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At least 811 records · Page 45Linked to original sources
PubMed2005

Comparative genomic analysis reveals a novel mitochondrial isoform of human rTS protein and unusual phylogenetic distribution of the rTS gene.

BACKGROUND: The rTS gene (ENOSF1), first identified in Homo sapiens as a gene complementary to the thymidylate synthase (TYMS) mRNA, is known to encode two protein isoforms, rTSalpha and rTSbeta. The rTSbeta isoform appears to be an enzyme responsible for the synthesis of signaling molecules involved in the down-regulation of thymidylate synthase, but the exact cellular functions of rTS genes are largely unknown. RESULTS: Through comparative genomic sequence analysis, we predicted the existence of a novel protein isoform, rTS, which has a 27 residue longer N-terminus by virtue of utilizing an alternative start codon located upstream of the start codon in rTSbeta. We observed that a similar extended N-terminus could be predicted in all rTS genes for which genomic sequences are available and the extended regions are conserved from bacteria to human. Therefore, we reasoned that the protein with the extended N-terminus might represent an ancestral form of the rTS protein. Sequence analysis strongly predicts a mitochondrial signal sequence in the extended N-terminal of human rTSgamma, which is absent in rTSbeta. We confirmed the existence of rTS in human mitochondria experimentally by demonstrating the presence of both rTSgamma and rTSbeta proteins in mitochondria isolated by subcellular fractionation. In addition, our comprehensive analysis of rTS orthologous sequences reveals an unusual phylogenetic distribution of this gene, which suggests the occurrence of one or more horizontal gene transfer events. CONCLUSION: The presence of two rTS isoforms in mitochondria suggests that the rTS signaling pathway may be active within mitochondria. Our report also presents an example of identifying novel protein isoforms and for improving gene annotation through comparative genomic analysis.

Amino Acid Sequence↗
PubMed1979

Detection of drugs using XAD-2 resin. I:Choice of resin, chromatographic conditions, and recovery studies.

Amberlite XAD-2, a nonionic polystyrene divinylbenzene resin, was first used for the analysis of drugs in urine and a number of reports have described the development at optimal conditions for extraction, including type of resin columns, pH conditions, and eluting solvents. XAD-4 and XAD-7 resins were compared to the similarly structured XAD-2 resin and no significant advantage over the XAD-2 resin for drug screening was observed. A quantity of 5 to 6 g of resin was found to have sufficient capacity for the extraction of 200 ml of pentobarbital solution (1 mg/100ml). A column flow rate of approximately 15 ml/min (gravitational flow) was sufficient for analysis and slower rates were not more efficient. A mixture of ethyl acetate and 1,2-dichloroethane (3:2) was found to give best overall recovery (66 to 94%) of drugs, the resulting extracts being reasonably free of interfering substances. A pH value of 8.5 is recommended as optimum for comprehensive analysis of acidic and basic drugs. Recovery studies were conducted on spiked samples to determine drug losses occuring during various steps in the XAD-2 extraction procedure for four acidic (amobarbital, secobarbital, pentobarbital, and phenobarbital) and four basic (morphine, codeine, meperidine, and methadone) drugs. A relatively small amount (0 to 5%) of the drugs was not adsorbed by the resin and amounts varying from 6 to 40% failed to be desorbed by the eluting solvent. Additional losses occurred during the removal and analysis of TLC spots. Recovery of drugs from aqueous solutions analyzed with the XAD-2 resin were compared to recoveries reported in the literature with other XAD-2 resin methods for the extraction of drugs from urine. Recovery of phenobarbital, morphine, and codeine improved by 4 to 23% while recoveries of amobarbital, pentobarbital, secobarbital, methadone, and meperidine were 4 to 28% less efficient when compared to literature data.

Barbiturates↗
PubMed2006

Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus.

The influenza pandemic of 1918-19 was responsible for about 50 million deaths worldwide. Modern histopathological analysis of autopsy samples from human influenza cases from 1918 revealed significant damage to the lungs with acute, focal bronchitis and alveolitis associated with massive pulmonary oedema, haemorrhage and rapid destruction of the respiratory epithelium. The contribution of the host immune response leading to this severe pathology remains largely unknown. Here we show, in a comprehensive analysis of the global host response induced by the 1918 influenza virus, that mice infected with the reconstructed 1918 influenza virus displayed an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology. We found that mice infected with a virus containing all eight genes from the pandemic virus showed marked activation of pro-inflammatory and cell-death pathways by 24 h after infection that remained unabated until death on day 5. This was in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes and show that study of the virulence of the 1918 influenza virus requires the use of the fully reconstructed virus. With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and their potential to cause a worldwide pandemic with disastrous health and economic consequences, a comprehensive understanding of the global host response to the 1918 virus is crucial. Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel antiviral therapies.

Animals↗
PubMed2026

narrowPASEF: A Sample-Aware diaPASEF Method Optimization Strategy Improving Differential Proteomics Performance on Low-Abundance Proteins.

Recent instrumental and computational innovations in mass-spectrometry-based proteomics offer new promise in biomarker discovery, thanks to unprecedented proteome coverage and depth. Data-independent acquisition (DIA) methods are very promising in this context as they allow improved proteome coverage, reduced missing value rates, and enhanced quantification precision. However, DIA methods also suffer from their own challenges, such as increased data complexity, cycle times, and background noise. In this work, we propose a sample-aware diaPASEF method optimization strategy for a timsTOF platform. Thorough method optimizations have first been conducted on standard HeLa lysates. Then, a ground-truth calibrated sample series, consisting of a range of UPS amounts spiked into a complex Arabidopsis background, was used to mimic differential analyses under controlled conditions. These benchmark experiments demonstrate clear benefits of using narrowPASEF for differential protein discovery. Finally, our strategy was applied to real use case biological samples to conduct a differential analysis of purified mouse astrocyte cells across two different conditions. narrowPASEF improved the proteome depth by 13%, considering proteins quantified with a coefficient of variation (CV) of <20%, and led to a 68% (435 vs 729) increase in differentially expressed proteins. These results provide an opportunity for a more precise and comprehensive analysis of the biological functions of biomarkers, offering a more profound understanding of the disease mechanisms. The benefits of our sample-aware narrowPASEF strategy demonstrated the most substantial impact on low-abundance proteins. Overall, these results show promise for more valuable and robust biomarker discoveries in the future.

Proteomics↗
PubMed1992

Classification of nonspecific low back pain. II. Clinical diversity of organic forms.

A classification study was conducted in an unselected sample of outpatient subjects with localized nonspecific low back pain. The heterogeneity of a subgroup of patients without a psychiatric disorder according to the DSM-III classification (axis I), and whose low back pain may be labeled as 'purely organic' (see part 1 of the study in the companion paper), led to further evaluation of this group by correspondence and cluster analysis. A seven-cluster population structure emerged from the cluster analysis. Comprehensive description of these clusters suggests at least four well-differentiated clinical entities or 'syndromes.' Although no satisfactory correlation with pre-existing 'pathoanatomic' classification or hypotheses was found, this variable clinical presentation suggests different etiological or physiopathologic patterns for low back pain (and possibly more specific management of this condition). More comprehensive descriptions and evaluations of clinical symptoms and syndromes appear necessary in order to elaborate a clinical classification of LBP.

Acute Disease↗
PubMed2025

Genome-Wide Identification, Phylogenetic Analysis, and Expression Pattern of Polyamine Biosynthesis Gene Family in Pepper.

Polyamines (PAs), including putrescine, spermidine, spermine, and thermospermine, play essential roles in plant growth, development, and responses to stress. However, the structure and function of PA biosynthetic genes in pepper remain poorly characterized. This study aimed to identify PA biosynthesis genes in the pepper genome using bioinformatics approaches and to assess their expression under various stress conditions. A total of 16 PA biosynthesis-related genes were identified, representing members of the arginine decarboxylase (ADC), ornithine decarboxylase (ODC), agmatine iminohydrolase (AIH), N-carbamoylputrescine amidohydrolase (CPA), S-adenosylmethionine decarboxylase (SAMDC), spermidine synthase (SPDS), spermine synthase (SPMS), and ACAULIS5 (ACL5) gene families. These genes encode proteins with an average molecular weight of approximately 40 kDa, primarily localized in the mitochondria and cytoplasm. Promoter analysis revealed multiple cis-acting elements associated with stress and phytohormone responsiveness. Gene expression was induced by various abiotic stresses, including saline-alkaline, drought, heat, cold, and hydrogen peroxide, as well as by phytohormones such as abscisic acid, ethylene, salicylic acid, auxin, and gibberellin. Overall, this study provides a comprehensive analysis of PA biosynthesis genes in pepper and highlights their potential roles in stress adaptation and hormone signalling, offering a foundation for further exploration of PA-mediated stress tolerance mechanisms.

Capsicum↗
PubMed2007

Integrative genomic analysis reveals distinct transcriptional and genetic features associated with chromosome 13 deletion in multiple myeloma.

BACKGROUND AND OBJECTIVES: The chromosome 13 deletion (Delta13) is one of the most frequent chromosomal alterations in multiple myeloma (MM). Delta13 is associated with an unfavorable prognosis, although there is increasing agreement that its prognostic relevance must be related to the ploidy status and the presence of different chromosomal translocations. The aim of this study was to provide a comprehensive analysis of the transcriptional features of Delta13 in MM. DESIGN AND METHODS: Highly purified plasma cells from 80 newly diagnosed MM patients were characterized by means of fluorescence in situ hybridization (FISH) and high-density oligonucleotide microarray for gene expression profiling and chromosomal alterations. RESULTS: We identified 67 differentially expressed genes in the patients with and without the chromosome 13 deletion, all of which were downregulated in the cases with Delta13: 44 mapped along the whole chromosome 13, seven on chromosome 11 and three on chromosome 19. Functional analyses of the selected genes indicated their involvement in protein biosynthesis, ubiquitination and transcriptional regulation. An integrative genomic approach based on regional analyses of the gene expression data identified distinct chromosomal regions whose global expression modulation could differentiate Delta13-positive cases, in particular the upregulation of 1q21-1q42 and the downregulation of 19p and almost the entire chromosome 11. FISH analyses confirmed the close relationship between Delta13-positivity and the presence of extra copies of 1q21-1q42 (p=6 x 10(-4)) or the absence of chromosome 11 and 19 trisomy (p=5 x 10(-4)). INTERPRETATION AND CONCLUSIONS: Our results indicate that distinct types of chromosomal aberrations are closely related to the transcriptional profiles of Delta13-positive cases, suggesting that the contribution of Delta13 to the malignancy should be considered together with associated abnormalities.

Adult↗
PubMed1992

[The management procedure for patients with cholelithiasis and the results of rehabilitative treatment after cholecystectomy based on polyclinic observations].

Based on an analysis of the dynamic ultrasonic, biochemical and hormonal data on 550 patients operated on for cholelithiasis and comparison of preoperative and pathomorphological diagnoses, indications for surgical treatment of cholelithiasis patients in the stage of so-called "lithocarriership" were developed and a group at risk for cancer was identified as well. A comprehensive analysis of the clinical and instrumental data on 185 patients operated on for cholelithiasis, made in the long-term periods (from 1 to 3 years) after cholecystectomy indicates the efficacy of differentiated rehabilitation treatment, including elderly subjects and the necessity of early surgical treatment of cholelithiasis before there may develop irreversible alterations in the choledochus, liver and pancreas and in the gallbladder itself. Comparison of the dynamic ultrasonic data, liver and pancreas functions and factors such as sex, age, obesity and physical exercise makes it possible to predict the course of cholelithiasis to a certain degree of probability at the asymptomatic stage and to specify the policy of managing such patients under ambulatory conditions.

Absenteeism↗
PubMed2005

Mutations and deletions of the CBP gene in human lung cancer.

PURPOSE: Microarray-based comparative genomic hybridization analysis led us to detect a homozygous deletion at the cyclic AMP response element binding protein-binding protein (CBP) locus in a lung cancer cell line. Oncogenic roles of CBP had been suggested by functional and genetic studies; thus, involvement of CBP gene alterations in lung carcinogenesis was investigated by undertaking comprehensive analysis of genetic CBP alterations in human lung cancer. EXPERIMENTAL DESIGN: Fifty-nine cell lines and 95 surgical specimens of lung cancer were analyzed for mutations, homozygous and hemizygous deletions, and expression of the CBP gene. RESULTS: Homozygous CBP deletions, including two intragenic deletions, were detected in three (5.1%) lung cancer cell lines. CBP mutations, including missense, nonsense, and frame-shift mutations, were detected in six (10.2 %) cell lines and five (5.3%) surgical specimens of lung cancer. The wild-type CBP allele was retained in 9 of 11 cases with CBP mutations, and both the wild-type and mutant alleles were expressed in all the six cases with heterozygous CBP mutations examined. Three mutations with amino acid substitutions in the histone acetyltransferase domain caused significant reduction in transcription activation activity of CBP protein in vivo. CONCLUSIONS: A fraction of lung cancers carried mutations and/or deletions of the CBP gene, suggesting that genetic CBP alterations are involved in the genesis and/or progression of a subset of lung cancers.

Acetyltransferases↗
PubMed1994

Expression of the c-met protooncogene in human hepatocellular carcinoma.

The c-met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c-met expression in hepatocarcinogenesis is suspected. In this study, we examined c-met expression in 23 hepatocellular carcinoma cases by means of Northern-blot analysis and an immunohistochemical study. Northern-blot analysis revealed c-met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c-met protein was detected in 16 of 23 patients (69.6%). With both methods, c-met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c-met protein expression was correlated with poor-to-moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki-67 labeling index. All cases with increased tumor proliferative activity showed c-met protein expression, although the elevation of proliferative activity in the c-met-positive group was not statistically significant. These data suggest that the overexpression of c-met plays an important role in the development of hepatocellular carcinoma.

Adult↗
PubMed2006

Systems for the detection and analysis of protein-protein interactions.

The analysis of protein-protein interactions is important for developing a better understanding of the functional annotations of proteins that are involved in various biochemical reactions in vivo. The discovery that a protein with an unknown function binds to a protein with a known function could provide a significant clue to the cellular pathway concerning the unknown protein. Therefore, information on protein-protein interactions obtained by the comprehensive analysis of all gene products is available for the construction of interactive networks consisting of individual protein-protein interactions, which, in turn, permit elaborate biological phenomena to be understood. Systems for detecting protein-protein interactions in vitro and in vivo have been developed, and have been modified to compensate for limitations. Using these novel approaches, comprehensive and reliable information on protein-protein interactions can be determined. Systems that permit this to be achieved are described in this review.

Chromatography, Affinity↗
PubMed2007

Lipidomic analysis for lipid peroxidation-derived aldehydes using gas chromatography-mass spectrometry.

A lipidomic method is described for the measurement of lipid peroxidation-derived aldehydes using gas chromatography/electron ionization/mass spectrometry with selected ion monitoring (GC/EI/MS-SIM). Aldehydes in the samples were converted into their pentafluorobenzyl (PFB)-oximes using PFB-hydroxylamine, and other functional groups such as the hydroxyl groups were further derivatized into the trimethylsilyl ethers. The PFB-oxime derivatives could be comprehensively detected by the SIM of m/z 181, which is a characteristic fragment ion of the PFB-oxime derivatives. At the same time, each aldehyde was classified into five groups (alkanals, 2-alkenals, 2,4-alkadienals, 2-hydroxyalkanals, and 4-hydroxy-2-alkenals) by SIM of the structure-specific fragment ions. Determination of the 4-hydroxy-2-alkenals was also performed by confirmation of their higher reactivity with the sulfhydryl group. On the basis of the mass spectrometric characterization, we have identified at least 33 aldehydes formed upon the FeII-mediated decomposition of the arachidonic acid-, linoleic acid-, and docosahexaenoic acid-hydroperoxides in vitro. We then applied this system to the in vivo samples and successfully observed the increase in aldehydes in the liver of mice intraperitoneally injected with bromobenzene, an experimental animal model for lipid peroxidation. Using this comprehensive analysis, unique differences in the formation between each aldehyde could be observed. This method is useful for simultaneously monitoring the lipid peroxidation-derived aldehydes formed under oxidative stress in vivo.

Aldehydes↗
PubMedDate not supplied

Mutation in a sex-determining gene in rainbow trout: detection and genetic analysis.

In rainbow trout (Oncorhynchus mykiss), the acknowledged sex-determining system is genetic sex determination (GSD) with female homogamety (female symbolXX-male symbolXY). Subsequently, mitotic gynogens are all expected to be females. Unexpected maleness was fortuitously observed in a mitotic gynogenetic family of rainbow trout (13 males out of 27). An equal ratio of males and females suggested the possible segregation of some Mendelian sex-influencing factor. In order to perform a comprehensive analysis of the inheritance and expression of the factor involved, the transmission of maleness was studied across the next three generations, using both conventional and/or meiotic and mitotic gynogenetic offspring. On the whole, males as well as intersexes were observed in crosses between two expected carrier parents, and in gynogenetic offspring of expected carrier females, but not in crosses between one expected carrier parent and one normal XX control. Sex ratios in the different crosses often fitted Mendelian proportions, but not always. Both excess and lack of maleness were observed. The simplest hypothesis consistent with most results is a one-locus model, assuming the existence of a mutation (termed mal) of a sex-determining gene, which is able to override the primary XX mechanism of sex determination and to induce the development of testicular tissue in the gonads of expected XX individuals. The one-locus model requires that the mal mutation usually, but not systematically, behave as a recessive mutation and have a limited penetrance, that is, heterozygous (mal/+) may be sex reversed, homozygous (mal/mal) may remain female, and carrier individuals may undergo partial masculinization alone (many intersexes were recorded). Inconsistency in sex ratios among offspring of parents expected to respond the same way was recorded, indicating that other modifier loci may also be involved. Finally, the occurrence of both males and females in clonal progenies showed that epigenetic factors also likely influence the expression of maleness. The effects of the mal mutation are compared to similar mutations recently described in other fish species. The nature and location of the mal gene (carried by heterochromosomes or an autosomal pair) is briefly discussed in view of the knowledge recently acquired on the subject.

Animals↗
PubMed2005

Microarray analysis of gene expression in cultured skin substitutes compared with native human skin.

Cultured skin substitutes (CSS), prepared using keratinocytes, fibroblasts, and biopolymers, can facilitate closure of massive burn wounds by increasing the availability of autologous tissue for grafting. But because they contain only two cell types, skin substitutes cannot replace all of the functions of native human skin. To better understand the physiological and molecular differences between CSS and native skin, we undertook a comprehensive analysis of gene expression in native skin, cultured keratinocytes, cultured fibroblasts, and skin substitutes using Affymetrix gene chip microarrays. Hierarchical tree clustering identified six major clusters of coordinately regulated genes, using a list of 1030 genes that were the most differentially expressed between groups. These clusters correspond to biomarker pools representing expression signatures for native skin, fibroblasts, keratinocytes, and cultured skin. The expression analysis revealed that entire clusters of genes were either up- or downregulated upon combination of fibroblasts and keratinocytes in cultured skin grafts. Further, several categories of genes were overexpressed in CSS compared with native skin, including genes associated with hyperproliferative skin or activated keratinocytes. The observed pattern of expression indicates that CSS in vitro, which display a well-differentiated epidermal layer, exhibit a hyperproliferative phenotype similar to wounded native skin.

Cluster Analysis↗
PubMed2026

[Optical genome mapping analysis of a Chinese pedigree with a complex balanced translocation involving four chromosomes].

OBJECTIVE: To explore the genetic characteristics of a complex balanced translocation involving four non-homologous chromosomes in a Chinese pedigree using optical genomic mapping (OGM). METHODS: A woman with primary infertility and her family members who presented at the Prenatal Diagnosis Center of the Sixth Affiliated Hospital of Sun Yat-sen University in October 2021 were selected as study subjects. Comprehensive analysis and verification of chromosomal abnormalities were conducted through conventional G-band karyotyping analysis, single nucleotide polymorphism microarray (SNP array) and OGM. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: E2022210). RESULTS: G-band karyotyping analysis indicated that the proband, her father, and younger brother have all carried a complex translocation involving four chromosomes. SNP array analysis revealed a duplication of approximately 21.63 Mb in the 9p24.1-p21.1 region in the proband's younger brother, while no abnormality was detected in other family members. OGM confirmed that the complex balanced translocation has involved chromosomes 5, 8, 9, and 10. CONCLUSION: The proband has harbored a complex balanced translocation. OGM has demonstrated certain advantages in characterization of complex chromosomal structural abnormalities.

Humans↗
PubMed1992

Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd autoantibody positive connective tissue disease patients.

OBJECTIVE: We have recently found that the presence of autoantibodies against the 70-kd polypeptide of U1 RNP (U1-70-kd) is associated with HLA-DR4 and DR2. To further characterize this association, we performed a molecular genetic analysis of HLA-DR and DQ genes among patients with autoantibodies against U1-70-kd. METHODS: The polymerase chain reaction (PCR), sequence-specific oligonucleotide hybridization, and solid-phase direct DNA sequencing of PCR-amplified DNA were utilized to analyze HLA-DRB1, DRB5, DQA1, and DQB1 genes. RESULTS: A comprehensive analysis of HLA-DRB1, DRB5, DQA1, and DQB1 from 27 patients and controls identified shared amino acids FDYFYQA (Phe, Asp, Tyr, Phe, Tyr, Gln, Ala) at positions 26, 28, 30-32, 70, and 73 of HLA-DRB1 on disease-associated haplotypes. CONCLUSION: A common cluster of shared amino acids, or a shared epitope, identified within HLA-DRB1 among anti-U1-70-kd autoantibody positive connective tissue disease patients may be important in regulating an autoimmune response to the U1-70-kd antigen.

Amino Acid Sequence↗
PubMed2006

Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis.

Serotonin 2A receptor (5-HT2A) gene was implicated to be associated with both schizophrenia and suicidal behavior due to its role of key neurotransmitter in many physiologic processes. Association studies were reported in different populations, however, a great number of subsequent studies have produced contrary results, possibly reflecting inadequate statistical power. With the cumulative data in recent years in both European and Asian populations, particularly in Asian populations, it was necessary to carry out a comprehensive analysis of previous findings. The meta-analysis, therefore, combined all English and Chinese studies using multiple research methods published up to July 2005 to give a new picture of the role of the 5-HT2A gene. Compared with significant results reported previously, the current large samples (73 studies in all) failed to find significant association of the T102C polymorphism with either schizophrenia or suicidal behavior. Evidence of significant association was only detected between A-1438G and suicidal behavior. The current study did not support the association of the 5-HT2A gene with either schizophrenia or suicidal behavior.

Alleles↗
PubMed2005

Full-breadth analysis of CD8+ T-cell responses in acute hepatitis C virus infection and early therapy.

Multispecific CD8(+) T-cell responses are thought to be important for the control of acute hepatitis C virus (HCV) infection, but to date little information is actually available on the breadth of responses at early time points. Additionally, the influence of early therapy on these responses and their relationships to outcome are controversial. To investigate this issue, we performed comprehensive analysis of the breadth and frequencies of virus-specific CD8(+) T-cell responses on the single epitope level in eight acutely infected individuals who were all started on early therapy. During the acute phase, responses against up to five peptides were identified. During therapy, CD8(+) T-cell responses decreased rather than increased as virus was controlled, and no new specificities emerged. A sustained virological response following completion of treatment was independent of CD8(+) T-cell responses, as well as CD4(+) T-cell responses. Rapid recrudescence also occurred despite broad CD8(+) T-cell responses. Importantly, in vivo suppression of CD3(+) T cells using OKT3 in one subject did not result in recurrence of viremia. These data suggest that broad CD8(+) T-cell responses alone may be insufficient to contain HCV replication, and also that early therapy is effective independent of such responses.

Acute Disease↗