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1.
Artigo em Inglês | MEDLINE | ID: mdl-36439049

RESUMO

Background: Uganda's population, though, largely characterized by young people, has seen the number of people aged 60 and over grow from 686,000 twenty years ago, to 1,433,596 in 2014. Effective caring for the well-being of this population requires strategic and deliberate planning that involves Quality Of Life (QoL) assessments. QoL assessments among the elderly are important in evaluating the efficacy of strategies, such as health interventions, welfare programs, health care and well-being of the elderly. However, elderly in Uganda face several challenges, ranging from loneliness, poor housing, lack of social and financial support and poor health. These may negatively affect older persons' quality of life and consequently their perceptions and attitudes towards aging. Methods: The study was carried out in 2019 in the communities of Nansana and Busukuma town councils in Wakiso district, Uganda. The participants were 380 people 60 years and older. To establish the association between perceptions of ageing and QoL, this study utilized a locally adapted version of the Older Person's Quality of Life Questionnaire (OPQOL) and the Brief Ageing Perceptions Questionnaire (B-APQ). The OPQOL assesses three domains of QoL: Health QoL (HQoL); Social economic QoL (SQoL); and Psychosocial QoL (PQoL). The B-APQ assesses perceptions about physical age, participation in social activities, and perceptions about ability to regulate emotions as one ages. Pearson's Chi-square tests were used to characterize the relationship between the perceptions and quality of life. Results: The majority of the respondents, 61% (95%CI 56.7-64.8), had negative perceptions towards ageing. Eighty six percent had poor HQoL, 90% poor SQoL and 83% poor PQoL. There was a significant association between good HQoL and positive perception about participation in social activities (X2 = 7.3670, P = 0.007) as well as with positive perception on regulation of emotions (X2 = 18.1803, P<0.001). There was a significant association between good SQoL and positive perception about participation in social activities (X2 = 5.3472, P = 0.021), as well with positive perception on regulation of emotions (X2 = 10.5128, P<0.001). A significant association between good PQoL and positive perception on regulation of emotions (X2 = 9.2414, P= 0.002). Conclusion: Positive perceptions of ageing are associated with good QoL. Directly addressing perceptions of ageing could be a low cost and effective strategy to improve the QoL of older persons in SSA.

2.
Virusdisease ; 30(4): 490-497, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31897414

RESUMO

The availability of generic direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has prompted many low-and-middle-income countries to launch HCV elimination programs. Because the efficacy of some of these generic DAAs varies by HCV viral subtype, information on subtype distribution can contribute important information to these elimination programs. We conducted a cross-sectional serosurvey to characterize HCV subtype diversity among HIV positive people who inject drugs (PWID) across 14 cities in India. Of 801 HIV positive PWID sampled, 639 tested HCV antibody positive (78.9%). Among 105 samples sequenced, genotype 3 (58.1%) was the most commonly observed followed by genotype 1 (36.2%) and genotype 6 (5.7%). Of the genotype 3 infections, 65% were subtype 3a and 35% were subtype 3b. Of the genotype 1 infections, 94% were subtype 1a and 6% were subtype 1b. All genotype 6 samples were subtype 6n. There was some variability in genotype diversity depending on geographic region and PWID epidemic stage with greater diversity observed in older PWID epidemics. One sequence, HY018, did not cluster with any known reference sequences in phylogenetic analysis. Nearly 80% of HIV infected PWID across India are co-infected with HCV, and subtype prevalence and genetic diversity varied by region and PWID epidemic stage. HCV elimination programs in India will need to consider HCV subtype.

3.
Sci Rep ; 8(1): 7758, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29773822

RESUMO

Various synchrotron radiation-based spectroscopic and microscopic techniques are used to elucidate the room-temperature ferromagnetism of carbon-doped ZnO-nanowires (ZnO-C:NW) via a mild C+ ion implantation method. The photoluminescence and magnetic hysteresis loops reveal that the implantation of C reduces the number of intrinsic surface defects and increases the saturated magnetization of ZnO-NW. The interstitial implanted C ions constitute the majority of defects in ZnO-C:NW as confirmed by the X-ray absorption spectroscopic studies. The X-ray magnetic circular dichroism spectra of O and C K-edge respectively indicate there is a reduction in the number of unpaired/dangling O 2p bonds in the surface region of ZnO-C:NW and the C 2p-derived states of the implanted C ions strongly affect the net spin polarization in the surface and bulk regions of ZnO-C:NW. Furthermore, these findings corroborate well with the first-principles calculations of C-implanted ZnO in surface and bulk regions, which highlight the stability of implanted C for the suppression and enhancement of the ferromagnetism of the ZnO-C:NW in the surface region and bulk phase, respectively.

4.
J Nanosci Nanotechnol ; 11(9): 8269-73, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22097567

RESUMO

In this work, we have synthesized multiwall nitrogenated carbon nanotubes (MW-NCNTs) with Fe-catalysts by the microwave plasma-enhanced chemical vapor deposition process @950 degrees C and subsequently functionalized with chlorine and oxygen. The dia-magnetic behavioral M-H loop of non-functionalized MW-NCNTs were turn into ferromagnetic behaviors by the process of chlorination and oxidation respectively; which were characterized by means of superconducting quantum interference device magnetometer within the temperature range 5-300 K. A prominent cusp like behavior is also observed at around approximately 45 K in M(FC) and M(ZFC) measurements confirming the ferromagnetic behaviors of these MW-NCNTs after chlorination and oxidation.

6.
Nanoscale ; 2(12): 2777-82, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20936206

RESUMO

Water soluble graphene with various chemical- and biofunctionalities is essential for their different applications. However, exfoliated graphenes are insoluble in water and water soluble graphene oxide precipitate if they are chemically reduced to graphene. We have developed a polyacrylate coating method for graphene oxide and then chemically reduced it into graphene. We found that polyacrylate coating can improve the colloidal stability of both graphene and graphene oxide. The coated graphene has been characterized using XPS, FTIR, XRD and micro-Raman spectroscopy. The primary amine present on the coating backbone has been used to derive glucose functionalized water soluble graphene. Various other functional graphenes can be anticipated from the polyacrylate coated graphene.


Assuntos
Resinas Acrílicas/química , Grafite/química , Óxidos/química , Glucose/química , Concentração de Íons de Hidrogênio , Espectroscopia Fotoeletrônica , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
7.
J Phys Condens Matter ; 20(46): 465105, 2008 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-21693839

RESUMO

Fe and Y K-edge extended x-ray absorption fine structure, Fe(Y) L(3,2)-edge (L(3)-edge) x-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VB-PES) measurements have been carried out to study soft magnetic ternary Fe(78-x)Y(x)B(22) bulk metallic glasses (BMGs). The combined XANES and VB-PES results do not show broadening of the Fe 3d band to support the previous interpretation of the reduction of the magnetic moment in BMGs by Y-induced decrease of exchange splitting of Fe 3d orbitals. Instead, the density of delocalized/itinerant Fe 3d states in the vicinity of the Fermi level is found to be reduced by Y substitution, which reduces the strength of itinerant-states-mediated ferromagnetic coupling between local spins on the Fe ions and the total magnetic moment of the Fe-based BMGs.

8.
J Phys Condens Matter ; 19(17): 176204, 2007 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-21690950

RESUMO

X-ray absorption near-edge structure (XANES) and valence-band photoemission spectroscopy (VB-PES) were used to elucidate the electronic and mechanical properties of diamond-like carbon (DLC) thin films deposited by the plasma-enhanced chemical vapour deposition method at various bias voltages (V(b)) using a C(2)H(2) vapour precursor in an Ar(+) atmosphere. The increase of V(b) is found to increase and decrease the contents of sp(3)- and sp(2)-bonded carbon atoms, respectively, i.e. the films become more diamond-like. The Young's modulus measurements show increases with the increase of the presence of sp(3)-bonded carbon atoms in the structure of the DLC films.

9.
J Biomed Mater Res B Appl Biomater ; 78(2): 222-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16544310

RESUMO

This article reports results of endothelial cell interaction with atom beam source N-doped a-C:H (diamond-like carbon, DLC) as it compares with that of Si-doped DLC thin films. The RF plasma source exhibits up to 40% N-dissociation and N-atomic fluxes of approximately 0.85 x 10(18) atoms/s, which ensures better atomic nitrogen incorporation. Two different types of nitrogen species (with and without the use of sweep plates to remove charged ions) were employed for nitrogen doping. The number of attached endothelial cells is highest on Si-DLC, followed by the N-DLC (where the sweep plates were used to remove ions), the N-DLC (without the use of sweep plates), undoped DLC, and finally the uncoated sample. The contact angle values for these films suggest that water contact angle is higher in the atomic nitrogen neutral films and Si-DLC films compared to the ionized-nitrogen specie doped films and undoped DLC thin films, suggesting that the more hydrophobic films, semiconducting films, and film with relieved stress have better interaction with human microvascular endothelial cells. It seems evident that N-doping increases the Raman I(D)/I(G) ratios, whereas N-neutral doping decreases it slightly and Si-doping decreases it even further. In this study, lower Raman I(D)/I(G) ratios are associated with increased sp(3)/sp(2) ratio, an increased H concentration, photoluminescence intensity, and a higher endothelial cellular adhesion. These investigations could be relevant to biocompatibility assessment of nanostructured biomaterials and tissue engineering.


Assuntos
Materiais Revestidos Biocompatíveis , Diamante , Células Endoteliais , Teste de Materiais , Silício , Adesão Celular , Células Cultivadas , Diamante/química , Células Endoteliais/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura , Nanoestruturas , Nanotecnologia , Nitrogênio/química , Silício/química , Propriedades de Superfície , Engenharia Tecidual
11.
J Exp Med ; 194(10): 1395-406, 2001 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-11714747

RESUMO

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1-2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-gamma- CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38- and started producing IFN-gamma in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host-virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+ T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.


Assuntos
Hepatite C/imunologia , Doença Aguda , Adulto , Alanina Transaminase/sangue , Linfócitos T CD4-Positivos/imunologia , Feminino , Hepatite C/virologia , Humanos , Interferon gama/fisiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise
12.
J Infect Dis ; 184(10): 1315-9, 2001 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11679921

RESUMO

SEN virus (SENV) is a recently discovered group of DNA viruses whose members (SENV-D and SENV-H) are linked to posttransfusion hepatitis. Of 397 injection drug users (IDUs) in Baltimore, Maryland, SENV-D infection was detected by polymerase chain reaction in serum samples from 130 (32.7%) and SENV-H infection in 149 (37.5%). Of 41 IDUs in whom SENV-D DNA was initially detected, retesting for viral persistence a median of 9.3 years later detected SENV-D in 25 (61.0%), whereas SENV-H was detected on retesting in only 14 (26.9%) of 52 IDUs in whom the virus was originally found. Reinfection was apparent (>5% nucleotide difference) in 77.8% of IDUs who repeatedly tested positive for SENV-D DNA and in 55.6% of those who repeatedly tested positive for SENV-H DNA. Among Baltimore IDUs, SENV-D and SENV-H infections are common and dynamic, including both viral clearance and reinfection. The clinical significance of SENV infection in this setting remains unknown.


Assuntos
Infecções por Vírus de DNA/virologia , Vírus de DNA/isolamento & purificação , Hepatite Viral Humana/virologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Baltimore/epidemiologia , Estudos de Coortes , Infecções por Vírus de DNA/epidemiologia , Infecções por Vírus de DNA/fisiopatologia , Vírus de DNA/classificação , Vírus de DNA/genética , DNA Viral/análise , Feminino , Hepatite Viral Humana/epidemiologia , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Prevalência
13.
JAMA ; 286(2): 196-207, 2001 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-11448283

RESUMO

CONTEXT: The continued release of human immunodeficiency virus type 1 (HIV-1) into plasma at very low levels during highly active antiretroviral therapy (HAART) can be detected using specialized techniques, but the nature and significance of this low-level viremia, especially as related to acquisition of drug resistance mutations, are unclear. OBJECTIVE: To determine genetic resistance profiles of low-level plasma HIV-1 in patients with prolonged viral suppression (<50 copies/mL of plasma HIV-1 RNA) while receiving HAART. DESIGN AND SETTING: Cross-sectional study conducted at a US academic hospital from November 1999 to February 2001 using a novel method for amplification of low levels of viral genomes in plasma. PATIENTS: Eighteen HIV-1-infected patients (7 children and 11 adults), enrolled in a longitudinal study of HIV-1 reservoirs, who had suppression of viral replication while receiving protease inhibitor-containing combination therapy. Two patients (1 adult and 1 child) with less optimal suppression of viral replication were included to assess virus predominating when plasma HIV-1 RNA levels are low but detectable (<1000 copies/mL). Follow-up analyses were conducted in 3 patients. MAIN OUTCOME MEASURE: Detection of drug resistance mutations in clones amplified from low-level plasma virus. RESULTS: Viral sequences were amplified from 8 of the 18 patients with simultaneous plasma HIV-1 measurements of less than 50 copies/mL and from 2 patients with 231 and 50 copies/mL. Clones from 3 treatment-naive patients with less than 50 copies/mL of plasma HIV-1 RNA showed continued release, for as long as 42 months, of wild-type drug-sensitive virus. The 7 patients with prior nonsuppressive therapy, with viral loads below 50 copies/mL and during "blips" to 231 and 64 copies/mL, had only resistance mutations consistent with pre-HAART therapy (although reverse transcriptase inhibitor mutations may have continued to occur). New HAART-related mutations were seen in a control patient with prior viral load levels of about 400 to 1000 copies/mL. For phylogenetic analysis, sequences were available for both resting CD4(+) T cells and plasma HIV for 7 of 10 patients and showed patient-specific clustering of sequences and a close relationship between virus in the plasma and the latent reservoir. CONCLUSIONS: Based on the samples that could be amplified, low-level viremia in children and adults receiving HAART with prolonged suppression of viremia to less than 50 copies/mL of HIV-1 RNA may result primarily from archival, pre-HAART virus, reflecting earlier treatment conditions, and does not appear to require development of new, HAART-selected mutations reflecting partial resistance to therapy. Low-level viremia below 50 copies/mL may represent less of a concern regarding impending drug failure of current HAART regimens. However, the archival drug-resistant virus may be relevant regarding future treatment strategies.


Assuntos
Fármacos Anti-HIV/farmacologia , Resistência Microbiana a Medicamentos/genética , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Viremia/fisiopatologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Criança , Pré-Escolar , Estudos Transversais , Feminino , Produtos do Gene pol/genética , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , RNA Viral/sangue , Carga Viral , Viremia/diagnóstico
14.
J Virol ; 75(7): 3259-67, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11238852

RESUMO

When chronic hepatitis C virus (HCV) infections are complicated by acquisition of human immunodeficiency virus (HIV), liver disease appears to accelerate and serum levels of HCV RNA may rise. We hypothesized that HIV might affect the HCV quasispecies by decreasing both complexity (if HIV-induced immunosuppression lessens pressure for selecting HCV substitutions) and the ratio of nonsynonymous (d(N)) to synonymous (d(S)) substitutions, because d(N) may be lower (if there is less selective pressure). To test this hypothesis, we studied the evolution of HCV sequences in 10 persons with chronic HCV infection who seroconverted to HIV and, over the next 3 years, had slow or rapid progression of HIV-associated disease. From each subject, four serum specimens were selected with reference to HIV seroconversion: (i) more than 2 years prior, (ii) less than 2 years prior, (iii) less than 2 years after, and (iv) more than 2 years after. The HCV quasispecies in these specimens was characterized by generating clones containing 1 kb of cDNA that spanned the E1 gene and the E2 hypervariable region 1 (HVR1), followed by analysis of clonal frequencies (via electrophoretic migration) and nucleotide sequences. We examined 1,320 cDNA clones (33 per time point) and 287 sequences (median of 7 per time point). We observed a trend toward lower d(N)/d(S) after HIV seroconversion in 7 of 10 subjects and lower d(N)/d(S) in those with rapid HIV disease progression. However, the magnitude of these differences was small. These results are consistent with the hypothesis that HIV infection alters the HCV quasispecies, but the number of subjects and observation time may be too low to characterize the full effect.


Assuntos
Infecções por HIV/virologia , Soropositividade para HIV , Hepacivirus/classificação , Hepatite C Crônica/virologia , Adulto , Contagem de Linfócito CD4 , DNA Complementar/análise , DNA Complementar/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
15.
Int J Syst Evol Microbiol ; 51(Pt 6): 2145-2165, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11760958

RESUMO

The genera Anaplasma, Ehrlichia, Cowdria, Neorickettsia and Wolbachia encompass a group of obligate intracellular bacteria that reside in vacuoles of eukaryotic cells and were previously placed in taxa based upon morphological, ecological, epidemiological and clinical characteristics. Recent genetic analyses of 16S rRNA genes, groESL and surface protein genes have indicated that the existing taxa designations are flawed. All 16S rRNA gene and groESL sequences deposited in GenBank prior to 2000 and selected sequences deposited thereafter were aligned and phylogenetic trees and bootstrap values were calculated using the neighbour-joining method and compared with trees generated with maximum-probability, maximum-likelihood, majority-rule consensus and parsimony methods. Supported by bootstrap probabilities of at least 54%, 16S rRNA gene comparisons consistently clustered to yield four distinct clades characterized roughly as Anaplasma (including the Ehrlichia phagocytophila group, Ehrlichia platys and Ehrlichia bovis) with a minimum of 96.1% similarity, Ehrlichia (including Cowdria ruminantium) with a minimum of 97.7% similarity, Wolbachia with a minimum of 95.6% similarity and Neorickettsia (including Ehrlichia sennetsu and Ehrlichia risticii) with a minimum of 94.9% similarity. Maximum similarity between clades ranged from 87.1 to 94.9%. Insufficient differences existed among E. phagocytophila, Ehrlichia equi and the human granulocytic ehrlichiosis (HGE) agent to support separate species designations, and this group was at least 98.2% similar to any Anaplasma species. These 16S rRNA gene analyses are strongly supported by similar groESL clades, as well as biological and antigenic characteristics. It is proposed that all members of the tribes Ehrlichieae and Wolbachieae be transferred to the family Anaplasmataceae and that the tribe structure of the family Rickettsiaceae be eliminated. The genus Anaplasma should be emended to include Anaplasma (Ehrlichia) phagocytophila comb. nov. (which also encompasses the former E. equi and the HGE agent), Anaplasma (Ehrlichia) bovis comb. nov. and Anaplasma (Ehrlichia) platys comb. nov., the genus Ehrlichia should be emended to include Ehrlichia (Cowdria) ruminantium comb. nov. and the genus Neorickettsia should be emended to include Neorickettsia (Ehrlichia) risticii comb. nov. and Neorickettsia (Ehrlichia) sennetsu comb. nov.


Assuntos
Anaplasmataceae/classificação , Proteínas de Bactérias/genética , Chaperoninas/genética , RNA Ribossômico 16S/genética , Rickettsiaceae/classificação , Anaplasma/classificação , Anaplasma/genética , Anaplasmataceae/genética , Animais , DNA Ribossômico/genética , Ehrlichia/classificação , Ehrlichia/genética , Ehrlichia ruminantium/classificação , Ehrlichia ruminantium/genética , Humanos , Dados de Sequência Molecular , Filogenia , Rickettsiaceae/genética , Alinhamento de Sequência , Análise de Sequência de DNA
16.
J Virol ; 74(19): 9028-38, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10982347

RESUMO

The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein has been controversially implicated in the inherent resistance of HCV to interferon (IFN) antiviral therapy in clinical studies. In this study, the relationship between NS5A mutations and selection pressures before and during antiviral therapy and virologic response to therapy were investigated. Full-length NS5A clones were sequenced from 20 HCV genotype 1-infected patients in a prospective, randomized clinical trial of IFN induction (daily) therapy and IFN plus ribavirin combination therapy. Pretreatment NS5A nucleotide and amino acid phylogenies did not correlate with clinical IFN responses and domains involved in NS5A functions in vitro were all well conserved before and during treatment. A consensus IFN sensitivity-determining region (ISDR(237-276)) sequence associated with IFN resistance was not found, although the presence of Ala(245) within the ISDR was associated with nonresponse to treatment in genotype 1a-infected patients (P<0.01). There were more mutations in the 26 amino acids downstream of the ISDR required for PKR binding in pretreatment isolates from responders versus nonresponders in both HCV-1a- and HCV-1b-infected patients (P<0.05). In HCV-1a patients, more amino acid changes were observed in isolates from IFN-sensitive patients (P<0.001), and the mutations appeared to be concentrated in two variable regions in the C terminus of NS5A, that corresponded to the previously described V3 region and a new variable region, 310 to 330. Selection of pretreatment minor V3 quasispecies was observed within the first 2 to 6 weeks of therapy in responders but not nonresponders, whereas the ISDR and PKR binding domains did not change in either patient response group. These data suggest that host-mediated selective pressures act primarily on the C terminus of NS5A and that NS5A can perturb or evade the IFN-induced antiviral response using sequences outside of the putative ISDR. Mechanistic studies are needed to address the role of the C terminus of NS5A in HCV replication and antiviral resistance.


Assuntos
Antivirais/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Interferons/administração & dosagem , Ribavirina/administração & dosagem , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , Quimioterapia Combinada , Humanos , Dados de Sequência Molecular , Mutação
17.
J Infect Dis ; 182(3): 698-707, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10950762

RESUMO

Hepatitis C virus (HCV) infection is a major health problem in Egypt, where the seroprevalence is 10-20-fold higher than that in the United States. To characterize the HCV genotype distribution and concordance of genotype assessments on the basis of multiple genomic regions, specimens were obtained from blood donors in 15 geographically diverse governorates throughout Egypt. The 5' noncoding, core/E1, and NS5B regions were amplified by reverse transcription-polymerase chain reaction and analyzed by both restriction fragment length polymorphism (RFLP) and phylogenetic tree construction. For the 5' noncoding region, 122 (64%) of 190 specimens were amplified and analyzed by RFLP: 111 (91%) were genotype 4, 1 (1%) was genotype 1a, 1 (1%) was genotype 1b, and 9 (7%) could not be typed. Phylogenetic analyses of the core/E1 and NS5B regions confirmed the genotype 4 preponderance and revealed evidence of 3 new subtypes. Analysis of genetic distance between isolates was consistent with the introduction of multiple virus strains 75-140 years ago, and no clustering was detected within geographic regions, suggesting widespread dispersion at some time since then.


Assuntos
Hepacivirus/genética , Hepatite C/genética , Doadores de Sangue , Egito/epidemiologia , Genótipo , Hepatite C/epidemiologia , Humanos , Filogenia , Polimorfismo de Fragmento de Restrição , RNA Polimerase Dependente de RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estudos Soroepidemiológicos , Proteínas do Envelope Viral/genética , Proteínas não Estruturais Virais/genética
18.
J Virol ; 74(7): 3058-66, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10708420

RESUMO

The putative envelope 2 (E2) gene of hepatitis C virus (HCV) contains a highly variable region referred to as hypervariable region 1 (HVR1). We hypothesized that this genetic variability is driven by immune selection pressure, rather than representing the accumulation of random mutations in a region with relatively little functional constraint. To test this hypothesis, we examined the E2 sequence of a human inoculum that was passaged through eight chimpanzees, which appear to have a replicative rate (opportunity for chance mutation) similar to that of humans. Acute-phase plasma samples from a human (the inoculum) and six of eight serially infected chimpanzees were studied. For each, 33 cloned cDNAs were examined by a combined heteroduplex-single-stranded conformational polymorphism assay to assess quasispecies complexity and optimize selection of clones with unique gel shift patterns (clonotypes) for sequencing. The sequence diversity of HCV was significantly lower in the chimpanzees than in the humans, and during eight serial passages there was no change in the sequence of the majority clonotype from each animal examined. Similarly, the rates of protein sequence altering (nonsynonymous) substitution were lower in the chimpanzees than in the humans. These findings demonstrate that nonsynonymous mutations indicate selection pressure rather than being an incidental result of HCV replication.


Assuntos
Hepacivirus/fisiologia , Mutação , Proteínas do Envelope Viral/genética , Replicação Viral/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Primers do DNA , Humanos , Dados de Sequência Molecular , Pan troglodytes , Filogenia , Polimorfismo Conformacional de Fita Simples , Homologia de Sequência de Aminoácidos , Inoculações Seriadas
19.
J Infect Dis ; 181(3): 844-51, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10720503

RESUMO

To test the hypothesis that person-to-person variability in blood levels of hepatitis C virus (HCV) RNA can be explained, the quantity of HCV RNA was assessed in 969 persons who acquired HCV infection in the context of injection drug use. Serum HCV RNA levels ranged from 200,000 to >120 million equivalents/mL (the linear range of the assay). The median log10 HCV RNA level was 0.46 higher in 468 human immunodeficiency virus (HIV)-positive persons than in 501 HIV-negative persons (P<.001). In addition, among HIV-negative persons, lower HCV RNA levels were independently associated with younger age (P<.001), ongoing hepatitis B infection (P=.005), and the absence of needle sharing (P=.02). However, >90% of the person-to-person HCV RNA level variability was not explained by these sociodemographic, environmental, and virologic factors. Additional research is necessary to ascertain what determines the level of HCV RNA in blood.


Assuntos
Hepacivirus/genética , RNA Viral/sangue , Adulto , Idoso , Sequência de Aminoácidos , Feminino , Infecções por HIV/virologia , Hepacivirus/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fatores de Tempo
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