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1.
J Virol ; 86(22): 12053-68, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22933280

ABSTRACT

Productive replication of human immunodeficiency virus type 1 (HIV-1) occurs efficiently only in humans. The posttranscriptional stages of the HIV-1 life cycle proceed poorly in mouse cells, with a resulting defect in viral assembly and release. Previous work has shown that the presence of human chromosome 2 increases HIV-1 production in mouse cells. Recent studies have shown that human chromosome region maintenance 1 (hCRM1) stimulates Gag release from rodent cells. Here we report that expressions of hCRM1 in murine cells resulted in marked increases in the production of infectious HIV-1 and feline immunodeficiency virus (FIV). HIV-1 production was also increased by hSRp40, and a combination of hCRM1 and hSRp40 resulted in a more-than-additive effect on HIV-1 release. In contrast, the overexpression of mouse CRM1 (mCRM1) minimally affected HIV-1 and FIV production and did not antagonize hCRM1. In the presence of hCRM1 there were large increases in the amounts of released capsid, which paralleled the increases in the infectious titers. Consistent with this finding, the ratios of unspliced to spliced HIV-1 mRNAs in mouse cells expressing hCRM1 and SRp40 became similar to those of human cells. Furthermore, imaging of intron-containing FIV RNA showed that hCRM1 increased RNA export to the cytoplasm.By testing chimeras between mCRM1 and hCRM1 and comparing those sequences to feline CRM1, we mapped the functional domain to HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats 4A to 9A and a triple point mutant in repeat 9A, which showed a loss of function. Structural analysis suggested that this region of hCRM1 may serve as a binding site for viral or cellular factors to facilitate lentiviral RNA nuclear export.


Subject(s)
HIV Infections/metabolism , HIV/metabolism , Immunodeficiency Virus, Feline/metabolism , Karyopherins/physiology , Lentivirus Infections/metabolism , Receptors, Cytoplasmic and Nuclear/physiology , Active Transport, Cell Nucleus , Alleles , Animals , Cell Cycle Proteins/metabolism , Cytoplasm/metabolism , HeLa Cells , Humans , Introns , Karyopherins/metabolism , Mice , Molecular Conformation , Plasmids/metabolism , RNA, Viral/metabolism , RNA-Binding Proteins/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Repressor Proteins/metabolism , Serine-Arginine Splicing Factors , Transfection , Exportin 1 Protein
2.
Postepy Hig Med Dosw (Online) ; 66: 339-47, 2012 Jun 14.
Article in English | MEDLINE | ID: mdl-22706120

ABSTRACT

INTRODUCTION: Hepatitis C virus (HCV) infection in Poland affects approximately 750 thousand persons. The prevention of cirrhosis and hepatocellular carcinoma, of which approximately 20% of patients with chronic hepatitis C virus are at risk, aims at eradication of the virus by applying antiviral treatment with pegylated interferon alpha with ribavirin. MATERIAL/METHODS: In this paper the results of the standard treatment of chronic hepatitis C in a population of 169 adult patients in whom it was started in the period of 01.01.2007-30.06.2008 are analyzed. Moreover, the influence of various clinical, biochemical and viral factors on achieving therapeutic success in the form of the sustained virological response (SVR) was studied. RESULTS: In the group of 128 patients who received the full course of antiviral treatment, the SVR was achieved by 67.2% of patients (86 persons), whereas regarding all 169 patients who started the therapy, the sustained disappearance of viremia was found in 53.2% of patients (90 persons). Regarding 155 persons in whom the treatment was not interrupted for reasons others than virology, this value was 55.5%. For the sustained disappearance of viremia the following was favorable: genotype 3 virus, age under 40 years, body mass up to 75 kg, correct value of body mass index (BMI), low gamma-glutamyl transpeptidase (GGTP) activity before the treatment, minimum advancement of liver fibrosis in a liver biopsy (S1), complete early biochemical response (cEBR), and moreover, the achievement of negation of viremia after 12 weeks of the treatment in a group of patients infected with genotype 1 (complete early virological response, cEVR). These factors were strongly correlated with each other and that is why an analysis by the method of logistic multiple regression was impossible. Adverse reactions to the treatment and other health problems were the reasons for earlier discontinuation of the standard therapeutic scheme in 14 patients, whereby the lack of an SVR occurred in 10 of them (71.5% which is 5.9% of the studied population).


Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Viremia/drug therapy , Adolescent , Adult , Age Factors , Aged , Alanine Transaminase/metabolism , Biopsy , Drug Therapy, Combination , Female , Hepatitis C, Chronic/enzymology , Hepatitis C, Chronic/pathology , Humans , Liver/enzymology , Liver/pathology , Male , Middle Aged , Recombinant Proteins/administration & dosage , Treatment Outcome , Viremia/complications , Young Adult
3.
Ann Agric Environ Med ; 19(4): 738-41, 2012.
Article in English | MEDLINE | ID: mdl-23311799

ABSTRACT

INTRODUCTION AND OBJECTIVE: Based on the available epidemiologic data, Poland currently has the features typical for areas of very low endemicity for hepatitis A. The incidence of hepatitis A in the Wielkopolska region in years 2006-2008 was 0.68/100,000 inhabitants or significantly lower. The aim of this cross-sectional analysis was to evaluate the seroprevalence of anti-HAV antibodies in inhabitants of the Wielkopolska region of western Poland regarding some demographic factors. MATERIAL AND METHODS: In addition to testing anti-HAV antibodies, the medical history and demographic data, such as age, gender, place of residence, and level of education of 680 patients and 105 healthy blood donors were analyzed. RESULTS: Anti-HAV antibodies were observed in 235 cases (29.9%). In univariate regression analysis, the covariates correlated with positive anti-HAV testing were age, female gender and lower level of education. Only 6.2% of young adults were seropositive. Among study participants above the age of 50, anti-HAV antibodies were present in 64-100% of cases. An icteric disease consistent with hepatitis A diagnosis was identified in the histories of 10.2% of seropositive patients. CONCLUSIONS: The risk for contracting disease after exposure to HAV in young (<40 years old) inhabitants of the Wielkopolska region is high. Apart from older individuals, also women and people with a lower level of education are more frequently seropositive. A low level of immunity to HAV should be an indication for vaccination against HAV , especially in selected groups.


Subject(s)
Hepatitis A virus/isolation & purification , Hepatitis A/epidemiology , Adolescent , Adult , Aged , Cross-Sectional Studies , Demography , Female , Hepatitis A Antibodies/blood , Humans , Immunoenzyme Techniques , Male , Middle Aged , Poland/epidemiology , Prevalence , Risk Factors , Seroepidemiologic Studies , Socioeconomic Factors , Young Adult
4.
Przegl Epidemiol ; 60(1): 7-15, 2006.
Article in Polish | MEDLINE | ID: mdl-16758733

ABSTRACT

OBJECTIVE: Evaluation the value of procalcitonin as a diagnostic and prognostic marker in septic patients and patients with systemic inflammatory response syndrome (SIRS). MATERIAL AND METHODS: 126 patients were included into the study. The patients were divided into four groups: 1--septic patients with positive blood cultures, 2--septic patients with negative blood cultures, 3--patients with SIRS, 4--patients without sepsis and SIRS. PCT level was measured by imunoluminometric assay (LUMItest) and immunochromatographic assay (PCT-Q). RESULTS: PCT level is higher in patients with sepsis than in patients with SIRS. PCT level is only slightly elevated in patients without sepsis and SIRS. The highest PCT level is found in patients with septic shock. In patients with the clinical improvement the frequency of PCT level increase is approximately twice lower than in patients who died. CONCLUSIONS: Measurement of PCT level on the first, second and third day of hospitalization has no prognostic value. There is no significant difference in PCT level in sepsis caused by Gram positive and Gram negative bacteria. PCT is a useful marker in diagnosis of sepsis but its role in monitoring the severity of sepsis requires more clinical studies.


Subject(s)
Calcitonin/blood , Protein Precursors/blood , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Calcitonin Gene-Related Peptide , Chromatography/methods , Female , Humans , Immunoassay/methods , Male , Middle Aged , Sepsis/blood , Sepsis/diagnosis , Severity of Illness Index , Systemic Inflammatory Response Syndrome/metabolism
5.
Przegl Epidemiol ; 58(4): 583-7, 2004.
Article in Polish | MEDLINE | ID: mdl-15810499

ABSTRACT

A case of chicken-pox complicated by hepatitis and endocarditis in 21 years old man was described. Three weeks before admission to the Department of Infectious Diseases the patient stayed at the Neurological Department and was diagnosed as encephalitis. The spots on the skin and a very high level of aminotransferases were noticed in 19th day of hospitalization. The blood cultures were positive for Staphylococcus aureus MSSA. Bacterial endocarditis was diagnosed on the base of echocardiography. The patient was treated with antibiotics six weeks. He recovered completely.


Subject(s)
Chickenpox/complications , Endocarditis, Bacterial/complications , Hepatitis, Viral, Human/complications , Adult , Anti-Bacterial Agents/administration & dosage , Antiviral Agents/administration & dosage , Chickenpox/drug therapy , Chickenpox/physiopathology , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Hepatitis, Viral, Human/drug therapy , Humans , Male , Poland , Staphylococcus aureus/isolation & purification , Time Factors , Treatment Outcome
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