• Molecules and Cells
• /
• 제19권2호
• /
• pp.191-197
• /
• 2005

The human immunodeficiency virus type 1 (HIV-1) Tat protein transduction domain (PTD) is responsible for highly efficient protein transduction across plasma membranes. In a previous study, we showed that Tat-Cu,Zn-superoxide dismutase (Tat-SOD) can be directly transduced into mammalian cells across the lipid membrane barrier. In this study, we fused the human SOD gene with a Tat PTD transduction vector at its N- and/or C-terminus. The fusion proteins (Tat-SOD, SOD-Tat, Tat-SOD-Tat) were purified from Escherichia coli and their ability to enter cells in vitro and in vivo compared by Western blotting and immunohistochemistry. The transduction efficiencies and biological activities of the SOD fusion protein with the Tat PTD at either terminus were equivalent and lower than the fusion protein with the Tat PTD at both termini. The availability of a more efficient SOD fusion protein provides a powerful vehicle for therapy in human diseases related to this anti-oxidant enzyme and to reactive oxygen species.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권3호
• /
• pp.1177-1180
• /
• 2014

Background: Anogenital warts (AGWs) are common results of sexually transmitted infection (STI). Human papillomavirus (HPV) types 6 and 11, which are non-oncogenic types, account for 90% of the clinical manifestations. Although the quadrivalent HPV vaccine has been launched, AGW remains prevalent in some countries and shows association with abnormal cervical cytology. Objectives: To study the prevalence of abnormal cervical cytology (low grade squamous intraepithelial lesions or worse; LSIL+) in immunocompetent Thai women newly presenting with external AGWs. Materials and Methods: Medical charts of all women attending Siriraj STI clinic during 2007-2011 were reviewed. Only women presenting with external AGWs who were not immunocompromised (pregnant, human immunodeficiency virus positive or being on immunosuppressant drugs) and had not been diagnosed with cervical cancer were included into the study. Multivariate analysis was used to determine the association between the characteristics of the patients and those of AGWs and LSIL+. Results: A total of 191 women were eligible, with a mean age of $27.0{\pm}8.9$ years; and a mean body mass index of $20.6{\pm}8.9kg/m^2$. Half of them finished university. The most common type of AGWs was exophytic (80.1%). The posterior fourchette appeared to be the most common affected site of the warts (31.9%), followed by labia minora (26.6%) and mons pubis (19.9%). The median number of lesions was 3 (range 1-20). Around 40% of them had recurrent warts within 6 months after completing the treatment. The prevalence of LSIL+ at the first visit was 16.3% (LSIL 12.6%, ASC-H 1.1%, HSIL 2.6%). After adjusting for age, parity and miscarriage, number of warts ${\geq}5$ was the only factor associated with LSIL+(aOR 2.65, 95%CI 1.11-6.29, p 0.027). Conclusions: LSIL+ is prevalent among immunocompetent Thai women presenting with external AGWs, especially those with multiple lesions.

• IMMUNE NETWORK
• /
• 제1권2호
• /
• pp.135-142
• /
• 2001

Background: A large number of diseases occur in association with specific HLA-B or-C alleles. Recently a new gene, termed maj or histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown. However, it is structurally similar to HLA class I genes. MICA gene is polymorphic and is potentially associated with several diseases. Methods: To evaluate the association of MICA gene in Korean patients with human immunodeficiency virus 1 (HIV-1) infections, Polymerase chain reaction-Sequence specific primer (PCR-SSP) was done for MICA alleles in the extracellular exons, and a microsatellite analysis for GCT repeat polymorphisms in the TM exon was also completed. Results: In 199 Korean healthy controls, 7 alleles were observed and the frequencies for each allele were MICA008 (44.7%), MICA0 10 (34.2%), MICA002 (31.7%), MICA004 (23.6%), MICA0 12 (2 1.6%), MICA009 (19.6%), and MICA007 (6.5%). When 65 HIV seropositive patients were analyzed, MICA007 allele frequency was significantly higher than in controls (15.4% vs 6.5 %, RR=2.6, p<0.04). In contrast, the frequencies of other MICA alleles and microsatellite alleles in the transmembrane region of MICA gene were not significantly different between HIV seropositive patients and controls. The tight linkage between MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon was observed as follows; MICA002/A9, MICA004/A6, MICA007/A4, MICA008/A5.1, MICA0 10/A5, and MICA0 12/A4 in both groups. No significant difference between patients and controls was observed in the haplotype frequencies of MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon. Conclusion: The data suggest that immune functions related with MICA gene may affect a HIV infections.

• Journal of Preventive Medicine and Public Health
• /
• 제32권2호
• /
• pp.228-235
• /
• 1999

Objectives: Despite the importance of human immunodeficiency virus(HIV) transmission through heterosexual contact, the features of heterosexual transmission has not been well studied in Korea. So we conducted a cross sectional study to determine the transmission rates in married couples and assess risk factors for male to female heterosexual transmission of HIV. Methods: 169 HIV-infected males and their female sex partners were recruited from 1985 to tune 1998. We examined female sex partner's HIV infection status and interviewed male index partners and their female sex partners about demographic characteristics and sexual practices. We analysed heterosexual transmission rate by epidemiologic characteristics, disease status and sexual practices. And we assessed risk factors for HIV infection by univariate and multivariate analysis. Results: 30 female sex partners were infected at enrollment, yielding an transmission rate of 17.8%. Among couples who had used condoms consistently, none of the female sex partners was infected with HIV. In univariate analysis the significant risk factors were full blown AIDS status (OR=4.1, 95% CI: 1.49-11.43) and low CD4 T cell count of index partners at enrollment (OR=7.8, 95% CI: 2.19-27.80). In multivariate analysis HIV-1 RNA levels was significant risk factor when adjusted by CD4 T cell courts and mean sexual contacts per month (OR=19.2, 95% CI: 1.03-357.59) Conclusion: The risk of male to female heterosexual transmission increased with advanced stages of HIV infection in the index male partners.

• International Journal of Oral Biology
• /
• 제44권4호
• /
• pp.173-181
• /
• 2019

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with age-matched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

• Tuberculosis and Respiratory Diseases
• /
• 제57권2호
• /
• pp.101-117
• /
• 2004

현증 결핵환자가 감소하고, 면역억제환자가 증가하고 있는 국내 추세에서 잠복결핵(latent tuberculosis)의 진단 및 치료 지침이 필요한 실정이다. 그러나 결핵의 유병률, 발생률 그리고 비씨지 접종률 등이 외국과 다른 국내의 현실에서 현증이 없는 잠복결핵의 진단 및 치료에 대한 방침은 필연적으로 외국과 다를 수 밖에 없으며, 현 시점에 국내에서 이에 대한 자료가 불충분하여 국내의 환경에 적합한 근거 중심의 지침을 설정하기는 어려운 상황이다. 그러나 결핵의 기본 병태 생리를 근거로 하여 최소한 결핵균 감염 이후 결핵 발병의 위험성이 높은 대상 환자에서는 잠복결핵 진단을 위한 검사를 시행하여 치료 여부를 결정하여야 한다. 고위험군은 사람면역결핍바이러스(human immunodeficiency virus, HIV) 감염자, 장기이식환자, 면역억제제를 장기간 사용하는 환자, 6세 이하의 소아 중 최근 전염성 결핵환자 접촉자 등을 우선적으로 고려해야 한다. 미국은 발병 위험도의 고, 중, 저에 따라 투베르쿨린 검사(tuberculin skin test, Mantoux test)의 양성기준을 달리 하여 잠복결핵을 진단하고 있으나, 국내에는 아직 이에 대한 자료가 부족하므로 발병의 위험이 높은 상기 고위험군을 대상으로 하여 PPD RT-23 2TU (Tuberculin unit)를 이용한 피부반응검사에서 10mm이상의 경결(induration)이 생성되는 경우를 양성으로 정하고 추후 연구 결과에 따라 재조정이 필요하다. 그 동안은 투베르쿨린 검사 결과 5-10 mm 사이의 경결반응을 보이는 면역억제 환자에 대하여는 개별적으로 의사의 판단에 따라 잠복결핵의 진단 및 치료 여부를 결정한다. 그러나 면역억제제를 사용하는 등 결핵 발병의 고위험군에서는 피부반응검사상 음성이라도 과거 결핵 치료력이 없이 흉부사진상 명백하게 과거에 결핵을 앓은 흉터가 남아있는 경우(석회화된 1차 결핵 소견은 제외)에는 잠복결핵의 치료를 시행한다. 상기 잠복결핵의 진단 및 검사의 적응증은 최소한 시행하여야 할 경우를 나열한 것으로 이외의 환자에 대하여는 환경 및 대상에 따라 개별화되어야 한다. 치료제로는 isoniazid (INH) 9개월 매일 치료(최소 한 6개월 이상, HIV양성 환자인 경우는 9개월), rifa-mpicin (RFP) 4개월 치료 및 INH/RFP 3개월 매일 치료를 시행할 수 있다. 상기 치료가 어려운 경우에는 RFP/pyrazinamide (PZA) 2개월 매일 치료를 고려할 수 있으나 중증 간독성의 가능성에 대한 철저한 교육 및 추적검사가 필요하다. 향후 국내 환경의 변화 및 연구결과에 따라 추후 부족한 부분에 대한 지침의 재정립이 필요하다.

• Journal of Hospice and Palliative Care
• /
• 제20권1호
• /
• pp.8-17
• /
• 2017

종합적인 보건시스템을 지원하기 위한 완화의료정책의 개발과 강화가 세계적으로 강조되고 있다. 우리나라에서는 암정복 10개년 계획과 국가암관리종합계획의 기틀 하에 암정책의 일환으로, 호스피스완화의료정책이 시행되어왔고, 2003년 암관리법(Cancer Control Act)을 제정하여 법적 근거를 마련하였으며, 최근 호스피스 완화 의료 및 임종과정에 있는 환자의 연명의료결정에 관한 법을 제정하여 시행할 예정이다. 호스피스완화의료정책의 대상은 최근 관련법의 제정에 따라, 말기암환자에서 암(Cancer), 후천성면역결핍증(Acquired immune deficiency syndrome, AIDS), 만성 폐쇄성 호흡기질환(Chronic Obstructive Pulmonary Disease, COPD), 만성간경화(Chronic Liver Disease/Live Cirrhosis) 등으로 확대되었고, 급여체계는 2015년에 모든 의료기관에 일당 정액수가와 행위별 수가의 복합지불방식으로 완화의료 건강보험제도가 시행되었다. 전달체계관련 건강보험제도는 입원형과 자문형, 그리고 가정형으로 구분되고, 완화의료전문기관의 지정 평가 지원제도가 운영되고 있으며, 재원체계는 건강보험기금과 국가지원금으로 조달되고 있다. 호스피스 완화의료 관련법의 시행에 앞서, 정책대상의 사회적 합의가 요구되며, 낮은 급여체계의 현실화, 민관협력을 통한 호스피스완화의료 표준설정과 전문요원양성, 질 관리 및 평가체계정립, 그리고 장기요양보험과 호스피스기금 등을 활용한 안정적인 재정체계를 마련해야 할 것이다.

• Tuberculosis and Respiratory Diseases
• /
• 제68권4호
• /
• pp.218-225
• /
• 2010

Background: Bronchoalveolar lavage (BAL) is a useful technique to recover lower airway fluid and cells involved in many respiratory diseases. Miliary tuberculosis is potentially lethal, but the clinical manifestations are nonspecific and typical radiologic findings may not be seen until late in the course of disease. In addition, invasive procedures are often needed to confirm disease diagnosis. This study analyzed the cells and the T-lymphocyte subset in BAL fluid from patients with miliary tuberculosis to determine specific characteristics of BAL fluid that may help in the diagnosis of miliary tuberculosis, using a less invasive procedure. Methods: On a retrospective basis, we enrolled 20 miliary tuberculosis patients; 12 patients were male and the mean patient age was $40.5{\pm}16.2$ years. We analyzed differential cell counts of BAL fluid and the T-lymphocyte subset of BAL fluid. Results: Total cells and lymphocytes were increased in number in the BAL fluid. The percentage of CD4+ Tlymphocytes and the CD4/CD8 ratio in BAL fluid were significantly decreased and the percentage of CD8+ T-lymphocytes was relatively higher. These findings were more prominent in patients infected with the human immunodeficiency virus (HIV). In the HIV-infected patients, the proportion of lymphocytes was significantly higher in BAL fluid than in peripheral blood. There were no significant differences between the BAL fluid and the peripheral blood T-lymphocytes subpopulation. Conclusion: BAL fluid in patients with miliary tuberculosis demonstrated lymphocytosis, a lower percentage of CD4+ T-lymphocytes, a higher percentage of CD8+ T-lymphocytes, and a decreased CD4/CD8 ratio. These findings were more significant in HIV-infected subjects.

• 대한수의학회지
• /
• 제46권1호
• /
• pp.7-12
• /
• 2006

We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

• 농촌의학ㆍ지역보건
• /
• 제40권2호
• /
• pp.72-79
• /
• 2015

본 연구는 HIV병 사망자 중 HIV병과 결핵이 동반사망한 분율을 조사하고 그 관련 요인을 분석하였다. 2002년부터 2010년까지 사이에 HIV병 사망자는 모두 774명으로 결핵이 동반사망한 분율은 10.1%로 나타났다. 그런데 이러한 분율은 2005년부터 2007년 사이에 16.3%까지 치솟았지만 2008년부터 2010년 사이에는 4%까지 감소하는 경향을 보였다. 또한 HIV-결핵 동반사망 분율은 젊은 계층에서 더 높았고 배우자가 있는 그룹과 교육을 잘 받은 그룹에서는 유의하게 낮은 경향을 보였다. 이처럼 활동성이 높은 젊은층에서 HIV-결핵 동반사망 분율이 높고 사회경제적 안정계층에서 HIV-결핵 동반사망 분율이 낮은 것은 비슷한 해외 연구에서도 유사하게 나타나고 있어 HIV-결핵 동반사망의 예방 가능성을 시사한다. 한국은 다행히 점차 HIV-결핵 동반사망 분율이 낮아지고 있어 HIV감염자에 대한 결핵 예방사업의 효과가 나타나고 있음을 시사하고 이후 이러한 지표의 지속적인 모니터링이 필요함을 보여주고 있다.