Asymptomatic Carriers Group Research Articles

Effects of HTLV-1 on leukocyte trafficking and migration in ACs compared to healthy individuals

Human T-lymphotropic virus type 1 (HTLV-1) is a RNA virus belonging to Retroviridae family and is associated with the development of various diseases, including adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Aside from HAM/TSP, HTLV-1 has been implicated in the development of several disorders that mimic auto-inflammation. T-cell migration is important topic in the context of HTLV-1 associated diseases progression. The primary objective of this case–control study was to assess the relationship between increased mRNA expression in virus migration following HTLV-1 infection. PBMCs from 20 asymptomatic patients and 20 healthy subjects were analyzed using real-time PCR to measure mRNA expression of LFA1, MLCK, RAC1, RAPL, ROCK1, VAV1 and CXCR4. Also, mRNA expression of Tax and HBZ were evaluated. Mean expression of Tax and HBZ in ACs (asymptomatic carriers) was 0.7218 and 0.6517 respectively. The results revealed a noteworthy upregulation of these genes involved in T-cell migration among ACs patients in comparison to healthy individuals. Considering the pivotal role of gene expression alterations associated with the progression into two major diseases (ATLL or HAM/TSP), analyzing the expression of these genes in the ACs group can offer probable potential diagnostic markers and aid in monitoring the condition of ACs.

A longitudinal 18F‐FDG PET study in asymptomatic stage of genetic Creutzfeldt–Jakob disease

AbstractBackgroundPathogenic prion protein may start to deposit in some brain regions and cause functional alterations in the asymptomatic stages in Creutzfeldt–Jakob disease patients. However, the disease trajectory of Creutzfeldt–Jakob disease in the asymptomatic stage and when and where the degenerative process begins are still not clear.MethodsAt baseline, we enrolled five asymptomatic mutation carriers, six affected genetic Creutzfeldt–Jakob diseasepatients, and 23 healthy controls from whom 18F fluorodeoxyglucose‐positron emission tomography, clinical, and neuropsychological measures were acquired. Only five asymptomatic mutation carriers had completed longitudinal follow‐up. We set three‐time points to identify the changing trajectory in asymptomatic carriers group including baseline, 2‐year and 4‐year follow‐up.ResultsAt baseline, the cerebral glucose metabolic rate, measured as the standardized uptake value rate ratio, clinical and neuropsychological scales in all 5 asymptomatic cases were normal. In the 4‐years follow‐up, hypometabolic brain regions in asymptomatic genetic Creutzfeldt–Jakob disease group were found in the insula, frontal, parietal, and temporal lobes (false discovery rate corrected p<0.01). The standardized uptake value rate ratio changing trajectories of all asymptomatic cases were within the range between the healthy controls and affected patients. Notably, the metabolism values of one asymptomatic individual whose baseline age was older than the expected age of onset showed a rapid decline and approached the mean value of genetic Creutzfeldt–Jakob disease condition at the last follow‐up.ConclusionOur study illustrates that neurodegenerative process associated with genetic Creutzfeldt–Jakob disease may involve the insula, frontal, temporal, and parietal lobes before clinical presentation of the disease, and the decline will accelerate when close to the expected age of onset. Although there are no effective means to cure this fatal disease, the time interval before clinical disease onset may aid important trials or therapies intended to slow or halt the disease process.

Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population

Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions.

A Review on Prophylactic Regimen by Evaluation of Asymptomatic SARS CoV-II Carriers

The coronavirus disease 19(COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-II), which emerged in Wuhan, China and spread around the world. It is considered a relative of Severe Acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), The cause of COVID-19 is a beta coronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. The Asymptomatic carriers have become the current focus of global epidemic prevention and control efforts. These carriers of the virus display no clinical symptoms but are known to be contagious. As "silent spreaders", asymptomatic carriers warrant attention as a part of disease prevention and control. The comparable viral load in a group of asymptomatic carriers of COVID-19 was found to be higher than that of the symptomatic carriers. There are numerous micronutrients which are essential for immunocompetence, particularly Vitamin A, C, D, E, B, iron, selenium, and zinc. Immunonutrition refers to the modulation of the immune system through the modification of dietary nutrients. Vitamins A to E highlighted potentially beneficial roles in the fight against COVID-19 via antioxidant effects, immunomodulation, enhancing natural barriers, and local paracrine signaling. The present review provides a brief information on supplementation of Immunonutrients in form of vitamins which ultimately can act as prophylactic regimen for Asymptomatic carriers of SARS CoV-II virus.

A longitudinal 18F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

BackgroundPathogenic prion protein may start to deposit in some brain regions and cause functional alterations in the asymptomatic stage in Creutzfeldt–Jakob disease. The study aims to determine the trajectory of the brain metabolic changes for prion protein diseases at the preclinical stage.MethodsAt baseline, we enrolled five asymptomatic PRNP G114V mutation carriers, six affected genetic PRNP E200K CJD patients and 23 normal controls. All participants completed clinical, diffusion-weighted imaging (DWI) and 18F fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) examinations. Longitudinal follow-up was completed in five asymptomatic mutation carriers. We set three-time points to identify the changing trajectory in the asymptomatic carriers group including baseline, 2-year and 4-year follow-up.ResultsAt baseline, DWI signals, the cerebral glucose standardized uptake value rate ratio (SUVR) and clinical status in 5 asymptomatic cases were normal. At the follow-up period, mild hypometabolism on PET images was found in asymptomatic carriers without any DWI abnormal signal. Further group quantitatively analysis showed hypometabolic brain regions in the asymptomatic genetic CJD group were in the insula, frontal, parietal, and temporal lobes in 4-year follow-up. The SUVR changing trajectories of all asymptomatic cases were within the range between the normal controls and affected patients. Notably, the SUVR of one asymptomatic individual whose baseline age was older showed a rapid decline at the last follow-up.ConclusionsOur study illustrates that the neurodegenerative process associated with genetic CJD may initiate before the clinical presentation of the disease.

Association of the rs4143815 polymorphism of PDL1 gene with HTLV-1 infection and proviral load in asymptomatic blood donors in northeast Iran.

It is obvious that genetic differences, including mutations and polymorphisms, can play an important role in viral infections. In this case-control study, which included 81 human T-cell leukemia virus type 1 (HTLV-1) asymptomatic carriers (AC) and 162 healthy controls (HC), the rs4143815 polymorphism of PDL1 gene was investigated. This polymorphism is the site of miR-570 binding and it can influence immune system responses. The rs4143815 polymorphism was evaluated by allele-specific polymerase chain reaction (AS-PCR) and the proviral load levels by quantitative real-time PCR (q PCR). The results demonstrated that the C allele (P = 0.027) and the CC genotype (P = 0.031) of rs4143815 polymorphism was significantly higher in the AC group than in the HC group, also the proviral load in the AC group with the C allele (P = 0.020) was significantly higher. Thus, the rs4143815 polymorphism can play a vital role in HTLV-1 infection.

Clinical Application Value of Combined Detection of CG and TBA in Differential Diagnosis of Hepatobiliary System Diseases

Objective: To understand the clinical value of combined detection of cholyglycine CG and TBA in differential diagnosis of hepatobiliary diseases. Methods: Serum samples from 50 healthy people were collected as healthy control group. According to the latest disease diagnosis and treatment plan, 58 cases of HBV asymptomatic carrier group, 17 cases of viral hepatitis group, 49 cases of cirrhosis group, 50 cases of primary liver cancer group and 50 cases of other hepatobiliary diseases groups were collected respectively. The concentration levels of cholyglycine and total bile acid in each group were detected, and the differences among each group were compared. Results: By statistical analysis, serum CG concentration in viral hepatitis group, cirrhosis group, primary liver cancer group and other hepatobiliary diseases group was significantly higher than that in asymptomatic HEPATITIS B carriers and healthy control group, the differences were statistically significant (p 0.05). There was no significant difference in CG concentration among viral hepatitis group, liver cirrhosis group, primary liver cancer group and other hepatobiliary diseases group (p > 0.05). The serum TBA levels of asymptomatic carriers, viral hepatitis group, cirrhosis group, primary liver cancer group and other hepatobiliary system diseases group were significantly higher than those of healthy control group, the difference was statistically significant, p 0.05. Conclusion: Serum CG expression can not only detect liver lesions, but also distinguish different liver lesions. The positive rate of CG combined with TBA detection in patients with hepatobiliary diseases is significantly higher than that of single CG index detection. CG combined with TBA detection can significantly improve the sensitivity and accuracy of the diagnosis of hepatobiliary diseases, which is worthy of popularization and application.

The association of polymorphisms (rs2227981 and rs10204525) of PDCD1 gene with susceptibility to human T-cell leukemia virus type 1

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus as the causative agent of two serious diseases in human is known.Programmed cell death-1 (PD-1) is a regulatory protein that has an important role in immune system response and created exhaustion phenotype in T cells at chronic infections; therefore, it can impair anti-viral responses. Since the single nucleotide polymorphisms (SNP) in PD-1gene may influence infection with HTLV-1virus, so in this research, association between SNPs in exon 5 of PD-1 gene with susceptibility to HTLV-1 infection and proviral load (PVL) in Iran's population studied. In this case-control study, PD-1 rs2227981 and rs10204525 polymorphisms were evaluated in 81 HTLV-1 asymptomatic carriers (ACs) and 162 healthy individuals (control groups). These polymorphisms were genotyped by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Moreover, PVL was detected by quantitative real-time PCR (Q-RT-PCR). The results indicated that frequency of GA and AA genotypes in rs10204525 polymorphism was higher in ACs group (82.7%) than control group (26.5%) significantly; and GA + AA genotypes were significantly associated with HTLV-1 infection (OR = 13.244, 95%CI = 6.755–25.968, p = 0.000); but CT + TT genotypes in rs2227981 polymorphism, were as a protective factor against HTLV-1 infection (OR = 0.473, 95%CI = 0.279–0.813, P = 0.009). However, there was no significant difference between these polymorphisms and HTLV-1 PVL.

Gene Expression of Lysosomal Membrane Proteins in Parkinson Disease, Associated with Mutations in the Glucocerebrosidase Gene (GBA)

Introduction. In carriers of a mutation in the lysosomal enzyme glucocerebrosidase ( GBA ) gene, the risk of Parkinson disease (PD) is increased by 7–8 times. However, not all carriers of the GBA gene mutations develop PD during their lifetime. We hypothesize that the dysfunction in the lysosomal membrane proteins involved in autophagy and transport of GBA into the lysosomes can contribute to the development of PD in carriers of mutations in the GBA gene. The aim of the study was to assess the contribution of LAMP2 and SCARB2 genes expression in CD45 + peripheral blood cells to the development of GBA-PD. Materials and methods. We examined 9 patients with GBA-PD, 9 asymptomatic GBA gene mutations carriers, 37 patients with PD, and 56 people in the control group. The relative mRNA level of LAMP2 and SCARB2 genes in CD45 + blood cells, obtained using magnetic sorting, was measured by quantitative real-time polymerase chain reaction using fluorescent probes. Results. The relative mRNA level of LAMP2 and SCARB2 genes in CD45 + blood cells was reduced in patients with GBA-PD in comparison to patients with PD and to controls ( LAMP2: p<0.0001, p = 0.01 respectively; SCARB2: p = 0.01, p<0.05, respectively) and in asymptomatic carriers of GBA gene mutations compared to patients with PD ( LAMP2: p = 0.021; SCARB2: p<0.05) and controls ( LAMP2: p = 0.029). We also found decreased mRNA levels of the LAMP2 gene (p = 0.024) and the absence of differences in the mRNA levels of the SCARB2 gene (р<0.05) in CD45 + blood cells in patients with GBA-PD when compared to the group of asymptomatic carriers of GBA gene mutations. Conclusion. GBA-PD is characterized by a pronounced expression of the LAMP2 gene in the CD45 + peripheral blood cells, which may indicate a role of the decreased LAMP2 gene expression in the pathogenesis of GBA-PD.

Comparison of pre-S1/S2 variations of hepatitis B virus between asymptomatic carriers and cirrhotic/hepatocellular carcinoma-affected individuals.

Aim of the studyHost and viral factors can influence the clinical course of chronic hepatitis B virus (HBV) infection. Mutations in pre-S1/S2 gene regions are among the most important viral factors determining the HBV infection outcome. The aim of this study was to investigate the role of pre-S1/S2 mutations in HBV infection outcome.Material and methodsA total of 52 samples from 26 asymptomatic carriers (ASCs) and 26 liver cirrhosis/hepatocellular carcinoma (LC/HCC) patients were enrolled. The HBV DNA genome was extracted from the sera, and pre-S1/S2 regions of the samples were amplified by nested-polymerase chain reaction, prior to being subjected to sequencing, sequence investigation and phylogenetic analysis.ResultsCertain deletions were detected mostly located at the boundary of the pre-S1 and pre-S2 regions. These deletions were detected more frequently in ASC cases than in LC/HCC patients (p < 0.007). The rate of critical point mutations, including L11Q, N37S and K38R, was significantly higher in the ASC group, whereas the A49V substitution rate was significantly higher in the LC/HCC group (p < 0.05). The phylogenetic analysis indicated that all the sequences belonged to genotype D.ConclusionsAccording to the results, point mutations such as L11Q, N37S, K38R and A49V, as well as certain deletions, may be associated with HBV infection outcome, among an HBV genotype D pure population.

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients.

BackgroundAdult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL.MethodsForty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR.ResultsSignificant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047).ConclusionThe HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

Higher Serum Levels of Rheumatoid Factor and Anti-Nuclear Antibodies in Helicobacter Pylori-Infected Peptic Ulcer Patients

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p<0.05). Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (p<0.05). Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

Vitamin D and Tumor Necrosis Factor-Alpha Receptor Gene Polymorphisms in Various Hepatitis B Clinical Conditions in Turkey.

BackgroundThe aim is to define the role of single nucleotide polymorphism on the progress of hepatitis B virus (HBV) infection. We evaluated polymorphisms of TNF-α-308, Vitamin D receptor Apa I and Taq I gene in patients with HBV infection.MethodsAll subjects included were older than 18 years old. Sixty three patients had chronic HBV infection, 61 were HBsAg positive carriers and 59 were positive for anti-HBs and anti-HBc. Gene polymorphisms were evaluated by Amplification Refractory Mutation System PCR. For patients with chronic hepatitis, viral load, ALT levels, and histopathological evaluation of the liver were also compared.ResultsGender distribution was not different among groups; however, anti-HBs positive patients were significantly older than the other patients. ALT levels and viral load were significantly higher in chronic hepatitis group than the asymptomatic carriers group. Vitamin D receptor Apa I gene and Taq I gene and TNF-α -308 gene variant alleles were not different in all three groups. Variant alleles of three genes were not different in subgroups of chronic hepatitis patients formed according to ALT levels, viral load, histological activity index, and fibrosis score.ConclusionsRole of single nucleotide polymorphism in clinical status of various HBV infection states was not shown in this study. Considering the other studies performed with this aim, which strengthens the notion that ethnicity is an important factor, future studies with more patients from different ethnic groups may help to clear the role of polymorphisms in the clinical progress of HBV infection.

Anti-Tax antibody levels in asymptomatic carriers, oligosymptomatic carriers, patients with rheumatologic disease or with HAM/TSP do not correlate with HTLV-1 proviral load

Background HTLV-1 infects millions of people around the world and induces myelopathy (HAM/TSP), adult T-cell leukemia (ATL) or other inflammatory or rheumatologic diseases. The host–virus interaction causes asymptomatic carriers to develop HAM/TSP. Biomarkers are needed to predict patients who are at risk for HAM/TSP. Tax is highly immunogenic and is a major target protein recognized by cytotoxic T lymphocytes. Anti-Tax antibodies are involved in HAM/TSP pathogenesis. Objectives To assess anti-Tax IgG reactivity with a flow cytometry assay (FCA) using an infection/transfection system with Vaccinia virus and pLW44/Tax-expressing Tax and to correlate the anti-Tax response and the HTLV-1 proviral load. Study design : We enrolled 81 individuals: 9 HTLV-1 seronegative (NP) and 72 HTLV-1 positive (23 HTLV-1 asymptomatic carriers (AC), 12 oligosymptomatic patients (OL), 7 with rheumatologic diseases (DR) and 30 with HAM/TSP (HT)). Anti-Tax reactivity was assessed by FCA, and HTLV-1 proviral load was measured with real time PCR. Results The HT and DR groups showed greater anti-Tax IgG reactivity ( p < 0.001 and p < 0.05 comparing HT to the OL and AC group, respectively; p < 0.05 comparing DR to the OL group), and the reactivity in the DR + HT group was significantly different when compared to the AC group ( p < 0.05) and to the OL group ( p < 0.001). The proviral load was higher in the HT group compared to the OL ( p < 0.001) and in the HT + DR group compared to OL ( p < 0.001). There was no correlation between anti-Tax IgG reactivity and proviral load in any of the HTLV-1-infected groups. Conclusion These findings suggest that although anti-Tax IgG reactivity and the HTLV-1 proviral load are important markers of the development of HTLV-1-associated diseases, their levels are not correlated.

Visual evoked potentials findings in non-affected subjects from a large Brazilian pedigree of 11778 Leber’s hereditary optic neuropathy

To investigate pattern-reversal visual evoked potentials (PRVEP) in asymptomatic maternally and non-maternally related members from a large Brazilian 11778/ND4 LHON pedigree. Transient PRVEP for check sizes 15' and 60' were recorded from asymptomatic mutation carriers and non-mutant descendants of affected/non-affected males, all with best-corrected visual acuity of 20/20. A control group of spouses (off-pedigree) was also included. Parameters of N75, P100 and N135 latencies (ms) and N75-P100 peak-to-peak amplitude (μV) as well as temporal dispersion (latency of N135-latency of N75) were determined. Longitudinal testing was obtained in a subseries of carriers in three annual consecutive visits. We tested 48 asymptomatic mutation carriers, 19 descendants of affected males, 9 descendants of non-affected males and 27 off-pedigrees, all of the latter being non-mutant. All non-mutant male descendants did not differ from off-pedigree controls. Statistically prolonged P100 latencies were found in mutation carriers (P=0.0143) when compared with off-pedigrees for check sizes 15', as well as significantly larger temporal dispersions for both check size 15' (P=0.0012) and check size 60' (P=0.0271). Serial testing in 15 mutation carriers disclosed prolonged P100 latencies and larger temporal dispersion that did not change over time. Subclinical PRVEP abnormalities were detected in this large group of asymptomatic carriers of the 11778/ND4 LHON mutation from the same family, confirming and extending previous psychophysical and structural findings of a selective involvement of the parvocellular pathway. PRVEP is a useful test to characterize and monitor visual dysfunction in this devastating disease.

The efficiency of immunoenzyme assay in the diagnosis of lambliosis

Abstract The aim of this study is to determine the difference in efficiency of direct immunoenzyme-linked assay (EIA) and conventional microscopy (CM) plus conventional concentration technique (CCT) using comparative analysis in the diagnosis of symptomatic and asymptomatic lambliosis when only one stool sample is to be tested. The study enrolled 577 examinees: 208 patients and 369 asymptomatic examinees. Lambliosis was diagnosed using CM plus CCT (three stool samples) and direct EIA (the first sample). All statistical parameters of the EIA method were 100% in the patients with symptoms of infection. In addition to that, in the group of asymptomatic carriers of Giardia lamblia (G. lamblia) some very high values of these parameters were recorded too, with sensitivity and negative predictive value being both at 100%. In contrast to the EIA method, CM plus CCT of the first stool sample demonstrated significantly lower sensitivity (66.67%) compared to the reference standard. The study did not demonstrate any statistically significant differences in diagnostic efficiancy between the EIA testing of one stool sample and CM plus CCT (p&lt;0.05). However, the observed difference in diagnostic efficiency between the methods was very close to the cut-off value for statistical significance (p=0.06).

Clinical significance of pre‐S mutations in patients with genotype C hepatitis B virus infection

We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.

Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection.

To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha), gene promoter and hepatitis B (HB) viral genotypes were associated with outcomes of HBV infection. A total of 244 HBV self-limited infected subjects, 208 asymptomatic carriers, and 443 chronic HB patients were recruited to conduct a case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and HBV genotypes were examined by nested PCR. The positive rate of HBV DNA in asymptomatic carrier group and chronic HB group was 46.6% and 49.9%, respectively. HBV genotype proportion among the asymptomatic carriers was 2.1% for genotype A, 25.8% for genotype B, 68.0% for genotype C, and 4.1% for genotype B+C mixed infection, and 0.9% for genotype A, 21.7% for genotype B, 71.5% for genotype C, 5.9% for genotype B+C mixed infection in chronic HB group. There was no significant difference in genotype distribution between the asymptomatic carrier group and chronic HB group (chi2 = 1.66, P = 0.647). The frequency of -238GG genotype in self-limited group was 95.1%, significantly higher than 90.7% in chronic HB group and 89.0% in asymptomatic carrier group (P = 0.041 and P = 0.016, respectively). The frequency of TNF-alpha-857 CC in chronic HB group was 79.7%, significantly higher than 64.4% in asymptomatic carrier group and 70.9% in self-limited group (P<0.001 and P = 0.023, respectively). A multiple logistic regression analysis revealed that TNF-alpha-238GA and -857CC were independently associated with chronic HB after gender and age were adjusted. TNF-alpha promoter variants are likely to play a substantial role in the outcome of HBV infection.

Increased proviral load in HTLV-1-infected patients with rheumatoid arthritis or connective tissue disease

BackgroundHuman T-lymphotropic virus type 1 (HTLV-1) proviral load is related to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been shown to be elevated in the peripheral blood in HTLV-1-infected patients with uveitis or alveolitis. Increased proliferation of HTLV-1-infected cells in, or migration of such cells into, the central nervous system is also seen in HAM/TSP. In the present study, we evaluated the proviral load in a cohort of HTLV-1-infected patients with arthritic conditions.ResultsHTLV-1 proviral load in the peripheral blood from 12 patients with RA and 6 patients with connective tissue disease was significantly higher than that in matched asymptomatic HTLV-1 carriers, but similar to that in matched HAM/TSP controls. HAM/TSP was seen in one-third of the HTLV-1-infected patients with RA or connective tissue disease, but did not account for the higher proviral load compared to the asymptomatic carrier group. The proviral load was increased in the synovial fluid and tissue from an HTLV-1-infected patient with RA, the values suggesting that the majority of infiltrated cells were HTLV-1-infected. In the peripheral blood from HTLV-1-infected patients with RA or connective tissue disease, HTLV-1 proviral load correlated with the percentages of memory CD4+ T cells and activated T cells, and these percentages were shown to be markedly higher in the synovial fluid than in the peripheral blood in an HTLV-1-infected patient with RA.ConclusionsThese biological findings are consistent with a role of the retrovirus in the development of arthritis in HTLV-1-infected patients. A high level of HTLV-1-infected lymphocytes in the peripheral blood and their accumulation in situ might play a central role in the pathogenesis of HTLV-1-associated inflammatory disorders. Alternatively, the autoimmune arthritis, its etiological factors or treatments might secondarily enhance HTLV-1 proviral load.

Striatal Hypertrophy: A Mechanism for Preclinical Compensation in Parkin-Associated Parkinsonism?

18F-Fluorodopa (F-DOPA) positron emission tomography (PET) demonstrated a reduction of striatal F-DOPA uptake in asymptomatic carriers of heterozygous Parkin mutations, indicating a latent dopaminergic dysfunction in the basal ganglia. We used voxel-based morphometry of high-resolution structural magnetic resonance images in a comparable group of asymptomatic Parkin mutation carriers to investigate whether this latent dopaminergic dysfunction is associated with structural abnormalities in the motor system. Structural MR data (T1-weighted FLASH 3D MR sequences; TE=5 ms; TR=15 ms; flip angle=30°; isotropic voxel size 1×1 x 1mm3) of 13 right handed asymptomatic carriers of heterozygous mutations in the Parkin gene (eight females, mean age: 38.6±5.8yrs, range: 28–47yrs) were compared with those of 13 age-matched healthy controls. MR images were preprocessed and analyzed using SPM2 software (FIL, London, UK). We used an optimized protocol for voxel-based morphometry, which involves non-linear spatial normalization to a customized grey matter template. Images were smoothed with a Gaussian kernel 12mm FWHM. Using a general linear model, voxel-by-voxel t-tests were computed to detect differences in grey matter volume between groups (significance threshold: p<0.01 and p<0.01 for cluster size; Gaussian Random Field theory). All asymptomatic carriers and controls had a normal neurological and neuropsychological examination. Voxel-based morphometry revealed a significant increase in grey matter volume in the left posterior putamen and globus pallidus internus (GPI) [Talairach coordinates: x=–25, y=0, z=3; SVC around the striatum p=0.03, corrected (FDR)]. There was also a subthreshold increase in grey matter volume in the right GPI. The increase in grey matter volume in the posterior striatum showed a close spatial correspondence to the location of dopamine hypometabolism found in the comparable group of asymptomatic carriers in the previous F-DOPA PET study (Hilker et al., 2001). This co-localization may suggest that the increase in grey matter volume might represent a long-term consequence of adaptive plasticity in the basal ganglia. Such an increase in structure might help the motor system to compensate for the preclinical dopaminergic deficit and prevent the manifestation of minor motor symptoms (Brezard et al., 2003). The higher increase in the grey mater density in the left striatum indicates a higher amount of compensation for the dominant right hand.