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Positional effect of mutations in 5'UTR of hepatitis C virus 4a on patients' response to therapy

World Journal of Gastroenterology 2009年第12期15卷 1480-1486页

作者： Mostafa K El Awady Hassan M Azzazy Ahmed M Fahmy Sherif M Shawky Noha G Badreldin Samar S Yossef Moataza H Omran Abdel Rahman N Zekri said a goueli Department of Biomedical Technology National Research CenterDokkiCairo 12622Egypt Department of Chemistry and Yousef Jameel Science and Technology Research Center the American University in CairoCairo 11511Egypt Structural biology department Free University of AmsterdamDe Boelelaan 10851081 HV AmsterdamThe Netherlands National Cancer Institute Cairo 11796Egypt Department of Pathology and Laboratory Medicine University of WisconsinMadisonWI 53711United States

AIM： To investigate the effects of mutations in domain Ⅲ of the hepatitis C virus （HCV） internal ribosome entry sequences （IRES） on the response of chronic HCV genotype 4a patients to interferon therapy.METHODS： HCV RNA was extracted from 19 chronic HCV 4a patients receiving interferon/ribavirin therapy who showed dramatic differences in their response to combination therapy after initial viral clearance. IRES domain Ⅲ was cloned and 15 clones for each patient were sequenced. The obtained sequences were aligned with genotype 4a prototype using the ClustaIW program and mutations scored. Prediction of stem-loop secondary structure and thermodynamic stability of the major quasispecies in each patient was performed using the MFOLD 3.2 program with Turner energies and selected constraints on base pairing.RESULTS： Analysis of RNA secondary structure revealed that insertions in domain Ⅲ altered WatsonCrick base pairing of stems and reduced molecular stability of RNA, which may ultimately reduce binding affinity to ribosomal proteins. Insertion mutations in domain - were statistically more prevalent in sustained viral response patients （SVR, n = 14） as compared to breakthrough （BT, n = 5） patients.CONCLUSION： The influence of mutations within domain Ⅲ on the response of HCV patients to combination therapy depends primarily on the position, but not the frequency, of these mutations within IRES domain Ⅲ.

关键词： Hepatitis C virus Internal ribosome entrysequences Domain Ⅲ Genotype 4a Ribosomal sub-unit Interferon therapy RNA folding

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HepG2 cells support viral replication and gene expression of hepatitis C virus genotype 4 in vitro

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World Journal of Gastroenterology 2006年第30期12卷 4836-4842页

作者： Mostafa K El-Awady Ashraf A Tabll Yasmine S El-Abd Mahmoud M Bahgat Hussein A Shoeb Samar S Youssef Noha G Bader El Din El-Rashdy M Redwan Maha El-Demellawy Moataza H Omran Wael T El-Garf said a goueli Department of Biomedical Technology National Research Center Tahrir Street PO 12622 Dokki Cairo Egypt Department of Medicinal Chemistry Na- tional Research Center Tahrir Street PO 12622 Dokki Cairo Egypt Department of Microbiology and Immunology Faculty of Pharmacy Cairo University Cairo Egypt Genetic Engineering and Biotechnology Research Institute New Borg El-Arab City Alexandria Egypt Department of Pathology School of Medicine University of Wisconsin Madison WI United States

AIM： TO establish a cell culture system with longterm replication of hepatitis C virus （HCV） genome and expression of viral antigens in vitro. METHODS： HepG2 cell line was tested for its susceptibility to HCV by incubation with a serum from a patient with chronic hepatitis C. Cells and supernatant were harvested at various time points during the culture. Culture supernatant was tested for its ability to infect na＇ive cells. The presence of minus （antisense） RNA strand, and the detection of core and E1 antigens in cells were examined by RT-PCR and immunological techniques （flow cytometry and Western blot） respectively. RESULTS： The intracellular HCV RNA was first detected on d 3 after infection and then could be consistently detected in both cells and supernatant over a period of at least three months. The fresh cells could be infected with supernatant from cultured infected cells. Flow cytometric analysis showed surface and intracellular HCV antigen expression using in house made polyclonal antibodies （anti-core, and anti-E1）. Western blot analysis showed the expression of a cluster of immunogenic peptides at molecular weights extended between 31 and 45 kDa in an one month old culture of infected cells whereas this cluster was undetectable in uninfected HepG2 cells. CONCLUSION： HepG2 cell line is not only susceptible to HCV infection but also supports its replication in vitro. Expression of HCV structural proteins can be detected in infected HepG2 cells. These cells are also capable of shedding viral particles into culture media which in turn become infectious to uninfected cells.

关键词： Hepatitis C virus In vitro propagation Genomic replication Gene expression HepG2 cells

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The role of photovaporization of the prostate in small volume benign prostatic hyperplasia and review of the literature

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Asian Journal of Urology 2019年第4期6卷 353-358页

作者： Dominique Thomas Kevin C.Zorn Malek Meskawi Ramy goueli Pierre-Alain Hueber Lesa Deonarine Vincent Misrai Alexis Te Bilal Chughtai Department of Urology Weill Cornell Medical College/New York PresbyterianNew YorkNYUSA Section of Urology Department of SurgeryUniversity of Montreal Hospital CenterMontrealQCCanada

Objective:Our objective was to characterize the safety and efficacy of the 180 W XPS-GreenLight laser in men with lower urinary tract symptoms secondary to a small volume benign prostatic hyperplasia(BPH).Methods:A retrospective analysis was performed for all patients who underwent 180 W XPSlaser photoselective vaporization of the prostate(PVP)vaporization of the prostate between 2012 and 2016 at two-tertiary medical *** collection included baseline comorbidities,disease-specific quality of life scores,maximum urinary flow rate(Qmax),postvoid residual(PVR),complications,prostate volume and prostate-specific antigen(PSA).The secondary endpoints were the incidence of intraoperative and postoperative adverse *** were stratified using the Clavien-Dindo grading system up to 90 days after ***:Mean age of men was 67.8 years old,with a mean body mass index of 29.7 kg/*** prostate volume as measured by transrectal ultrasound was 29 *** use was 47%and urinary retention with catheter at time of surgery was 17%.Mean hospital stay and catheter time were 0.5 *** follow-up time was 6 months with the longest duration of follow-up being 22.5 months(interquartile range,3-22.5 months).The International Prostate Symptom Score improved from 22.8±7.0 at baseline to 10.7±7.4(p<0.01)and 6.3±4.4(p<0.01)at 1 and 6 months,*** Qmax improved from 7.70±4.46 mL/s at baseline to 17.25±9.30 mL/s(p<0.01)and 19.14±7.19 mL/s(p<0.001)at 1 and 6 months,respectively,while the PVR improved from 216.0±271.0 mL preoperatively to 32.8±45.3 mL(p<0.01)and 26.2±46.0 mL(p<0.01)at 1 and 6 months,*** PSA dropped from 1.97±1.76 ng/mL preoperatively to 0.71±0.61 ng/mL(p<0.01)and 0.74±0.63 ng/mL at 1 and 6 months,*** patient had a bladder neck contracture postoperatively and no capsular perforations were noted ***:The 180 W GreenLight XPS system is safe and effective for men with small volume

关键词： Benign prostatic hyperplasia Photovaporization of the prostate GreenLight XPS Lower urinary tract symptoms Small prostate

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