'LTR/gag is decreased by HAART.

Dosage and Duration Effects of Korean Red Ginseng Intake on Frequency of Gross Deletions in the nef Gene

  • Cho, Young-Keol;Jung, You-Sun
    • Journal of Ginseng Research
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    • v.34 no.3
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    • pp.219-226
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    • 2010
  • In the present study, we investigated whether a gross deletion in the nef gene ($g{\Delta}nef$) is induced by Korean red ginseng (KRG) intake. Ten patients were treated with KRG powder for 3 years in the absence of antiretroviral drug therapy. On average, $3,555{\pm}1,042\;g$ KRG was administered per person over $36.1{\pm}2.4$ months. There was a mild decrease in CD4 T cell count ($75{\pm}110/{\mu}L$) over the $36.1{\pm}2.4$ months (p = 0.059). We obtained 355 nef amplicons using 71 peripheral blood mononuclear cell samples over a 3-year period. All ten patients exhibited g${\Delta}$nef (range, 3.2 to 45.9%). At baseline, 3 of 78 amplicons (3.8%) exhibited $g{\Delta}nef$, whereas 18.8% (52/277) revealed $g{\Delta}nef$ during KRG-intake (p<0.001). The proportion of $g{\Delta}nef$ was significantly correlated with monthly dose of KRG (r=0.89, p<0.001). The median time for first detection of $g{\Delta}nef$ was 13 months. In conclusion, our data show that $g{\Delta}nef$ is inducible by KRG intake and its proportion is dependent on the duration of KRG intake and dose of KRG.

Impact of HIV-1 subtypes on gross deletion in the nef gene after Korean Red Ginseng treatment

  • Cho, Young-Keol;Kim, Jung-Eun;Lee, Jinny
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.731-737
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    • 2022
  • Background: The number of primary human immunodeficiency virus (HIV)-1 non-B subtype infections (non-B) and that of reports regarding the differences in the pathogenesis of subtype B and non-B infections are increasing. However, to the best of our knowledge, there have been no reports on gross deletion in the nef gene (g∆nef) in non-B infections. Methods: To determine whether there is a difference in the change in CD4+ T cells after treatment with Korean Red Ginseng (KRG) between patients with subtype B and non-B infections, we retrospectively analyzed and compared the annual decrease in CD4+ T cells (AD) and the proportion of g∆nef in 77 patients who were followed for more than 10 years in the absence of combination antiretroviral therapy. Results: Overall, AD was significantly faster in patients with non-B infections than in those with subtype B infections. Survival analysis showed that the survival probability was significantly higher in subtype B than in non B-infected patients. These differences mainly resulted from significant differences in the amount of KRG and age. In the patients treated with KRG, there was a significant correlation between the amount of KRG and the AD in both subtypes. Interestingly, there was a significant correlation between the amount of KRG and the proportion of g∆nef in patients infected with subtype B, but not in those infected with non-B. The same phenomenon was observed when the KRG dose was adjusted. Conclusion: Our results suggest that non-B may be biologically more stable than subtype B.

Genetic defects in the nef gene are associated with Korean Red Ginseng intake: monitoring of nef sequence polymorphisms over 20 years

  • Cho, Young-Keol;Kim, Jung-Eun;Woo, Jun-Hee
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.144-150
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    • 2017
  • Background: The presence of gross deletions in the human immunodeficiency virus nef gene ($g{\Delta}nef$) is associated with long-term nonprogression of infected patients. Here, we investigated how quickly genetic defects in the nef gene are associated with Korean Red Ginseng (KRG) intakein 10 long-term slow progressors. Methods: This study was divided into three phases over a 20-yr period; baseline, KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene amplicons were obtained using reverse transcription polymerase chain reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and these were then sequenced. The proportion of $g{\Delta}nef$, premature stop codons, and not in-frame insertion or deletion of a nucleotide was compared between three phases, control, and ART patients. Results: The proportion of defective nef genes was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p < 0.01). Small in-frame deletions or insertions were significantly more frequent among patients treated with KRG alone compared with controls (p < 0.01). Significantly fewer instances of genetic defects were detected in samples taken during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected were $g{\Delta}nef$ and small in-frame deletions after 7 mo and 67 mo of KRG intake, respectively. Conclusion: KRG treatment might induce genetic defects in the nef gene. This report provides new insight into the importance of genetic defects in the pathogenesis of AIDS.

Korean Red Ginseng-intake has Definite Clinical Usefulness and causes Nef Gene Variation including High Frequency of Deletion

  • Cho Young Keol;Lee Hee Kyung;Ahn Sun Hee;Lee Hee Jung;Nam Ki Yeul
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.185-211
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    • 2002
  • We have found many beneficial effects of the long-tenn intake of Korean red ginseng (KRG) in human immunodeficiency virus (HIV) type-I infected patients, including the maintenance of CD4+ T cell count for 10 years with KRG only and the delayed development of resistance mutation to ZDV. In this study, to investigate whether KRG-intake could affect the clinical progression and nef gene variation, we determined 200nef sequences from 70 patients. Follow-up period was $8.8{\pm}2.9$ years and annual decrease in CD4+T cell was $41{\pm}57/ul.$ Nested polymerase chain reaction (PCR) and direct sequencing were perfonned with peripheral blood mononuclear cells (PBMC) obtained at times during the study period. First, there was a significant correlation between survival duration and duration of KRG-intake $(36.8{\pm}38$ months)(P=0.000). There were significant correlations between the last NefProg score and CD4+ T cell count (r= 0.208, P<0.05) and annual decrease in CD4+ T cell count (r =0.346, P<0.01) in 70 patients. In addition, there were significant correlations between KRG-intake and annual decrease (r= 0.323, P<0.01), and the CD4+ T cell count itself (r=0.229, p<0.05). Furthennore, there was also a mild significance between the NefProg score and the duration of KRG-intake in only SP and RP (n=30, r=-0.281, P=0.067). In addition, we detected various defects in 21 patients $(30.0\%),$ not including 5 premature stop codons. Ten $(12.5\%)$ patients showed repeated deletion of an amino acid. Four of 10 patients were gross deletions and they were treated with KRG for more than 20 months. The number of patients with repeated gross deletions was significantly higher in the order of slow progressors $(18\%)$, typical progressors($3\%$), and rapid progressors($0\%$) (P<0.05). We also observed that long-tenn intake of KRG might make the change from A or D to T at position 54 and decrease NefProg score. Taken together, our results show clear evidence that the long-term intake of KRG has effects on nef gene variation as well as definite clinical usefulness.

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Homeobox Gene (OSH1) Expression in Embryonic Mutants of Rice (Oryza sativa L.)

  • Hong, Soon-Kwan;Lee, Sang-Lyung;Shin, Young-Boum;Yoon, Kyung-Min;Kim, Nam-Soo
    • Animal cells and systems
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    • v.2 no.1
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    • pp.81-86
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    • 1998
  • Recent identification and characterization of plant homeobox genes suggest that they play important roles in morphogenetic events. OSH1, one of the rice homeobox genes, is thought to be related to organ development since the changes of OSH1 gene expression cause morphological abnormalities of leaves by the ectopic expression and is expressed during early embryogenesis. In this experiment, the expression pattern of OSH1 was analyzedinmutants by in situ hybridization, and OSH1's potential as a molecular marker was explored. Region-specific expression of OSH1 during early embryogenesis shows that OSH1 could be used as a molecular marker for characterizing embryo mutants. Although several organless and shootless mutants showed normal expression of OSM1, some mutants exhibited abnormal expression patterns. In a minute organless cle1-1 embryo whose epidermis resembled morphologically the epithelium of scutellum, OSH1 expression was limited to a small basal region. This expression pattern suggests the gross deletion of the basal part. In a radicleless mutant, odm115, OSH1 expression was detected in a basal region instead of subcentral region of the ventral side. Together with other characteristics (short embryo and normal adventitious roots), odm115 was estimated to be derived from the deletion of basal region. Among five shootless mutants, three showed normal expression of OSH1. In the shl2 embryo, no expression of OSH1 was observed. In the shl1 embryo, however, OSH1 expression was extended to a dorsal side, indicating that SHL2 might be related to dorsoventral patterning. The above results of in situ hybrydization clearly indicate that OSH1 can be utilized as a marker for characterizing gene functions of embryo mutants.

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Dynamic Susceptibility Contrast (DSC) Perfusion MR in the Prediction of Long-Term Survival of Glioblastomas (GBM): Correlation with MGMT Promoter Methylation and 1p/19q Deletions

  • Kwon, Yong Wonn;Moon, Won-Jin;Park, Mina;Roh, Hong Gee;Koh, Young Cho;Song, Sang Woo;Choi, Jin Woo
    • Investigative Magnetic Resonance Imaging
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    • v.22 no.3
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    • pp.158-167
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    • 2018
  • Purpose: To investigate the surgical, perfusion, and molecular characteristics of glioblastomas which influence long-term survival after treatment, and to explore the association between MR perfusion parameters and the presence of MGMT methylation and 1p/19q deletions. Materials and Methods: This retrospective study was approved by our institutional review board. A total 43 patients were included, all with pathologic diagnosis of glioblastoma with known MGMT methylation and 1p/19q deletion statuses. We divided these patients into long-term (${\geq}60\;months$, n = 7) and short-term (< 60 months, n = 36) survivors, then compared surgical extent, molecular status, and rCBV parameters between the two groups using Fisher's exact test or Mann-Whitney test. The rCBV parameters were analyzed according to the presence of MGMT methylation and 1p/19q deletions. We investigated the relationship between the mean rCBV and overall survival using linear correlation. Multivariable linear regression was performed in order to find the variables related to overall survival. Results: Long-term survivors (100% [7 of 7]) demonstrated a greater percentage of gross total or near total resection than short-term survivors (54.5% [18 of 33]). A higher prevalence of 1p/19q deletions was also noted among the long-term survivors (42.9% [3 of 7]) than the short-term survivors (0.0% [0 of 36]). The rCBV parameters did not differ between the long-term and short-term survivors. The rCBV values were marginally lower in patients with MGMT methylation and 1p/19q deletions. Despite no correlation found between overall survival and rCBV in the whole group, the short-term survivor group showed negative correlation ($R^2=0.181$, P = 0.025). Multivariable linear regression revealed that surgical extent and 1p/19q deletions, but not rCBV values, were associated with prolonged overall survival. Conclusion: While preoperative rCBV and 1p/19q deletion status are related to each other, only surgical extent and the presence of 1p/19q deletion in GBM patients may predict long-term survival.

Pathological findings on encephalomyocarditis virus infections of swine in Korea (국내에서 발생한 돼지 뇌심근염 바이러스 감염증의 병리학적 관찰)

  • Park, Nam-yong;Ri, Chang-yeong;Chung, Chi-young;Kee, Hye-young;Bae, Seong-yeol
    • Korean Journal of Veterinary Research
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    • v.32 no.1
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    • pp.99-109
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    • 1992
  • Pathological studies by light and electron microscope were carried out on the twenty piglets naturally affected by encephalomyocarditis virus infection. Gross findings included pale or yellow, small necrotic foci on myocardium, together with pulmonary edema and liver congestion in some cases. On light microscopy, nonsuppurative interstitial endocarcitis, epicarditis and myocarditis, myocardial infarction, and dystrophic calcification or fibtosis were observed in heart. Perivascular cuffings, gliosis and nonsuppurative meningitis were appeared in brain. Focal or diffuse necrosis with mononuclear cell infiltration in lacrimal gland and multifocal necrosis in liver were observed in some cases. Congestion and edema of lung, hyperemia, hemorrhage and deletion of lymphocytes of lymph nodes and spleen were recognized. On electron microscopy, severe swelling and vacuolization of mitochondria and sarcoplasmic reticulum, large intracellular vacuolation and edema, separation and fragmentation of myofibrils were observed. Virus particles were seen in the sarcoplasm of degenerated cardiac muscle cell.

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