BACKGROUND: Rapid, sensitive, specific, and cost-effective screening of donated blood to prevent transmission of infectious agents remains challenging. In recent years, incorporation of nucleic acid testing for HIV-1 and HCV RNA improved blood safety by reducing the window period between infection and serologic detection. For HBV infection, this window period with most serologic assays is 50-60 days. Adding a nucleic acid test (NAT) for HBV DNA with existing NATs for HIV-1 and HCV RNA would further improve blood safety and blood screening efficiency. OBJECTIVE: To evaluate the Procleix Ultrio Assay for simultaneous detection of HIV-1 and HCV RNA and HBV DNA and corresponding discriminatory assays. STUDY DESIGN: The performance of these assays, which utilize the same technology and assay format as the Procleix HIV-1/HCV assay, was determined using relevant clinical specimens and analytical sensitivity and specificity panels. RESULTS: The Procleix Ultrio Assay demonstrated specificity of > or =99.5% in healthy donor blood specimens and in plasma containing potentially interfering substances or other blood-borne pathogens. Assay sensitivity demonstrated >95% detection of 100copies/mL, 30IU/mL, and 15IU/mL for HIV-1 and HCV RNA, and HBV DNA, respectively. The assay detects all known HIV-1 subtypes and HCV and HBV genotypes and is highly reproducible. Statistical analysis using receiver operating characteristic plots demonstrated wide analyte cutoff values for each assay associated with assay specificity and sensitivity of > or =99.5%. CONCLUSIONS: In this investigational study, the Procleix Ultrio Assay sensitivity and specificity were similar to existing NATs used in blood-bank settings to detect HIV-1 and HCV RNA and provided equivalent sensitivity and specificity for detection of HBV DNA. Using this combination assay, blood safety may be improved and the multiplex format enhances blood screening efficiency. The throughput capability of this assay is compatible with large volume processing and the chemistry is adaptable to full automation. 相似文献
The present study aimed to investigate the relationship between the disturbed balance of CD4+/CD8+, Th17/Treg and the activation of the Notch signaling pathway in experimental autoimmune uveitis (EAU).
Methods
An EAU rat model was induced in Lewis rats, and pathology analysis was performed by hematoxylin and eosin (H&E) staining. CD4+, CD8+, Th17, and Treg levels in spleen, lymph nodes and eye tissues were determined by flow cytometry. Meanwhile, the expression of Notch1, DLL4, IL-10, and IL-17 was determined by quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, the inhibitory effect of N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT) on Th17 differentiation by Notch signaling in vitro was further investigated using T lymphocytes from EAU rats on day 12 post-immunization by flow cytometry.
Results
The pathological results showed that inflammatory cell infiltration occurred in ocular tissues in EAU rats. The CD4+/CD8+ and Th17/Treg ratios in EAU rats were apparently higher than those in normal control individuals. Q-PCR and ELISA analyses indicated the expression of Notch1, DLL4, IL-10, and IL-17 in EAU rats gradually increased on day 6 after immunization, peaked on day 12, and then gradually decreased. The dynamic trends in Notch1 and DLL4 expression in EAU rats were identical to those of CD4+/CD8+ and Th17/Treg levels. DAPT can significantly inhibit the activation of Notch signaling, decrease Th17 cell differentiation, and attenuate the level of the Th17 cell lineage, contributing to the balance of the Th17/Treg ratio.
Conclusion
The activation of the Notch signaling pathway can regulate Th17 and Treg cell differentiation, disrupt the CD4+/CD8+ and Th17/Treg balance, and aggravate the severity of EAU; inactivation of the Notch signaling pathway contributes to the CD4+/CD8+ and Th17/Treg balance in EAU rats. Our findings highlighted that the dynamic change in the CD4+/CD8+ and Th17/Treg ratio was consistent with the expression trend of Notch signaling in EAU rats, suggesting that Notch signaling may be a potentially important therapeutic target in clinical practice.
OBJECTIVE: To investigate the relationship between the plasminogen activator inhibitor (PAI-1) polymorphisms and endometrial hypoplasia in infertile women. METHODS: The study was conducted in 105 primary infertile patients with endometrial hypoplasia diagnosed by pathology and the thickness of endometrium by B-mode ultrasound and 85 controls who were not pregnant and had normal fertility. The -675 4G/5G polymorphism in the PAI-1 gene was detected by polymerase chain reaction-restriction fragment length polymerphim analysis. RESULTS: The frequencies of 4G/4G genotype and 4G allele of the PAI-1 gene were higher in the patient group (48.6% and 66.2%) than in the normal controls (22.4% and 47.1%) (P < 0.01). ThePAI-1 4G/4G genotype was significantly associated with endometrial hypoplasia in the infertile patients (OR=4.9, 95% CI: 2.10-10.12). CONCLUSION: The present findings suggest that the 4G/5G polymorphism of the PAI-1 gene was associated with endometrial hypoplasia in infertile patients. 相似文献
Lattice constants (LCs) of all possible 96 apatite compounds, A(5)(BO(4))(3)C, constituted by A[double bond]Ba(2+), Ca(2+), Cd(2+), Pb(2+), Sr(2+), Mn(2+); B[double bond]As(5+), Cr(5+), P(5+), V(5+); and C[double bond]F(1-), Cl(1-), Br(1-), OH(1-), are predicted from their elemental ionic radii, using pattern recognition (PR) and artificial neural networks (ANN) techniques. In particular, by a PR study it is demonstrated that ionic radii predominantly govern the LCs of apatites. Furthermore, by using ANN techniques, prediction models of LCs a and c are developed, which reproduce well the measured LCs (R(2)=0.98). All the literature reported on 30 pure and 22 mixed apatite compounds are collected and used in the present work. LCs of all possible 66 new apatites (assuming they exist) are estimated by the developed ANN models. These proposed new apatites may be of interest to biomedical research especially in the design of new apatite biomaterials for bone remodeling. Similarly these techniques may also be applied in the study of interface growth behaviors involving other biomaterials. 相似文献
BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE), a prototype of systemic autoimmune disease characterized by multiorgan involvement with diverse clinical and serological manifestations, principally affects women in their child-bearing years. Clinically significant hepatic abnormality as the initial presentation of SLE has rarely been reported. METHODS: Eleven patients with lupus with initial presentation of lupus-related hepatitis were included in this retrospective review. Clinical manifestation, immunological profiles, and risk factors for poor prognosis were analyzed. RESULTS: The most commonly associated clinical manifestations were found to be thrombocytopenia, leukopenia, advancing age, and presence of anti-SSA/Ro antibody and anti-thyroid antibodies. The diagnosis of SLE was delayed due to dominant hepatic abnormalities. Age greater than 50 years and marked hepatic decompensation in accordance with Child classification B and C might suggest poor prognosis (p=0.06). However, the p value was not statistically significant because of the small sample size. CONCLUSIONS: Lupus-related hepatitis, particularly in late-onset lupus, is common. In addition, the presence of anti-SSA, anti-thyroglobulin, and anti-microsomal antibodies is indicative of hepatic involvement in patients with SLE. 相似文献
Spouse-spouse, sib-sib, and parent-offspring correlations were calculated for urinary, plasma, and intracellular sodium levels on over 1,900 persons aged 3-86 years in 98 Utah kindreds. For 36 hours prior to their clinic visit, 31% of the sample was salt-loaded with salt tablets, while the rest followed their normal diet. For those on their normal diet, urine creatine-, age-, and sex-adjusted urinary sodium excretion from a timed 12-hour overnight sample showed similar and significant correlations between spouses (r = .29), sibs less than 20 years old (r = .38), and parent-offspring pairs for offspring less than 20 years old (r = .29). This contrasted with the lower correlations between sibs 20 years of age and older (r = .10) and parent-offspring pairs for offspring 20 years of age and older (r = .13), presumed to live in different households. Adult plasma sodium sib-sib (r = .13) and parent-offspring (r = .15) correlations were similar to the urinary sodium correlations, while the spouse-spouse (r = .48), the sib-sib (r = .64), and the parent-offspring (r = .63) correlations for those presumed to live in the same household nearly doubled. Intracellular sodium correlations for the adult sibs (r = .32) and offspring (r = .36) were over twice as large as for urinary or plasma sodium, although the spouse-spouse correlation (r = .37) remained large also.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
In the present study, we used both histidine decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1 h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that α-fluoromethylhistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine–histidine–histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future. 相似文献
We report here the molecular cloning of a newly identified preprotachykinin gene, Pptc, which specifies the sequence for a new preprotachykinin protein and bioactive peptide designated hemokinin 1 (HK-1). PPT-C mRNA was detected primarily in hematopoietic cells in contrast to the previously described Ppta and Pptb genes, which are predominantly expressed in neuronal tissues. HK-1 has several biological activities that are similar to the most studied tachykinin, substance P, such as induction of plasma extravasation and mast cell degranulation. However, HK-1 also has properties that are indicative of a critical role in mouse B cell development. HK-1 stimulated the proliferation of interleukin 7-expanded B cell precursors, whereas substance P had no effect. HK-1, but not substance P, promoted the survival of freshly isolated bone marrow B lineage cells or cultured, lipopolysaccharide-stimulated pre-B cells. N-acetyl-L-trytophan-3,5-bistrifluromethyl benzyl ester, a tachykinin receptor antagonist, increased apoptosis of these cells and in vivo administration of this antagonist led to specific reductions of the B220lowCD43 population (the pre-B cell compartment) in the bone marrow and the IgMhighIgDlow population (the newly generated B cells) in the spleen. Thus, HK-1 may be an autocrine factor that is important for the survival of B cell precursors at a critical phase of development. 相似文献