• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권2호
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• pp.91-99
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• 2012

Purpose: The aims of this study was to compare and evaluate the clinical characteristics, laboratory data, and prognosis for infants under age 1 year with CMV hepatitis and those with viral hepatitis of unknown etiology. Methods: A retrospective study was conducted of infants under age 1 year who were admitted with acute hepatitis. The exclusion criteria consisted of: autoimmune, genetic, metabolic, toxic, HAV, HBV, HCV, toxoplasma, rubella, herpes simplex, and Epstein-Barr virus. The 30 patients included were divided into two groups based on markers for CMV (IgM anti-CMV, CMV PCR in urine, CMV culture in urine). Results: The median age of patients (n=15) was 2.8 months. No other organ involvement was detected in any patient. Peak serum total bilirubin levels (n=4) ranged from 2.6 to 6.7 mg/dL. Peak serum ALT levels ranged from 51 to 1,581 IU/L. The duration of ALT elevation ranged from 1.5 weeks to 26 weeks (median 9 weeks). All had recovered in full without ganciclovir; there were no cases of hearing loss. The median age of controls (n=15) was 2.5 months. Peak serum total bilirubin levels (n=4) ranged from 1.6 to 9.1 mg/dL. Peak serum ALT levels ranged from 26 to 1,794 IU/L. No significant differences were observed between both groups regarding the peak serum ALT levels, peak serum total bilirubin levels, duration of hyperbilirubinemia and ALT elevation. Conclusion: Although it was not possible to differentiate congenital infection with perinatal infection in this study, the prognosis of patients with CMV hepatitis without other organ involvement was good without ganciclovir treatment.

• 대한약리학회지
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• 제25권1호
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• pp.115-134
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• 1989

Ganciclovir(GCV)와 Vidarabine(ara-A)을 단독으로 또는 동시에 HSV-1에 작용시켰을때 HSV-1의 복제, DNA합성 및 단백질 합성에 미치는 영향을 관찰할 목적으로 본 연구를 시행하였다. 본 실험에서는 4가지의 다른 HSV-1(Wild type KOS, $VCV^r$, $IUdR^r$, 및 $PAA^r5$)를 사용하였다. Virus복제에 미치는 항 virus약의 효과는 Vero 세포단층 배양에서 Yield reduction assay에 의해서 관찰하였다. 항 virus약의 virus DNA 합성에 미치는 영향은 NaI 밀도 구배초원심침전후 $H^3-$표지 virus DNA의 방사능에 의해서 관찰하였다. Virus 단백질의 합성에 미치는 항 virus약의 효과는 $^{35}S$를 표지한 후 polyacrylamide 겔 전기영동법, 자가방사기록법 그러고 virus bands의 음영농도주사법을 이용, 관찰하여 다음과 같은 결과를 얻었다. 1. GCV는 wild trype HSV-1 KOS와 $PAA^r5$의 복제를 강력하게 억제하였으나 $ACV^r$와 $IUdR^r$는 GCV에 대해서 중등도의 저항을 보였다. ara-A는 실험대상의 모든 HSV-(KOS, $ACV^r$, $IUdR^r$ 및 $PAA^r5$)의 복제에 대해서 거의 비슷하게 억제효과를 보였다. GCV와 ara-A 동시첨가는 KOS와 $PAA^r5$의 복제에 대해서 상승적인 억제효과를 보였고 $ACV^r$와 $IUdR^r5$의 복제에 대해서는 상가작용이하의 억제 효과를 보였다. 2. GCV또는 ara-A는 HSV-1감염 Vero세포에서 virus DNA의 합성을 유의하게 억제하였다. GCV와 ara-A의 동시첨가는 KOS 또는 $PAA^r5$ 감염세포에서 virus DNA 합성을 GCV 또는 ara-A를 단독 첨가하였을때 보다 현저하게 억제하였다. $ACV^r$ 또는 $IUdR^r$ 감염세포에서는 이런 현상을 관찰할 수 없었다. 3. Wild type HSV-1 감염세포에서 virus-단백질의 합성은 GCV, ara-A의 단독 첨가 또는 GCV와 ara-A의 동시첨가에 의해서 변경되지 않았다. Wild type HSV-1 감염말기에 GCV 또는 ara-A 단독 혹은 동시첨가에 의해서 virus 단백질의 합성은 경미하나마 유의성있게 증가하였다. Wild type HSV-1과 $PAA^r5$에 의한 단백질의 합성은 GCV 또는 ara-A 단독 첨가에 의해서 유의성있게 억제되었다. GCV또는 ara-A의 동시첨가는 GCV또는 ara-A를 단독으로 첨가했을 경우보다 단백질의 합성을 더욱 억제하였다. 이상의 실험결과로 보아 GCV와 ara-A의 동시사용은 HSV-1 혹은 ACV저항 DNA polymerase변이주인 $PAA^r5$에 대해서 상승적인 억제작용을 나타냈으며 이 효과는 virus DNA 합성 억제에 의한 것으로 생각된다. ACV저항 thymidine kinase 변이주인 $ACV^r$ 및 $IUdR^r$에 대해서는 ara-A가 유효하였다. 항 virus 약물에 의한 virus 단백질합성의 변화는 virus DNA 합성에 대한 억제효과에 인한 것으로 사려된다.

• BMB Reports
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• 제33권6호
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• pp.483-492
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• 2000

The Herpes simplex virus type 1 (HSV-1) strain F glycoprotein H (gH) gene in the pHLB-4 plasmid was recombinated into a baculovirus expression vector (lacZ-HcNPV) to construct a recombinant virus GH-HcNPV expressing gH. The sequences of gH and its expression were analyzed. The gH gene was located in the 6.41 kb BglII fragment. The open reading frame (ORF) of the gH gene was 2,517 bp and codes 838 amino acid residues. Insect cells infected with this recombinant virus synthesized a high level of the matured and gX-gH fusion protein with approximately 112 kDa. The fusion gH protein was localized on the membrane of the insect cells as seen by using immunofluorescence assay and accumulated in the cultured media by the SDS-PAGE and immunoprecipitation assays. The amino acid sequence presents additional characteristics compatible with the structure of a viral glycoprotein: signal peptide, putative glycosylation sites and a long C-terminal transmembrane sequence. Antibodies raised in mice to this recombinant protein recognized viral gH and neutralized the infectivity of HSV-1 in vitro. These results demonstrate that it is possible to produce a mature protein by gene transfer in eukaryotic cells, and indicate the utility of the HcNPV-insect cell system for producing and characterizing eukaryotic proteins. Furthermore, the neutralizing antibodies would appear to protect mice against HSV; accordingly, this particular recombinant protein may be useful in the development of a subunit vaccine.

• BMB Reports
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• 제36권5호
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• pp.514-519
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• 2003

The ribonucleotide reductase (RR) 2 gene of the HSV-2 strain G was cloned, sequenced, and expressed in an E. coli cell. The RR2 gene was located on the PstI 2.4 kb fragment, which was cloned and sequenced. The ORF of the gene was 1,011 bp and its termination codon was TAG; also, the CATATAA sequence was present in the promoter of the RR2 gene. A Poly A signal sequence (AATAAA) was found in the 3'-noncoding region. The RR2 proteins that were produced in the E. coli and Vero cells were confirmed using a Western blot analysis. SDS-PAGE revealed that the molecular weights of the fusion-RR2 that was produced in the E. coli cells were approximately 24 kDa and 38 kDa in the Vero cells. The RR2 proteins were soluble. The differences in the molecular weights might be due to modifications in the Vero cells.

• Annals of Clinical Neurophysiology
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• 제3권2호
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• pp.122-127
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• 2001

Background : Bell's palsy(BP) is defined as an idiopathic peripheral facial paralysis of sudden onset and account more than 50% of facial paralysis. It's etiology is unclear, but herpes simplex virus type-1(HSV-1) has been the most suspicious causative agent of BP that ever been studied. We evaluated the effect of add-on acyclovir in acute stage of BP. Methods : Subject consisted of 35 patients who developed acute idiopathic unilateral facial nerve palsy(16 men and 19 women with age 9-78 years old). The treatments were started within 10 days after onset of BP. Facial nerve function was assessed by the House-Brackman facial nerve grading scale and facial nerve conduction study including blink reflex. Follow-up evaluation were made 2 month after onset. Twenty of 35 patients were treated with combined therapy of acyclovir and prednisone. As a control group, 15 patients were treated with prednisone only. We compared the improvement of neurologic defects at recovery phase. Results : Compared with two groups, difference in grading scale at recovery phase is statistically significant(p<0.01). So, acyclovir-prednisone group showed a significant improvement in grading scale at recovery phase compared with prednisone group. Conclusion : We identified the benefits of add-on acyclovir in the acute stage of BP.

• Journal of Microbiology and Biotechnology
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• 제11권2호
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• pp.234-241
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• 2001

The C-terminal 393 bp region of the human interleukin-16 (IL-16) gene was cloned and expressed in E. coli along with mammalian cell lines. Recombinant IL-16 expressed from E. coli was 22 kDa on SDS-PAGE and showed 260% of chemoattractant activity at a concentration of $0.1\;{\mu}g/ml$. HeLa, COS, and Neuro-2a cells were transduced by recombinant retrovirus vector pLNC/IL-16/IRES/TK and the intracellular and secreted amounts of IL-16 produced by HeLa/IL-16/TK, COS/IL-16/TK, and Neuro-2a/IL-16/TK cells were determined by enzyme-linked immunosorbent assay (ELISA). HeLa/IL-16/TK $(1{\times}10^5)$ and COS/IL-16/TK $(1{\times}10^5)$ cells secreted 36.1 and 13.3 ng of IL-16 for 48 h, respectively. Forty-nine ng and 86.4 ng of IL-16 remained in the cell lysates of HeLa/IL-16/TK and COS/IL-16/TK. Intracellular and secreted amounts of IL-16 from Neuro-2a/IL-16/TK $(5{\times}10^5)$ cells during 24 h cultivation were 50 ng and 3.3 ng, respectively. Also, HeLa and COS cells wee stably transfected with mammalian expression vector pCRIII/IL-16. Both culture media and cell lysates prepared from HeLa/IL-16 cells and COS/IL-16 cells showed chemoattractant activity ranging from 190% to 460% as compared to the control experiment. Expression of the herpes simplex virus thymidine kinase (HSV0tk) gene in pLNC/IL-16/ IRES/TK bicistronic retroviral expression vector was verified by performing a genciclovir (GCV) sensitivity assay. Finally, IL-16 repressed Tat-transactivated human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) promoter activity.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.43-50
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• 1998

Niosomes are vesicles formed from synthetic non-ionic surfactants, offering an alternative to chemically unstable and expensive liposomes as a drug carrier. Non-ionic surfactant and cholesterol mixture film leads to the formation of vesicular system by hydration with sonication method. The formation of niosome was ascertained by negative staining of TEM. The entrapment efficiency of niosomal suspension was gradually increased with increasing the ratio of cholesterol to surfactant. It was found that the niosome with 6 : 4 (polyoxyethylene 2-cetyl ether: cholesterol) ratio was more stable than those with other ratios. The topical application of acyclovir(ACV) in the treatment of herpes simplex virus type 1(HSV-1) skin disease has a long history. There are an increasing number of reports, however, in which topical ACV therapy is not as effective as oral administration. Lack of efficacy with topical ACV has been hypothesized to reflect the inadequate delivery of drug to the skin. We investigated the permeation of niosome containing $[^{3}H]ACV$ in hairless mouse skin using Franz diffusion cell model. Permeation coefficient(P) of aqueous ACV was $6.7{\times}10^{-4}\;(cm/hr)$ and that of ACV in niosome was $23.4{\times}10^{-4}\;(cm/hr)$, suggesting about 3.5 times increase in the transdermal permeation.

• 대한의생명과학회지
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• 제8권4호
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• pp.257-268
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• 2002

Chronic infection and inflammation have recently been implicated as important etiologic agents of atherosclerosis. Several agents have been suggested as possible candidates including cytomegalovirus (CMV), herpes simplex vims type 1 (HSV-1), Epstein-Barr virus (EBV), Chlamydia pneumoniae, and Helicobacter pylori. We evaluated the relationship between cytornegalovirus infection and atherosclerosis by in situ hybridization and polymerase chain reaction (PCR). We examined 23 subjects with atherosclerosis and 10 matched control subjects without atherosclerosis. CMV was detected by in situ hybridization in 60.9% (14/23) of aorta and 42.9% (9/21) of coronary arteries in subjects with atherosclerosis. It was also detected by PCR in 65.2% (15/23) of aorta and 52.4% (11/21) of coronary arteries. CMV was detected on areas showing early or advanced atheromatous changes. Cells morphologically identical to smooth muscle cells, endothelial cells, lymphocytes, fibroblasts, and Schwann cells were positively reacted with the CMV probe. However. none of the cells to which the probe hybridized contained inclusion bodies, thus strongly suggesting that the arterial wall may be a site of CMV latency. This result Indicates that CMV may potentially play a direct or indirect role in the pathogenesis of human atherosclerosis.

• 동의생리병리학회지
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• 제18권4호
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• pp.1061-1070
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• 2004

Chronic oral aphthae, recurrent ulcer and uveitis are the three main festations of Behcet's disease(BD). The aetiopathogenesis of Behcet's disease is still obscure, but herpes simplex virus is one of the possible casual factors. Gamchosasim-tang (Gancaoxiexin-tang), Banhasasim-tang(Banxiaxiexin-tang) and Saenggangsasim-tang( Shengjiangxiexin-tang) are traditional medication in Oriental medicine, that has been used to treat inflammatory disease. Especially, Gamchosasim-tang used to treat Behcet's disease like symptoms. ICR mice were used for this study. The earlobe of the mice were scratched with a needle, then inoculation with 1.0×10/sup 6/ plaque forming units/㎖ of HSV type I. Virus inoculation was performed twice with 10 day interval, followed by 16 weeks of observation. Using the HSV-induced Behcet's disease mouse model, kinds of Sasim-tang were administered variously before and after inoculation. In order to. classify the symptomatic mice as having Behcet's disease like symptoms. We followed the revised Japanese classification with minor modifications. Ulceration of the mice were monitored. In addition, spleen cytokine expression were measured by polymerase chain reaction, ELISA. HSV DNA was detected in HSV inoculation mice. HSV-induced mice treated with kinds of Sasim-tang showed improvement in symptom. In RT-PCR results, IFN-γ was expressed for all groups, IL-2 was expressed for the treated groups, and IL-10 was also expressed. IL-4 was expressed nothing. In ELISA, IL-2 was increased for GSST 2, BSST 2, GSST 2, GSST3 and INF-γ was increased for GSST 2, BSST 2, SSST 2, SSST 3. This model suggest the possible role of immune response to viral infection in the development and activation of Behcet's disease.

• Genomics & Informatics
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• 제21권2호
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• pp.26.1-26.9
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• 2023

Stevens-Johnson syndrome (SJS) produces a severe hypersensitivity reaction caused by Herpes simplex virus or mycoplasma infection, vaccination, systemic disease, or other agents. Several studies have investigated the genetic susceptibility involved in SJS. To provide further genetic insights into the pathogenesis of SJS, this study prioritized high-impact, SJS-associated pathogenic variants through integrating bioinformatic and population genetic data. First, we identified SJS-associated single nucleotide polymorphisms from the genome-wide association studies catalog, followed by genome annotation with HaploReg and variant validation with Ensembl. Subsequently, expression quantitative trait locus (eQTL) from GTEx identified human genetic variants with differential gene expression across human tissues. Our results indicate that two variants, namely rs2074494 and rs5010528, which are encoded by the HLA-C (human leukocyte antigen C) gene, were found to be differentially expressed in skin. The allele frequencies for rs2074494 and rs5010528 also appear to significantly differ across continents. We highlight the utility of these population-specific HLA-C genetic variants for genetic association studies, and aid in early prognosis and disease treatment of SJS.