MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro

Possession of a properly functioning innate immune system in the lung is vital to prevent infections due to the ongoing exposure of the lung to pathogens. While mechanisms of pulmonary innate immunity have been well studied, our knowledge of how these systems are altered in disease states, leading to increased susceptibility to infections, is limited. One innate immune protein in the lung, the pulmonary collectin SP-D, has been shown to be important in innate immune defense, as well as clearance of allergens and apoptotic cells. MMP-9 is a protease with a wide variety of substrates, and has been found to be dysregulated in a myriad of lung diseases ranging from asthma to cystic fibrosis; in many of these conditions, there are decreased levels of SP-D. Our results indicate that MMP-9 is able to cleave SP-D in vitro and this cleavage leads to loss of its innate immune functions, including its abilities to aggregate bacteria and increase phagocytosis by mouse alveolar macrophages. However, MMP-9-cleaved SP-D was still detected in a solid-phase E. coli LPS-binding assay, while NE-cleaved SP-D was not. In addition, MMP-9 seems to cleave SP-D much more efficiently than NE at physiological levels of calcium. Previous studies have shown that in several diseases, including cystic fibrosis and asthma, patients have increased expression of MMP-9 in the lungs as well as decreased levels of intact SP-D. As patients suffering from many of the diseases in which MMP-9 is over-expressed can be more susceptible to pulmonary infections, it is possible that MMP-9 cleavage of SP-D may contribute to this phenotype

Proximal Gastrojejunal Reconstruction after Pancreaticoduodenal Resection

Introduction. Reconstruction by proximal gastrojejunostomy, and distal biliary and pancreatic anastomoses is infrequently used after resection of the head of the pancreas because of fear of fistulas and cholangitis. Pancreaticoduodenectomy is being performed more frequently for cystic malignant and premalignant lesions. Because of this there is a need for endoscopic visualization and biopsy of the residual pancreatic duct, since multi-centricity is characteristic of some of these malignancies. Since endoscopic access of the bile duct and pancreatic duct is difficult and unsuccessful in 50–70% after B II or Roux Y reconstruction, we prospectively studied the merit and complications (early and late) of proximal gastrojejunal (PGJ) reconstruction after pancreaticoduodenal resection. Material and Methods. Thirty nine consecutive, non-radomized patients underwent pancreaticoduodenectomy and PGJ reconstruction over 14 mos. There were 21 males and 18 females. Results. 7 patients with IPMN have undergone repeat CT scanning for surveillance, with 3 requiring repeat EUS and ERCP. There were no technical difficulties accessing the pancreas or the pancreatic duct, supporting the PGJ reconstruction. Conclusion. Proximal gastrojejunal reconstruction following pancreaticoduodenal resection may be safely done with similar morbidity to traditional pancreaticojejunal reconstructions. PGJ reconstruction may be of greater value when direct visual access to the bile duct or pancreatic duct is necessary, and should be considered when doing resection for mucinous cysts or IPMN of the head of the pancreas

Revealing the structure of the outer disks of Be stars

Context. The structure of the inner parts of Be star disks (20 stellar radii) is well explained by the viscous decretion disk (VDD) model, which is able to reproduce the observable properties of most of the objects studied so far. The outer parts, on the ther hand, are not observationally well-explored, as they are observable only at radio wavelengths. A steepening of the spectral slope somewhere between infrared and radio wavelengths was reported for several Be stars that were previously detected in the radio, but a convincing physical explanation for this trend has not yet been provided. Aims. We test the VDD model predictions for the extended parts of a sample of six Be disks that have been observed in the radio to address the question of whether the observed turndown in the spectral energy distribution (SED) can be explained in the framework of the VDD model, including recent theoretical development for truncated Be disks in binary systems. Methods. We combine new multi-wavelength radio observations from the Karl. G. Jansky Very Large Array (JVLA) and Atacama Pathfinder Experiment (APEX) with previously published radio data and archival SED measurements at ultraviolet, visual, and infrared wavelengths. The density structure of the disks, including their outer parts, is constrained by radiative transfer modeling of the observed spectrum using VDD model predictions. In the VDD model we include the presumed effects of possible tidal influence from faint binary companions. Results. For 5 out of 6 studied stars, the observed SED shows strong signs of SED turndown between far-IR and radio wavelengths. A VDD model that extends to large distances closely reproduces the observed SEDs up to far IR wavelengths, but fails to reproduce the radio SED. ... (abstract continues but did not fit here)Comment: 20 pages, 8 figure

The Influence of IS1301 in the Capsule Biosynthesis Locus on Meningococcal Carriage and Disease

Previously we have shown that insertion of IS1301 in the sia/ctr intergenic region (IGR) of serogroup C Neisseria meningitidis (MenC) isolates from Spain confers increased resistance against complement-mediated killing. Here we investigate the significance of IS1301 in the same location in N. meningitidis isolates from the UK. PCR and sequencing was used to screen a collection of more than 1500 meningococcal carriage and disease isolates from the UK for the presence of IS1301 in the IGR. IS1301 was not identified in the IGR among vaccine failure strains but was frequently found in serogroup B isolates (MenB) from clonal complex 269 (cc269). Almost all IS1301 insertions in cc269 were associated with novel polymorphisms, and did not change capsule expression or resistance to human complement. After excluding sequence types (STs) distant from the central genotype within cc269, there was no significant difference for the presence of IS1301 in the IGR of carriage isolates compared to disease isolates. Isolates with insertion of IS1301 in the IGR are not responsible for MenC disease in UK vaccine failures. Novel polymorphisms associated with IS1301 in the IGR of UK MenB isolates do not lead to the resistance phenotype seen for IS1301 in the IGR of MenC isolates

Frequent capsule switching in 'ultra-virulent' meningococci - Are we ready for a serogroup B ST-11 complex outbreak?

The meningococcal ST-11 complex (cc11) causes large invasive disease outbreaks with high case fatality rates, such as serogroup C (MenC) epidemics in industrialised nations in the 1990s and the serogroup W epidemic currently expanding globally. Glycoconjugate vaccines are available for serogroups A, C, W and Y. Broad coverage protein-based vaccines have recently been licensed against serogroup B meningococci (MenB), however, these do not afford universal MenB protection. Capsular switching from MenC to MenB among cc11 organisms is concerning because a large MenB cc11 (B:cc11) outbreak has the potential to cause significant morbidity and mortality. This study aimed to assess the potential for licensed and developmental non-capsular meningococcal vaccines to protect against B:cc11. The population structure and vaccine antigen distribution was determined for a panel of >800 geo-temporally diverse, predominantly MenC cc11 and B:cc11 genomes. The two licensed vaccines potentially protect against many but not all B:cc11 meningococci. Furthermore, strain coverage by these vaccines is often due to a single vaccine antigen and both vaccines are highly susceptible to vaccine escape owing to the apparent dispensability of key proteins used as vaccine antigens. cc11 strains with MenB and MenC capsules warrant special consideration when formulating future non-capsular meningococcal vaccines

Clonal expansion of new penicillin-resistant clade of neisseria meningitidis serogroup w clonal complex 11, Australia

In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease

Differential expression of collectins in human placenta and role in inflammation during spontaneous Labor.

© 2014 Yadav et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Collectins, collagen-containing Ca2+ dependent C-type lectins and a class of secretory proteins including SP-A, SP-D and MBL, are integral to immunomodulation and innate immune defense. In the present study, we aimed to investigate their placental transcript synthesis, labor associated differential expression and localization at feto-maternal interface, and their functional implication in spontaneous labor. The study involved using feto-maternal interface (placental/decidual tissues) from two groups of healthy pregnant women at term (≥37 weeks of gestation), undergoing either elective C-section with no labor ('NLc' group, n = 5), or normal vaginal delivery with spontaneous labor ('SLv' group, n = 5). The immune function of SP-D, on term placental explants, was analyzed for cytokine profile using multiplexed cytokine array. SP-A, SP-D and MBL transcripts were observed in the term placenta. The 'SLv' group showed significant up-regulation of SP-D (p = 0.001), and down-regulation of SP-A (p = 0.005), transcripts and protein compared to the 'NLc' group. Significant increase in 43 kDa and 50 kDa SP-D forms in placental and decidual tissues was associated with the spontaneous labor (p<0.05). In addition, the MMP-9-cleaved form of SP-D (25 kDa) was significantly higher in the placentae of 'SLv' group compared to the 'NLc' group (p = 0.002). Labor associated cytokines IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α and MCP-1 showed significant increase (p<0.05) in a dose dependent manner in the placental explants treated with nSP-D and rhSP-D. In conclusion, the study emphasizes that SP-A and SP-D proteins associate with the spontaneous labor and SP-D plausibly contributes to the pro-inflammatory immune milieu of feto-maternal tissues.Funding provided by BT/PR15227/BRB/10/906/2011) Department of Biotechnology (DBT), Government of India http://dbtindia.nic.in/index.asp (TM) and Indian Council of Medical Research (ICMR) Junior Research Fellowship (JRF)/Senior Research Fellowship (SRF), Government of India, www.icmr.nic.in (AKY)

The Vehicle, 1967, Vol. 9 no. 2

Table of Contents Commentarypage 3 SketchAnn Butlerpage 4 I Take A Long-Out-of-Use BookAnthony Griggspage 5 The Leaf StemDianne Cochranpage 6 The Four MusketeersJim Courterpage 7 Status QuoAdrian Beardpage 7 SketchAnn Butlerpage 8 NocturneMike Baldwinpage 9 Oh Impatient HeartK. H. Shariffpage 9 Letter to a FianceeMaurice Snivelypage 10 Listen!Bonnie Blackpage 11 The Water\u27s EdgeStephen W. Gibbspage 12 TogetherDavid Reifpage 13 SketchAnn Butlerpage 14 Evening TimeSharon Nelsonpage 15 Japanese HaikuBev Hensonpage 15 Of Love and WarBruce Czeluscinskipage 16 Always AloneKib Voorheespage 17 the end of loveJackie Bratcherpage 18 1-20-66Sharon Nelsonpage 19 Blessed Are WeBonnie Marie Beckpage 19 The Time To LiveNeil Tracypage 20 Imminent AwakeningHelen Coxpage 21 The Dead Panther LairMolly J. Evanspage 21 Good SheepMike Tilfordpage 22 The Flame of LifeJacki Jacquespage 23 Then Arrives The Day Of DarkMolly J. Evanspage 23 Sketch: To love is to rememberAnn Butlerpage 24 Hidden RiversCharles J. Mertzpage 25 SilenceLinda G. Phillipspage 26 December - 1964Bonnie Blackpage 26 LoveHazel Thomaspage 27 To Praise A Good Man Neil Tracypage 28 Definitions \u2767Sharon Nelsonpage 29 To Wish Is a CrimeBonnie Marie Beckpage 30 College MadhatterMaurice Snivelypage 31 No. 8Sharon Nelsonpage 32 The Open FireSusan Williamspage 32https://thekeep.eiu.edu/vehicle/1017/thumbnail.jp