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Unusual outcome of in utero infection and subsequent postnatal super-infection with different PCv2b strains

virologica Sinica 2014年第3期29卷 176-182页

作者： Dipongkor Saha Uladzimir U.Karniychuk Liping Huang Marc Geldhof Merijn vanhee David J.Lefebvre Peter Meerts Richard Ducatelle Jan v.Doorsselaere Hans J.Nauwynck Laboratory of virology Department of Virology Parasitology and Immunology Faculty of Veterinary Medicine Ghent UniversityBelgium Brain Tumor Research Center Department of Molecular Neurosurgery Harvard Medical School and Massachusetts General Hospital 185 Cambridge StreetBoston MA-02114 USA Division of Experimental Therapeutics Toronto General Hospital Research Institute University Health NetworkToronto Canada Division of Swine Infectious Diseases Harbin Veterinary Research Institute The Chinese Academy of Agricultural Sciences Department of Health Care and Biotechnology KATHO Catholic University College of South-West FlandersBelgium CODA-CERvA Groeselenberg 99 1180 Ukkel Belgium Ablynx nv Technologiepark 219052 Zwijnaarde Belgium Department of Pathology Bacteriology and Poultry Diseases Faculty of Veterinary Medicine Ghent UniversityBelgium

vC2002, isolated from postweaning multisystemic wasting syndrome(PMWS)-affected pig, is a mixture of two porcine circovirus genotype 2b(PCv2b) viruses, K2 and K39. Preliminary experiments disclosed short-term adverse effects of K39, but not K2, on porcine foetuses. These findings led to the hypothesis that infection of immuno-incompetent foetuses with K2 confers a status of immunotolerance, and postnatal super-infection with K39 triggers PMWS. To explore this hypothesis, nine 55-day-old foetuses were inoculated in utero(three with K2-104.3TCID50, three with K39-104.3TCID50 and three with medium), and foeto-pathogenicity examined. At 21 days post-inoculation(dpi), K2 did not induce pathology, whereas pathological effects of K39 were evident. Twenty-four 45-day-old foetuses were subsequently inoculated to examine the long-term effect of K2, including six with K2-high dose-104.3TCID50, six with K2-low dose-102.3TCID50 and 12 mock-inoculated controls. Both doses resulted in five mummified foetuses and one live-born piglet each(69dpi). K2 was recovered from all mummies. K2 and K2-specific antibodies were not detected in serum of the two live-born piglets at birth, indicating full control of K2 infection. The K2-low dose-infected piglet was immunostimulated at day 2, but not the K2-high dose-infected piglet. Both non-stimulated and stimulated K2-infected piglets were super-inoculated with K39 at day 6 or 8(taken as 0 days post super-inoculation). Low viral replication was observed in the non-stimulated K2-K39 piglet(up to 103.3 TCID50/g; identified as K39). In contrast, viral replication was extremely high in the stimulated K2-K39 piglet(up to 105.6TCID50/g) and identified as K2, indicating that K2 infection is controlled during foetal life, but emerges after birth upon immunostimulation. However, none of the piglets showed any signs of PMWS.

关键词： PCv2 immunotolerance PMWS porcine foetuses

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慢性乙型肝炎自然史的研究

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中华肝脏病杂志 2002年第1期10卷 46-48页

作者：巫贵成周卫平赵有蓉郭树华王志毅邹淑碧张全海v400010 任红黄爱龙张定凤重庆医科大学病毒性肝炎研究所 400010

目的对乙型肝炎的自然史进行研究，为其预后判断、药物疗效的分析及药品经济学评估提供佐证。方法采用回顾性方法随访６～１８年前经肝穿病理组织学诊断的１８３例慢性乙型肝炎的远期转归、影响因素及其抗病毒治疗的远期作用。结果１... 详细信息

目的对乙型肝炎的自然史进行研究，为其预后判断、药物疗效的分析及药品经济学评估提供佐证。方法采用回顾性方法随访６～１８年前经肝穿病理组织学诊断的１８３例慢性乙型肝炎的远期转归、影响因素及其抗病毒治疗的远期作用。结果１８３例慢性乙型肝炎患者累计死亡２０例（１．９３％），发生肝硬化２２例（１１．０２％），肝癌１２例（６．５６％）。累计５、１０、１５年生存率分别为９７．２７％、９１．６２％和８４．４７％。因乙型肝炎及其并发症死亡者占死亡原因的８５．００％。累计肝癌５年、１０年、１５年发生率分别是０．３．１９％和１１．５６％。对照组２４７例死亡６例（２，４３％），无１例发展为肝硬化和肝癌。慢性乙型肝炎患者的死亡率是普通人群的４．５０倍。二者相比，肝硬化、肝癌和死亡的发生率差异均有显著性（Ｐ＜０．００５）。采用Ｃｏｘ回归分析，高龄、病理损害重、ＨＢｅＡｇ阳性是肝硬化的危险因素；高龄、病理损害重、男性是死亡的危险因素；未筛选出肝癌的危险因素。结论慢性乙型肝炎的远期预后不良。

关键词：慢性乙型肝炎病毒性肝炎自然史研究

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Retrospective study of HIv drug resistance in Mexican children with vertically transmitted infection

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World Journal of Pediatrics 2022年第7期18卷 505-510页

作者： Cristina de Jesus Herrera-Castillo Angelica Maldonado-Rodriguez Othon Rojas-Montes Ana Maria Cevallos JoséGuillermo vazquez-Rosales Rosalia Lira Infectious Diseases Department Pediatrics Hospital"Silvestre Frenk Freund"National Medical Center"Siglo ⅩⅪ".Mexican Social Sccurity Instiute(IMSS).Mexico City.Mexico Infectious and Parasitie Dise ases Medical Research Unit Pediatrics Hospital"Silvestre Frenk Freund"National Medical Center“Siglo ⅩⅪ”Mexican Social Security Institute(IMSS).Col.Cuauhtemoc.Av.Cuauhtemoc 33006720 Mexico CityMexico Departament of Molecular Biology and Biotechnology Biomedical Research InstituteNational Autonomous University of MexicoUNAMMexico City.Mexico

According to World Health Organization(WHO)estimates,in 2020,there were 1.8 million human immunodeficiency virus(HIv)-infected children below 15 years old living with HIv and 150,000 children who acquired the infection[1].Every year,110,000 children die as a consequence of acquired immune deficiency syndrome-related causes[2].As in adults,optimal management of infected children depends on early diagnosis and treatment with antiretroviral drugs based on their viral genotype.

关键词： infection diagnosis drugs

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Drying Drop Technology as a Possible Tool for Detection Leukemia and Tuberculosis in Cattle

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Journal of Biomedical Science and Engineering 2015年第1期8卷 1-23页

作者： Tatiana A. Yakhno Anatoly A. Sanin Robert G. Ilyazov Gulusa v. vildanova Rafat A. Khamzin Nadezhda P. Astascheva Mikhail G. Markovsky vadim D. Bashirov vladimir G. Yakhno Department of Radiophysical Methods in Medicine Institute of Applied Physics Russian Academy of Sciences (IAP RAS) Nizhny Novgorod Russia Department of Agricultural Sciences Academy of Sciences of the Republic of Tatarstan (AS RT) Kazan Russia Department of Biotechnology and Standardization Bauman Kazan State Academy of Veterinary Medicine (KSAVM) Kazan Russia Department of Technique and Technology Financial Technological Academy (FTA) Moscow Region Korolyev Russia Department of Trial Wine-Making North-Caucasian Zonal Research Institute of Horticulture and Viticulture of the Russian Academy of Agricultural Sciences (NCZRIH & V) Krasnodar Russia Department of Food Biotechnology Orenburg State University (OSU) Orenburg Russia

Usual response of organism to viral or bacterial invasion represents antibodies production, qualitative and quantitative changes in composition of biological fluids. These changes influence conformation and surface characteristics of macromolecules (proteins), which become apparent in sessile drying drops, when they form aggregates due to salting-out effect and sediment. The bottom adsorption layers change their adhesive and viscoelastic properties in time depending on fluid composition and structure. The aim of this study was verification the idea of using this phenomenon in rapid vet diagnostics. Milk, blood and serum samples of 183 cows were tested using Drop Drying Technology (DDT). A drop of tested fluid dried on a polished quartz plate, oscillated with constant frequency—60 kHz. Mechanical properties of the drop changed during drying, influenced the electrical conductivity of the quartz plate. This signal was converted to the Acoustical- Mechanical Impedance (AMI) and displayed as a curve in coordinates AMI vs. Time. Shape of the AMI curve reflected this dynamics, and was used as a target for quantitative comparison between control and infected animals. Frequency analysis of the estimated parameters of the curves was performed using features of the Excel program. Powerful method of artificial neural network processing of the experimental data was also tested in this work as a possible tool for future development. Significant differences between control, Bovine leucosis virus positive (BLv+) and Bovine tuberculin positive (BTub+) cattle groups were obtained using all biological fluids—blood, serum and milk. We fixed also a season shift of the data, but distinction between groups still remained. In serum and milk some features of the AMI curves were more stable, and retained diagnostic properties when combined winter and spring databases. Further development of DDT is proposed.

关键词： Sessile Drying Drops Biological Fluids Dynamics of Mechanical Properties Acoustical Impedancemetry vet Diagnostics

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复发缓解型多发性硬化与人类疱疹病毒6型活动性感染

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世界核心医学期刊文摘（神经病学分册） 2005年第3期1卷 10-11页

作者： lvarez Lafuente R. De Las Heras v. BartoloméM. 黄卫东 Lab.de Invest.Ta Norte Hospital Clnico San Carlos C/ Profesor Martn Lagos s/n 28040 Madrid Spain Dr.

Background: Recent studies have focused on the relationship between human herp esvirus 6 (HHv 6) and multiple sclerosis (MS). Objective: To analyze HHv 6 mes senger RNA expression in patients with relapsing remitting (RR) MS vs healthy b lood donors (HBDs). Design: One hunred fiftyfour subjects were enrolled in the study: 105 patients with [Dr. R. Alvar ez Lafuente, Lab. de Invest. 7a Norte, Hospi RRMS (32 in relapse) and 49 HBDs. Total DNA and messenger RNA were extracted from serum and blood samples, respec tively, and analyzed by quantitative real time reverse transcription polymeras e chain reaction for the detection of 3 HHv 6 immediate early genes (U16/U17, U89/U90, and U94) and both HHv 6 variants (HHv 6A and HHv 6B). Results: Activ e HHv 6 infection was detected in 16%of patients with RRMS vs 0%of HBDs (P=.0 03). Seven patients with RRMS with exacerbation had HHv 6 active replication, a nd the virus remained latent in only 1 of them. We did not find any statisticall y significant difference between HHv 6 active or latent infection for patients in remission (P = .12). Among patients with RRMS with HHv 6 active replication, viral load was higher when they experienced an acute attack than when in remiss ion (P = .04). In those patients with RRMS who had an active infection only, HHv 6A was found. Cell free HHv 6 DNA detected in serum samples confirmed the re sults. Conclusions: The results show that a subset of patients with RRMS experie nce HHv 6 active infection, and there likely is an association between the vira l active replication and relapses; therefore, HHv 6 active infection may imply a greater risk of exacerbations in a subgroup of patients with RRMS.

关键词：人类疱疹病毒活动性感染多发性硬化健康献血者即刻早期基因全血标本潜伏性感染缓解期患者病毒量受试对象

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流行性出血热病毒核酸的提取

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病毒学报 1987年第2期 120-124页

作者：杭长寿,Kiley M.P,Lange J.v,Macormick J.B,宋干中国预防医学科学院囊毒学研究所美国疾病控制中心特殊病原室美国疾病控制中心特殊病原室美国疾病控制中心特殊病原室中国预防医学科学院病毒学研究所北京亚特兰大亚特兰大亚特兰大北京

本文报告流行性出血热R22和A9株病毒培养,同位素标记及核酸提取的初步研究,並获得了该病毒核酸的3个片段即L、M、S、分子量分别约为:3.8、1.9和0.86×10～5道尔顿,不论用20～70％蔗糖密度梯度离心提纯的病毒,或用30％蔗糖垫层离心的粗... 详细信息

本文报告流行性出血热R22和A9株病毒培养,同位素标记及核酸提取的初步研究,並获得了该病毒核酸的3个片段即L、M、S、分子量分别约为:3.8、1.9和0.86×10～5道尔顿,不论用20～70％蔗糖密度梯度离心提纯的病毒,或用30％蔗糖垫层离心的粗制病毒,均获同样结果,但多数情况下,用蔗糖密度梯度离心时,除病毒峰外,还发现主要由细胞组份(即线粒体和核糖体等)组成的另一峰,并经常影响病毒RNA的提取,对如何获得纯净病毒及其核酸进行了讨论。

关键词：流行性出血热病毒 RNA

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多西紫杉醇治疗用蒽环类抗生素预治疗的AIDS相关Kaposi肉瘤:回顾性研究

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世界核心医学期刊文摘（皮肤病学分册） 2005年第9期1卷 6-7页

作者： Autier J. Picard-Dahan C. Marinho E. v. Descamps 张宪旗 Department of Dermatology Bichat Claude Bernard Hospital Assitance Publique-H.opitaux de Paris 46 rue Henri Huchard 75018 Paris France Prof.

Background:Kaposi’s sarcoma (KS) is a potentially life-threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome(AIDS)related KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization. Objectives:We studied the efficacy and tolerance of docetaxel in the treatment of AIDS-related KS after pretreatment with anthracycline. Patients/methods and main outcome measure:A retrospective cohort study was done. Nine human immunodeficiency virus (HIv)-infected patients were treated from 1997 to 2002 with docetaxel. Tumour response was evaluated using the AIDS Clinical Trial Group (ACTG) staging criteria. Clinical and biological toxicity was evaluated. AIDS status with HIv viral load and CD4T-cell count were measured at the beginning and at the end of the treatment. Results:A major (complete or partial)response and a stabilization of the disease were demonstrated in seven and two patients, respectively. Grade 4 neutropenia and thrombocytopenia were observed in four of nine and one of nine patients, respectively. One patient died after sepsis. Conclusions:Docetaxel has a good and rapid efficacy in anthracycline-pretreated patients with severe AIDS-related KS. Phase II/III trials should be done to compare docetaxel with liposomal anthracyclines as a first-line treatment.

关键词：预治疗蒽环类抗生素 Kaposi 联合化疗白细胞减少症抗病毒疗法 Ⅲ期临床试验多中心性免疫功能细胞计数

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聚乙二醇干扰素α-2b和(或)拉米夫定治疗慢性乙型肝炎或HBeAg阴性患者病毒动力学研究

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世界核心医学期刊文摘（胃肠病学分册） 2005年第10期1卷 40-41页

作者： Sypsa v.-A. Mimidis K. Tassopoulos N.C. A. Hatzakis 王志宇 Department of Hygiene and Epidemiology Athens University Medical School 75 Mikras Asias Street 15 27 Athens Greece Dr.

We studied viral dynamic parameters in 44 chronic hepatitis B/hepatitis B e antigen (HBeAg)(-) patients treated with pegylated interferon alfa-2b (PEG-IFN) 100 or 200 μg weekly or lamivudine 100 mg daily or the combination of PEG-IFN 100 or 200 μg with lamivudine. Patients receiving PEG-IFN monotherapy exhibited viral load oscillations between weekly injections, which were resolved by the addition of lamivudine. The median pharmacological delay was estimated at 4.1, 5.8, and 1.8 hours in PEG-IFN monotherapy, PEG-IFN 100/200 μg +lamivudine, and lamivudine monotherapy, respectively (P = .44). The median half-life of free virus was 12.7 hours (range, 2.4-69.2 hours). The mean antiviral effectiveness of PEG-IFN 100/200 μg monotherapy was lower than that of lamivudine (82.6%vs. 96.4%; P = .005). The mean effectiveness of PEGIFN 100 μg +lamivudine and PEG-IFN 200 μg +lamivudine was 92.8%and 94.4%, respectively. The half-life of infected cells ranged from 2.7 to 75 days. The median half-life of infected cells in patients receiving the combination regimens of PEG-IFN and lamivudine was similar to that of lamivudine patients (5.0 days vs. 6.0 days, P = .77). In conclusion, the addition of pegylated interferon alfa-2b in lamivudine treatment was found to neither enhance the potency of blocking HBv production nor the decay rates of infected cells.

关键词： HBeAg阴性干扰素α 乙型肝炎阴性患者复制能力感染细胞平均有效率负荷波动

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Squamous Cell Carcinoma over Cutaneous verrucous Lichen: One Case in Parakou (Benin)

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Journal of Cosmetics, Dermatological Sciences and Applications 2019年第4期9卷 284-291页

作者： Christiane Koudoukpo L. v. C. Brun F. Akpadjan B. Dégboé N. Agbessi E. Mensah M. C. Ballé F. Malaté H. Adégbidi F. Atadokpèdé CHU Borgou/Alibori Parakou Benin CNHU Hubert Koutoukou Maga Cotonou Benin

Introduction: We report an unusual case of squamous cell carcinoma on a verrucous lichen of chronic evolution taken in charge in Borgou/Alibori UHC in Parakou (Bénin). Observation: A 75-year old Beninese woman with a history of portal hypertension post-viral cirrhosis C treated with negative viral load, had consulted for a large chronic ulceration of the right foot back. The beginning of the symptomatology would go back to about 30 years, marked by lichenified, pruriginous popular lesions;these lesions would initially be treated as eczema and then mycosis by health personnel not specialised in dermatology and multitreated with unspecified topicals. General state was altered. In addition to ulceration, the dermatological examination found plates of hyperpigmented lichen lesion, homogeneous and well limited bilateral and symmetrical topography on the pelvic limbs making difficult to walk. Anatomopathological examination of the biopsy sample straddling the ulceration and its edges suggested a hypertrophic cutaneous lichen associated with keratinizing, infiltrating epidermal carcinoma. The chest-abdominal-pelvic scan showed no metastasis. A complete amputation of the right leg and knee was performed after a psychological interview. The follow-up was marked by an over-infection of the amputation stump by Escherichia coli, which was successfully treated. Healed, she is waiting for orthopedic equipment and possible chemotherapy. Conclusion: This clinical case indicates the need for adequate management of certain potentially precancerous dermatoses, in order to limit the progression to carcinogenic transformation.

关键词： Cutaneous verrucous Lichen Squamous Cell Carcinoma Amputation Parakou

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Novel PF74-like small molecules targeting the HIv-1 capsid protein:Balance of potency and metabolic stability

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Acta Pharmaceutica Sinica B 2021年第3期11卷 810-822页

作者： Lei Wang Mary CCasey Sanjeev Kumar vvernekar Rajkumar Lalji Sahani Karen AKirby Haijuan Du Huanchun Zhang Philip RTedbury Jiashu Xie Stefan GSarafianos Zhengqiang Wang Center for Drug Design College of PharmacyUniversity of MinnesotaMN 55455USA Department of Pharmaceutical Sciences School of Chemical EngineeringDalian University of TechnologyDalian 116024China Department of Molecular Microbiology and Immunology University of Missouri School of MedicineChristopher S.Bond Life Sciences CenterColumbiaMO 65211USA Laboratory of Biochemical Pharmacology Department of PediatricsEmory University School of MedicineAtlantaGA 30322USA

Of all known small molecules targeting human immunodeficiency virus(HIv)capsid protein(CA),PF74 represents by far the best characterized chemotype,due to its ability to confer antiviral phenotypes in both early and late phases of viral ***,the prohibitively low metabolic stability renders PF74 a poor antiviral *** report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding ***,we replaced the inter-domain-interacting,electron-rich indole ring of PF74 with less electron-rich isosteres,including imidazolidine-2,4-dione,pyrimidine-2,4-dione,and benzamide,and identified four potent antiviral compounds(10,19,20 and 26)with markedly improved metabolic *** to PF74,analog 20 exhibited similar submicromolar potency,and much longer(51-fold)half-life in human liver microsomes(HLMs).Molecular docking corroborated that 20 binds to the PF74 binding site,and revealed distinct binding interactions conferred by the benzamide ***,our data support compound 20 as a promising antiviral lead.

关键词： HIv-1 Capsid protein PF74 Microsomal stability

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