Systematic review and meta-analysis: Development of hepatocellular carcinoma in chronic hepatitis B patients with hepatitis e antigen seroconversion.

Hepatitis B e antigen (HBeAg) seroconversion is considered to have significantly favourable clinical outcomes for patients with chronic hepatitis B (CHB). However, inconsistent study results suggest that hepatocellular carcinoma (HCC) still occurs in patients with HBeAg seroconversion. We performed a systematic review and meta-analysis to determine the incidence of HCC in patients with CHB after HBeAg seroconversion. Web of Science, PubMed and Embase databases were searched through January 2017. The incidence of HCC in CHB patients after HBeAg seroconversion was pooled using a random-effects model or fix-effects model. Sixteen studies were finally included, involving 4910 patients with HBeAg seroconversion. The overall pooled proportion suggested that 3.33% (95% confidence interval (CI): 2.28%-4.58%) of patients with CHB develop HCC despite HBeAg seroconversion. In patients with HBeAg seroconversion without cirrhosis, the pooled proportion of HCC development was 0.94% (95% CI: 0.15%-2.4%). Moreover, patients with cirrhosis, active hepatitis, or aged greater than 40 years at the time of HBeAg seroconversion were at significantly higher risk for HCC development. HBeAg seroconversion was significantly associated with a reduced risk of HCC compared with persistently positive HBeAg (RR = 0.58, 95% CI: 0.35-0.97, P = .04). Despite the reduced risk with HBeAg seroconversion, HCC can still occur in a proportion of patients with CHB after HBeAg seroconversion. Long-term monitoring is needed for patients with established cirrhosis, active hepatitis or those older than 40 years at the time of HBeAg seroconversion.

Postchallenge hyperglycaemic spike associate with arterial stiffness.

Several large-scale epidemiological and intervention studies strongly indicate that postchallenge hyperglycaemia is the main factor associated with increasing the risk of morbidity and mortality in type 2 diabetes. However, the mechanisms that increase the risk of cardiovascular disease remain unclear. We aimed to study the relationship between postchallenge hyperglycaemia and arterial stiffness. We recruited 40 healthy subjects from a physical examination in 2005. Cardio-ankle vascular index (CAVI) was automatically calculated by VaSera VS-1000. For the reliability study, we performed the baseline study in the first 20 subjects who were returned to receive repeated measurements of CAVI 2 weeks later. The determinants of mean CAVI at different timings of oral glucose tolerance test (OGTT) study were analysed by constructing multivariate linear regression models. In reliability test, the inter-observer correlation coefficient was 0.82 for right CAVI, 0.87 for left CAVI and 0.85 for mean CAVI. Age, systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose levels at 60 min (Glu60) and glucose area under the curve of OGTT (GluAUC) are found to be significantly and positively correlated to right CAVI, left CAVI and mean CAVI (p < 0.05). After adjustment for age, gender and SBP, Glu60 and GluAUC are still independent determinants of CAVI. In subjects without clinical diagnosis of type 2 diabetes, postchallenge hyperglycaemic spike is highly associated with CAVI, a good parameter of aortic stiffness, independent of age, gender and blood pressure.

Nitric oxide increased interleukin-4 expression in T lymphocytes.

Nitric oxide (NO) is a regulator of many biological functions including T helper 1 (Th1)/T helper 2 cells balance. It has been demonstrated that NO inhibits the secretion of interleukin-2 (IL-2) and interferon-gamma on Th1 cells. Here we showed that, in addition to the suppression of IL-2 production, NO-generating agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) increased the secretion of IL-4 both in Th2 clones and EL4 T cells. The additive effect was dependent on the dose of SNP and SNAP. Augmentation of IL-4 production was detected with 1 microM SNP, and up to threefold increase in IL-4 secretion could be observed with higher concentrations of SNP/SNAP. NO also weakly increased the activation of IL-4 promoter. In contrast, NO markedly inhibited the induction of IL-2 promoter, which could account for most of the reduction in IL-2 production. Analysis of the transcriptional elements on IL-2 and IL-4 promoters revealed a selective inactivation of NF-kappa B and NF-AT. It is suggested that despite the complex feedback network regulating NO production, the enhanced IL-4 expression would lead to the expansion of Th2 cells once NO is generated.

The binding mode of an E-64 analog to the active site of cathepsin B.

Two binding modes of the isobutyl-NH-Eps-Leu-Pro inhibitor to cathepsin B have been proposed. Molecular docking using an empirical force field was carried out to distinguish between the two modes. The search began with manual docking, followed by random perturbations of the docking conformation and cycles of Monte Carlo minimization. Finally, molecular dynamics was carried out for the most favorable docking conformations. The present calculations predict that the isobutyl-NH-Eps-Leu-Pro inhibitor preferentially binds to the S' rather than the S subsites of cathepsin B. The S' binding mode prediction is supported by the X-ray crystal structure of cathepsin B bound to a closely related ethyl-O-Eps-Ile-Pro inhibitor, which was found to bind in the S'subsite with the C-terminal epoxy ring carbon making a covalent bond to the sulfur atom of Cys29. This agreement, in turn, validates our docking strategy. Furthermore, the calculations provide evidence that the dominant contribution to the total stabilization energy of the enzyme-inhibitor complex stems from the strong electrostatic interaction between the negatively charged C-terminal carboxylate group of the ligand and the positively charged imidazolium rings of His110 and His111. The latter are stabilized and held in an optimal orientation for interactions with the C-terminal end of the ligand through a salt bridge between the side chains of His110 and Asp22. By comparison with the crystal structure, some insight into the specificity of the epoxyldipeptide family towards cathepsin B inhibition has been extracted. Both the characteristics of the enzyme (e.g. subsite size and hydrophobicity) as well as the nature of the inhibitor influence the selectivity of an inhibitor towards an enzyme.

Selective contact during TCR recognition.

Recent structural analysis of the peptide-MHC complex reveals that an antigenic peptide binds to MHC in only one conformation and that side chains anchoring in the binding pocket would not contact TCR. The identification of all the MHC-anchoring residues on an antigenic peptide is a prerequisite to understand how a given peptide interacts with the TCR. In a combination of binding analysis and model simulation, model peptide lambda repressor cl 16-26 was shown to bind to I-Ek through four anchor residues (Leu18, IIe21, Glu23 and Lys26), a pattern found in many I-Ek-binding peptides. TCR reactivity analysis clearly indicates a great variation in the interaction with cl 16-26 by T cells generated from different strains of I-Ek-bearing mice. Most of the T cell generated from A/J mice reacted with the central regions of cl 16-26, while there is a great diversity on the recognition of cl 16-26 by T cells from C3H and B10.BR mice. Despite the diverse interactions with antigenic peptide by these T cells, most TCR-E-k contacts are limited to the central region of the I-Ek beta-chain. T cells recognizing only the N-terminal part of cl 16-26 were found to contact I-Ek at nearly the same residues as T cells interacting with the C-terminal of cl 16-26. TCR-I-Ek recognition was apparently independent of TCR-cl 16-26 contact. The discordant TCR-peptide and TCR-MHC interaction may represent a unique feature of TCR recognition.

A peptide binding weakly to the major histocompatibility molecule augments T cell responses.

An I-A(d)-derived peptide PB1 was found to enhance the reactivity of I-A(d)-restricted T cells. The augmentative effect was not due to the cross-reactivity of PB1 peptide with antigens. PB1 had no effect on T cells specific for I-A(b) and I-E(k), nor did PB1 increase the T cell responses to concanavalin A and staphylococcal enterotoxin B. The strict I-A(d) specificity suggests that PB1 enhances the recognition of antigen-I-A(d) complex by T cell receptor. PB1 bound to I-A(d) weakly. The augmentative effect could be found on other I-A(d)-binding peptides in appropriate conditions; however, PB1 was distinct in its prominently augmentative effect on all the I-A(d)-restricted T cells analyzed. A similar enhancing activity was demonstrated on a synthetic transferrin receptor peptide with minimum affinity for I-A(d). The unusual enhancing activity of PB1 may thus be attributed to the low I-A(d) binding affinity. It was postulated that the binding of low-affinity PB1 would not only stabilize I-A(d) structure, but also enhance the binding of other peptides. This was supported by the increased binding of OVA 323-339 and cI 84-98 to I-A(d) in the presence of PB1. The inclusion of PB1 in the immunization mixture also enhanced T cell responses in vivo, suggesting the possibility of using low-affinity peptide to promote specific immunity.

Iron (III)-chelating resins. 3. Synthesis, iron (III)-chelating properties, and in vitro antibacterial activity of compounds containing 3-hydroxy-2-methyl-4(1H)-pyridinone ligands.

The synthesis, iron (III)-chelating properties, and antibacterial activity of several compounds containing the 3-hydroxy-2-methyl-4(1H)-pyridinone (HMP) moiety are described. Using the HMP derivatives iron (III) could be mobilized from iron (III)-binding proteins at physiological pH with a rate order of transferrin > lactoferrin > ferritin. Addition of HMP-containing compounds to a growth medium at a concentration of 20 mM/L resulted in a complete inhibition of the growth of Escherichia coli and about 90% inhibition for Listeria inocua after 7 h of incubation at 37 degrees C. After inhibition of bacteria growth by the HMP derivatives growth started again when ferric ions were added to the medium, which implies that the antibacterial activity is due to a limitation of iron available to the organisms.

Valve ring abscess associated with infective endocarditis: echocardiographic features and clinical observations.

The presence of a valve ring abscess in patients with infective endocarditis adds appreciably to the expected rates of morbidity and mortality. From January 1989 to October 1991, a total of 43 consecutive patients with infective endocarditis seen at National Taiwan University Hospital were enrolled in this study. There were 30 men and 13 women, ranging in age from 14 to 75 years (mean +/- SD 38.5 +/- 15.0 years). The presence of infective endocarditis was documented by surgery in 26 patients and was based on a clinical diagnosis in the remaining 17 patients. A valve ring abscess was detected in five patients, either by transthoracic or transesophageal echocardiography, and all were confirmed at surgery. Aortic valve endocarditis was more frequently found in patients with valve ring abscesses (100% vs 31.6%, p < 0.01), and the infecting organism was most often Staphylococcus aureus (60.0% vs 15.8%, p < 0.05). The proportion of urgent operations was also higher in the group with abscesses (80.0% vs 23.7%, p < 0.05). The hospital mortality was 40.0% in patients with abscesses and 5.3% in patients without abscesses, but the difference did not reach significance (p = 0.056). Transthoracic echocardiography identified valve ring abscesses in the first three patients, but transesophageal echocardiography was more useful in detecting abscesses located in the posterior aspect of the aortic root in the other two patients, in which the lesion was overlooked or only suspected by the transthoracic approach.(ABSTRACT TRUNCATED AT 250 WORDS)