Evaluation of a virus derived from MDCK cells infected persistently with influenza A virus as a potential live-attenuated vaccine candidate in the mouse model

A temperature-sensitive mutant virus unable to replicate at 38 degrees C was recovered from passage 189 (IVpi-189) of Madin-Darby canine kidney cells infected persistently with influenza A. Immunofluorescent staining of the IVpi-189 virus-infected cells revealed disrupted transport of the matrix (M) 1 protein into the nucleus at non-permissive temperatures, resulting in retention of the nucleoprotein (NP) in the nucleus. Upon comparison with the parental influenza A E61-24-P15 strain used to establish persistent infection, amino acid exchanges were found in the M1 protein of IVpi-189 virus; arginine to glutamine at position 72 and threonine to alanine at position 139. When mice were inoculated intranasally with IVpi-189 virus, virus growth in the lungs was restrained and terminated rapidly. Prior intranasal inoculation with only a small dose of IVpi-189 virus induced humoral and cellular immune responses and protected mice against subsequent virulent virus challenge. These results indicate that IVpi-189 virus, an avirulent temperature-sensitive mutant, is a promising candidate for use as a live-attenuated vaccine.     

Th17 cells in inflammation and autoimmunity

T helper 17 (Th17), a distinct subset of CD4⁺ T cells with IL-17 as their major cytokine, orchestrate the pathogenesis of inflammatory and autoimmune diseases. Dysregulated Th17 cells contribute to inflammatory and autoimmune diseases. Candidate biologics are in development for targeting IL-17, IL-17 receptors or IL-17 pathways. Several drugs that impact the IL-17 pathway are already in clinical trials for the treatment of autoimmune diseases. In this review we provide evidence for the role of Th17 cells in immune-mediated diseases. An understanding of the role of Th17 in these conditions will provide important insights and unravel novel targets for therapeutic intervention.     

Accuracy of transcutaneous bilirubinometry in the preterm infants: a comprehensive meta-analysis

Background: Transcutaneous bilirubin (TcB) measurement is widely used in term babies. But its effectiveness till debated in preterm infants. So, our objective was to pool data to see the accuracy of transcutaneous bilirubinometry in preterm infants.

Method: MEDLINE, Embase, Cochrane Library database were searched from 2000 to July 2017. The included studies had compared TcB with total serum bilirubin (TSB) in preterm infants before phototherapy and data were presented as correlation coefficients. Data were extracted by two reviewers and checked for accuracy by the third reviewer. The risk bias assessments were done by an assessment quality assessment of diagnostic accuracy studies tool. Pooled correlation coefficient assed after Fisher’s z transformation and then converted to r.

Results: We included 28 studies; all those studies reported results as correlation coefficients. In combination of both sternal and forehead site measurement, our pooled estimates of r?=?0.82 (95% CI: 0.78–0.85) in random effect and r?=?0.803 (95% CI: 0.78–0.81) in fixed effect model. For separate sites of measurement of TcB pooled r for forehead and sternum were comparable, r?=?0.82 (95% CI: 0.78–0.85), and pooled correlation coefficient for the two devices JM103 and Bilicheck the estimated pooled r were also comparable (Pooled r?=?0.83).

Conclusion: Our study found that TcB measurement is well related with TSB values and can represent a reliable method for evaluating preterm infants with possible hyperbilirubinemia. Our findings support the use of investigated devices at both forehead and sternum sites in preterm infants.     

Serum immunoglobulin G, M and IgG:IgM ratio as predictors for outcome of childhood nephrotic syndrome

Background  Nephrotic syndrome is an immune mediated disorder of the kidney associated with T cell dysfunction and secondary disturbance of B cell with changes in levels of immunoglobulin and IgG:IgM ratio. These changes in immunoglobulin levels can be used as a proxy marker to understand the clinical variety and prognosis of nephrotic syndrome. Methods  We studied 43 children with nephrotic syndrome during January 2003 to January 2005 in the Pediatric Nephrology Unit, Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Blood samples were collected from the 43 patients, and serum levels of IgG, IgM and IgG:IgM were measured by liquid phase immunoprecipitation assay. Another 20 healthy children attending the laboratory for blood grouping and hepatitis B screening test were enrolled as controls. Results  In the 43 children with nephrotic syndrome, 24 had steroid sensitive nephrotic syndrome (SSNS) and 19 steroid resistant nephrotic syndrome (SRNS). Compared with healthy children, the IgG level was low, IgM level was high, and IgG:IgM ratio was low (P<0.05). The serum IgG level and IgG:IgM ratio were significantly lower in children with SRNS and in children with frequent relapse (FRNS) combined with steroid dependent nephrotic syndrome (SDNS) than in those with infrequent relapse nephrotic syndrome (IFRNS) (P<0.05, respectively). Conclusions  Management of different nephrotic syndromes is based on the levels of immunoglobulins along with clinical and biochemical parameters. The decrease of IgG level as a predictive marker for unfavorable prognosis of nephrotic syndrome in children needs further evaluation in larger scale studies.     

Manubriosternal subluxation/dislocation can lead to manubriosternal septic arthritis in patients with kyphoscoliosis

Locally deranged joint anatomy can predispose to septic arthritis which can be managed by surgical debridement. We present a case of manubriosternal subluxation/dislocation caused by kyphoscoliosis leading to manubriosternal septic arthritis.     

Midterm Assessment of Causes and Results of Revision Total Knee Arthroplasty

Background  

There is limited information regarding revision total knee arthroplasty (TKA) with respect to etiology, outcome, and long-term survival comparing different implant types.     

Enumeration of Gut-Homing β7-Positive,Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients,Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique

Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates β7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. β7 is a cell surface marker associated with mucosal homing. We isolated β7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination.     

Redox-linked signal transduction pathways for protein tyrosine kinase activation

The signaling for activation of protein tyrosine kinases (PTKs) is usually started by binding of ligands to cell-surface receptors. However, recent evidence suggests the presence of ligand binding-independent signaling pathways that are mediated by oxidative stress. Oxidation and reduction of protein cysteine sulfhydryl (SH) groups may work as a molecular switch to start or to stop the signaling. It is known that oxidation of cysteine SH groups on protein tyrosine phosphatases switches off the action of protein tyrosine phosphatases. This event may not, however, signal for initial autophosphorylation of previously unphosphorylated PTKs, whereas it certainly prevents dephosphorylation of once-phosphorylated PTKs. We have suggested new mechanisms for oxidative stress-mediated PTK activation. First, cell-surface glycosylphosphatidylinositol-anchoring proteins and a phosphoglycolipid/cholesterol-enriched membrane microdomain termed a "raft" can be the direct targets of oxidative stress for inducing their clustering through an S-S-bonded or S-X-S-bonded crosslinking of cell-surface proteins and subsequent activation of raft-associating Src family PTKs. Second, intracellular specific cysteine SH groups on PTK proteins can be another target of oxidative stress for inducing a conformational change necessary for initial activation of PTKs. A possible relationship between cell-surface and intracellular events is that the former frequently induces superoxide production as the second messenger for the latter.