Mother-infant hepatitis C transmission: second generation research.
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Adult↗
Biomedical subjects
D L Thomas
Publications and source records attributed to D L Thomas.
Class II HLA alleles and hepatitis B virus persistence in African Americans.
Persistence of hepatitis B virus (HBV) infection is likely due to the interplay of the virus and host immune response. Given its critical role in antigen presentation, allelic differences in the HLA complex may affect HBV persistence. In a prospectively followed African American cohort, molecular class I and class II HLA typing was done on 31 subjects with persistent HBV infection and 60 controls who cleared the infection. HBV persistence was significantly associated with two class II alleles, DQA1 *0501 (odds ratio [OR], 2.6; P=.05) and DQB1 *0301 (OR, 3.9; P=.01), the two-locus haplotype consisting of these same two alleles (OR, 3; P=. 005) and the three-locus haplotype, DQA1 *0501, DQB1 *0301, and DRB1 *1102 (OR, 10.7; P=.01). In addition, HBV persistence was associated with class II allelic homozygosity. Several class I associations with persistence were also noted but were not statistically significant after correction for multiple comparisons. These results underscore the importance of the class II-mediated immune response in recovery from HBV infection.
Adult↗
Hepatitis E: an emerging infectious disease.
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Age Distribution↗
Measuring cerebral blood flow using magnetic resonance imaging techniques.
Magnetic resonance imaging techniques measuring CBF have developed rapidly in the last decade, resulting in a wide range of available methods. The most successful approaches are based either on dynamic tracking of a bolus of a paramagnetic contrast agent (dynamic susceptibility contrast) or on arterial spin labeling. This review discusses their principles, possible pitfalls, and potential for absolute quantification and outlines clinical and neuroscientific applications.
Animals↗
High viral load and mild liver injury in children with hemophilia compared with other children with chronic hepatitis C virus infection.
BACKGROUND: In adults with hepatitis C virus (HCV) infection, the severity of liver disease may be influenced by the mode of transmission. The purpose of this study was to evaluate whether the mode of transmission affects liver injury and viral load in children with chronic HCV infection, independent of duration of infection and/or HCV genotype. METHODS: Thirty-nine anti-HCV (EIA-2) positive patients, were divided into three groups: group 1, children with a history of blood transfusion (n = 9; age, 13.3+/-1.3 years), group 2, children with hemophilia (n = 19; age, 11.6+/-0.8 years); and group 3, children with maternal-fetal transmitted disease (n = 10; age, 4.7+/-1.1 years). Serum alanine aminotransferase, HCV viral load, HCV genotype, and liver histology were assessed. RESULTS: Serum HCV viral load was higher in group 2 (4.27+/-1.0x10(6) copies/ml; p = 0.006) than in group 1 (0.73+/-0.3x10(6) copies/ml) and in group 3 (0.83+/-0.2x10(6) copies/ml). Conversely, group 2 had less severe liver injury compared with children of similar age in group 1 (p = 0.022). Despite a shorter duration of infection, group 3 had liver injury similar to that in group 1. Hepatitis C virus genotype did not influence the level of viremia or liver injury. CONCLUSIONS: Although children with hemophilia exhibited a high HCV viral load, liver histopathology was less severe than in children who had acquired HCV by blood transfusion or maternal-fetal transmission. These observations support the need to investigate the role of host immune response rather than the virus per se in the pathogenesis of HCV infection in children.
Adolescent↗
Viral persistence, antibody to E1 and E2, and hypervariable region 1 sequence stability in hepatitis C virus-inoculated chimpanzees.
The relationship of viral persistence, the immune response to hepatitis C virus (HCV) envelope proteins, and envelope sequence variability was examined in chimpanzees. Antibody reactivity to the HCV envelope proteins E1 or E2 was detected by enzyme-linked immunosorbent assay (ELISA) in more than 90% of a human serum panel. Although the ELISAs appeared to be sensitive indicators of HCV infection in human serum panels, the results of a cross-sectional study revealed that a low percentage of HCV-inoculated chimpanzees had detectable antibody to E1 (22%) and E2 (15%). Viral clearance, which was recognized in 28 (61%) of the chimpanzees, was not associated with an antibody response to E1 or E2. On the contrary, antibody to E2 was observed only in viremic chimpanzees. A longitudinal study of animals that cleared the viral infection or became chronically infected confirmed the low level of antibody to E1, E2, and the HVR-1. In 10 chronically infected animals, the sequence variation in the E2 hypervariable region (HVR-1) was minimal and did not coincide with antibody to E2 or to the HVR-1. In addition, low nucleotide and amino acid sequence variation was observed in the E1 and E2 regions from two chronically infected chimpanzees. These results suggest that mechanisms in addition to the emergence of HVR-1 antibody escape variants are involved in maintaining viral persistence. The significance of antibodies to E1 and E2 in the chimpanzee animal model is discussed.
Amino Acid Sequence↗
Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy.
We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (dN/dS) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charge. Quasispecies complexity was higher and E1 dN/dS ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics. In contrast, a trend toward higher HVR1 dN/dS ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration. HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1.
Acute Disease↗
Early region 1 transforming functions are dispensable for mammary tumorigenesis by human adenovirus type 9.
Some human adenoviruses are tumorigenic in rodents. Subgroup A and B human adenoviruses generally induce sarcomas in both male and female animals, and the gene products encoded within viral early region 1 (E1 region) are both necessary and sufficient for this tumorigenicity. In contrast, subgroup D human adenovirus type 9 (Ad9) induces estrogen-dependent mammary tumors in female rats and requires the E4 region-encoded ORF1 oncoprotein for its tumorigenicity. Considering the established importance of the viral E1 region for tumorigenesis by adenoviruses, we investigated whether this viral transcription unit is also necessary for Ad9 to generate mammary tumors. The nucleotide sequence of the Ad9 E1 region indicated that the gene organization and predicted E1A and E1B polypeptides of Ad9 are closely related to those of other human adenovirus E1 regions. In addition, an Ad9 E1 region plasmid demonstrated focus-forming activity in both low-passage-number and established rat embryo fibroblasts, whereas a large deletion within either the E1A or E1B gene of this plasmid diminished transforming activity. Surprisingly, we found that introducing the same transformation-inactivating E1A and E1B deletions into Ad9 results in mutant viruses that retain the ability to elicit mammary tumors in rats. These results are novel in showing that Ad9 represents a unique oncogenic adenovirus in which the E4 region, rather than the E1 region, encodes the major oncogenic determinant in the rat.
Adenovirus E1 Proteins↗
Reperfusion in a gerbil model of forebrain ischemia using serial magnetic resonance FAIR perfusion imaging.
BACKGROUND AND PURPOSE: Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. METHODS: Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. RESULTS: On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. CONCLUSIONS: The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.
Animals↗
A quantitative method for fast diffusion imaging using magnetization-prepared TurboFLASH.
For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.
Animals↗
Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection.
GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.
Adult↗
Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study.
Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.
Adult↗
Prevalence and incidence of hepatitis C virus infection among young adult injection drug users.
Through community-based outreach, young adult injection drug users (IDUs) were enrolled in a prospective study of the prevalence, incidence, and risk factors for hepatitis C virus (HCV) infection. Demographics and information on sexual and injecting practices were collected during semiannual interviews, and HCV infection was evaluated using a second-generation antibody assay. Of the 229 participants, 86 (37.6%) were HCV-seropositive at baseline. After adjusting for injecting frequency and duration by logistic regression, HCV seroprevalence was independently associated with reusing syringes at least once in the past 6 months (odds ratio [OR]=3.81, 95% confidence interval [CI] 1.39-11.00), injecting the first time with someone > or =5 years older (OR=2.99; 95% CI, 1.43-6.23) or alone (OR=4.02; 95% CI, 1.12-14.43) versus with someone <5 years older, and injecting cocaine or speedball exclusively (OR=4.29; 95% CI, 1.53-12.01) or with other drugs (OR=5.27; 95% CI, 2.62-10.64) versus injecting no cocaine in the past 6 months. Of the 105 originally HCV-seronegative participants who returned for follow-up, 13 seroconverted (incidence rate=16.0/100 person-years). On bivariate analysis, HCV seroconversion was significantly associated with injecting for <2 years (relative risk [RR]=7.3; 95% CI, 1.6-32.8) and continuing to inject during follow-up (RR=4.4; 95% CI, 1.0-19.9). Young adult IDUs are at high risk for HCV infection. These data support the need for wider legal access to sterile syringes, as well as expanded community outreach education to this population to prevent transmission of HCV.
Adult↗
Assessment of hepatitis C virus sequence complexity by electrophoretic mobilities of both single-and double-stranded DNAs.
To assess genetic variation in hepatitis C virus (HCV) sequences accurately, we optimized a method for identifying distinct viral clones without determining the nucleotide sequence of each clone. Twelve serum samples were obtained from seven individuals soon after they acquired HCV during a prospective study, and a 452-bp fragment from the E2 region was amplified by reverse transcriptase PCR and cloned. Thirty-three cloned cDNAs representing each specimen were assessed by a method that combined heteroduplex analysis (HDA) and a single-stranded conformational polymorphism (SSCP) method to determine the number of clonotypes (electrophoretically indistinguishable cloned cDNAs) as a measure of genetic complexity (this combined method is referred to herein as the HDA+SSCP method). We calculated Shannon entropy, incorporating the number and distribution of clonotypes into a single quantifier of complexity. These measures were evaluated for their correlation with nucleotide sequence diversity. Blinded analysis revealed that the sensitivity (ability to detect variants) and specificity (avoidance of false detection) of the HDA+SSCP method were very high. The genetic distance (mean +/- standard deviation) between indistinguishable cloned cDNAs (intraclonotype diversity) was 0.6% +/- 0.9%, and 98.7% of cDNAs differed by <2%, while the mean distance between cloned cDNAs with different patterns was 4.0% +/- 3.2%. The sensitivity of the HDA+SSCP method compared favorably with either HDA or the SSCP method alone, which resulted in intraclonotype diversities of 1.6% +/- 1.8% and 3.5% +/- 3.4%, respectively. The number of clonotypes correlated strongly with genetic diversity (R2, 0.93), but this correlation fell off sharply when fewer clones were assessed. This HDA+SSCP method accurately reflected nucleotide sequence diversity among a large number of viral cDNA clones, which should enhance analyses to determine the effects of viral diversity on HCV-associated disease. If sequence diversity becomes recognized as an important parameter for staging or monitoring of HCV infection, this method should be practical enough for use in laboratories that perform nucleic acid testing.
Cloning, Molecular↗
Seasonal changes in protein composition of whey from commercial manufacture of caprine and ovine specialty cheeses.
Pooled whey from the production of one variety of ovine cheese and two varieties of caprine cheeses was studied for gross composition and individual whey protein composition over one production season. Individual proteins were quantified by sodium dodecyl sulfate-PAGE and digital imaging technology. The mean proportion of alpha-lactalbumin (LA) from caprine wheys from the manufacture of Chevre and Cheddar-type cheeses was higher than values previously reported for bovine whey from Cheddar cheese; proportions of serum albumin, immunoglobulin (Ig)G, and beta-lactoglobulin (LG) were lower. Ovine whey from Manchego-type cheese showed a higher proportion of beta-LG, about the same proportion of alpha-LA, and lower proportions of serum albumin and IgG than did the bovine whey. Relative amounts of alpha-LA decreased throughout the season, but beta-LG rose in midlactation and then gradually decreased toward the end of lactation. Relative proportions of serum albumin remained fairly stable throughout the year, and IgG decreased.
Animals↗
Advance directives in a correctional setting.
Using advance directives to preconsent to mental health treatment is a promising approach to contending with the quandary posed by patients suffering from severe mental health illness, particularly those in a prison setting. The implementation of advance directives represents unfamiliar territory because it focuses on the patient's ability to preconsent to treatment rather than the commonly interpreted prerefusal of treatment. The challenge of consenting in the prison system generates a set of unique problems. The environment in which the instrument is signed can impose significant pressures and therefore result in a viable legal challenge. The prison setting is the most coercive environment in which a patient can be treated, particularly when the patient is mentally ill. Mentally ill prisoners signing preconsent for treatment advance directives have an opportunity for unprecedented relief yet may also experience pressure to select treatments desirable to the prison staff.
Advance Directives↗
Vaccines to prevent viral hepatitis.
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Hepatitis A↗
Focus formation of C3H/10T1/2 cells and exposure to a 836.55 MHz modulated radiofrequency field.
Disruption of communication between transformed cells and normal cells is involved in tumor promotion. We have tested the hypothesis that exposures to radiofrequency (RF) fields using a form of digital modulation (TDMA) and a chemical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), are copromoters that enhance focus formation of transformed cells in coculture with parental C3H/10T1/2 murine fibroblasts. RF field exposures did not influence TPA's dose-dependent promotion of focus formation in coculture. Cell cultures were exposed to an 836.55 MHz TDMA-modulated field in TEM transmission line chambers, with incident energies that simulated field intensities at a user's head. Specific absorption rates (SARs) of 0.15, 1.5, and 15 muW/g were used during each digital packet, and the packet frequency was 50/s. The TEM chambers were placed in a commercial incubator at 37 degrees C and 95% humidity/5% CO2. The RF field exposures were in a repeating cycle, 20 min on, 20 min off, 24 h/day for 28 days. At 1.5 muW/g, TPA-induced focus formation (at 10, 30, and 50 ng/ml) was not significantly different in RF-exposed cultures compared to parallel sham-exposed cultures in ten independent experiments in terms of the number, density, and area of foci. Similarly, at 0.15 and 15.0 muW/g, in two and four experiments, respectively, RF exposure did not alter TPA-induced focus formation. The findings support a conclusion that repeated exposures to this RF field do not influence tumor promotion in vitro, based on the RF field's inability to enhance TPA-induced focus formation.
Analysis of Variance↗