Colonization of the gut by virulent Vibrio cholerae is suppressed by probiotic-like activity of a live cholera vaccine candidate and Lactococcus lactis in two animal models (Hubbard et al. and Mao et al. , this issue).

Background. No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model.Methods. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 x 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 x 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration.Results. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (>= 3.0 L) to severe (>= 5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P<.0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P<.0001).Conclusions. The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine.

Orally-administered cholera vaccine (OCV) has been increasingly examined as an additional tool to intervene against endemic and epidemic cholera. In 2013, short- and long-term field experience with OCV under nine distinctive field settings was reported from India, Bangladesh, Vietnam, Guinea, Haiti, and Thailand. Lead investigators from each of these projects presented their findings at a symposium chaired by Drs. David A. Sack and Robert H. Hall at the Vaccines for Enteric Diseases (VED) Conference in Bangkok on November 7, 2013. The objective of the symposium was to describe the unique features of each setting and project, share field experience of implementing cholera vaccination, discuss results, and identify constraints to the wider use of OCV. The VED provided a forum where >200 attendees engaged with this exciting and potentially decisive new development in the cholera field.

Important biomedical information is often recorded, published or archived in unstructured and semi-structured textual form. Artificial intelligence and knowledge discovery techniques may be applied to large volumes of such data to identify and extract useful metadata, not only for providing access to these documents, but also for conducting analyses and uncovering patterns and trends in a field. The System for Preservation of Electronic Resources (SPER), an information management tool developed at the U.S. National Library of Medicine, provides these capabilities by integrating machine learning, data mining and digital preservation techniques. In this paper, we present an overview of SPER and its ability to retrieve information from one such dataset. We show how SPER was applied to the semi-structured records of an international health science program, the 46-year continuous archive of conference publications and related documents from the Joint Cholera Panel of the U.S.-Japan Cooperative Medical Science Program (CMSP). We explain the techniques by which metadata was extracted automatically from the semi-structured document contents to preserve these publications, and show how such data was used to quantitatively describe the activity of a research community toward a preliminary study of a subset of its specific health science program goals.

Rapid- and step-scan photoacoustic (PA) infrared spectra of three fractions of a Syncrude post-extraction oil sand were analyzed in detail in this work. The rapid-scan spectra showed that the samples were comprised primarily of kaolinite, quartz, silica, siderite, and residual hydrocarbons, and that the proportions of these constituents were different for each fraction. Depth profiling of the three post-extraction oil sands was accomplished using both rapid- and step-scan PA infrared spectroscopy. The results confirmed that kaolinite is more abundant in the near-surface region, whereas quartz and hydrocarbons are concentrated at greater depths. The modulation frequency dependence of the PA intensities for all three fractions was consistent with a model in which the samples are thermally thick; in other words, the thermal diffusion length (roughly equal to the sampling depth) was less than the particle sizes of all three samples. The results of this study are consistent with published reports on the PA infrared spectra of fine tailings generated during bitumen extraction and the spectroscopic and thermophysical characterization of clay soils and an appropriate model clay.

Diarrheal diseases remain a major cause of death in children under 5 in less developed countries (LDCs). Vaccine development and implementation offers the best near-term approach to alleviating this problem. For this reason, a workshop to examine the possibilities for making enteric vaccines available to meet the specific needs of children in LDCs was convened in Virginia on April 24-26, 2004. Discussants considered research and development needs, regulatory and business issues, and previous experiences with enteric vaccine development and implementation. No insurmountable roadblocks to progress in this area were noted, and the possibility currently exists that properly supported efforts will enable the realization of enteric vaccines for pediatric use.

UNLABELLED:When opioids are used for postoperative pain control, it is useful to define the dose-response relationship for analgesia and respiratory depression. We studied 20 chronically opioid-consuming patients having elective multilevel spine fusion. Preoperatively, each patient received a fentanyl infusion of 2 microg x kg(-1) x min(-1) until the respiratory rate was <5 breaths/min. Pharmacokinetic simulations were used to estimate the effect site concentration at the time of respiratory depression and to predict the patient-controlled analgesia settings that would provide an effect-site fentanyl concentration that was 30% of the concentration associated with respiratory depression. Postoperatively, patient-controlled analgesia settings were adjusted to achieve 2-3 demand doses per hour. At steady-state patient-controlled analgesia settings, arterial blood gases and plasma fentanyl levels were measured. Sixteen patients required no adjustment or one patient-controlled analgesia adjustment. The median arterial Pco(2) level was 41 mm Hg and the interquartile range was 39-46 mm Hg. Plasma fentanyl levels demonstrated a significant correlation to the estimated effect-site concentration associated with respiratory depression determined during the preoperative fentanyl challenge. A preoperative fentanyl challenge used with pharmacokinetic simulations may be a useful tool to individualize the administration of analgesics to chronically opioid-consuming patients. IMPLICATIONS:In chronically opioid-consuming patients, doses causing respiratory depression and analgesia may differ from those in opioid-naive individuals. A preoperative infusion of fentanyl, used in conjunction with pharmacokinetic simulation, may be a valuable tool for identifying clinical end-points, such as respiratory depression and analgesia, and individualizing postoperative treatment of pain in patients who chronically consume opioids.

Raman, photoacoustic infrared, and UV/visible/near-infrared absorption spectra of six Syncrude Sweet Blend distillation fractions with boiling point ranges that span the 160-250degreesC temperature interval are described in this article. Both FT-Raman and dispersive Raman spectra of the fractions contain a large number of bands, the majority being due to aliphatic groups. Other Raman features are attributable to aromatic species; the dependence of the bands that arise from monocyclic or bicyclic aromatics on boiling temperature was studied and the monocyclic/bicyclic ratio was calculated for each sample. The Raman and infrared spectra show that the proportions of aliphatic (CH, CH2 and CH) groups are approximately constant for the six fractions. The near-UVand near-infrared spectra exhibit several bands that vary systematically with boiling point, creating additional possibilities for the quantitation of aromatics and the prediction of boiling points of unknown samples.

A sensitive and specific PCR-ELISA was developed to detect Escherichia coli O157:H7 and other Shiga toxin-producing E. coli (STEC) in food. The assay was based on the incorporation of digoxigenin-labeled dUTP and a biotin-labeled primer specific for Shiga toxin genes during PCR amplification. The labeled PCR products were bound to streptavidin-coated wells of a microtiter plate and detected by an ELISA. The specificity of the PCR was determined using 39 bacterial strains, including STEC, enteropathogenic E. coli, E. coli K12, and Salmonella. All of the STEC strains were positive, and non-STEC organisms were negative. The ELISA detecting system was able to increase the sensitivity of the PCR assay by up to 100-fold, compared with a conventional gel electrophoresis. The detection limit of the PCR-ELISA was 0.1-10 CFU dependent upon STEC serotypes, and genotypes of Shiga toxins. With the aid of a simple DNA extraction system, PrepMan, the PCR-ELISA was able to detect ca. 10(5) CFU of STEC per gram of ground beef without any culture enrichment. The entire procedure took about 6 h. Because of its microtiter plate format, PCR-ELISA is particularly suitable for large-scale screening and compatible with future automation.

A potent toxin with phospholipase A 2 (PLA 2 ) and hemolytic activity in vitro was purified from the Russell's viper venom of eastern India (RVV-EI). The purified protein (RVV-PFIIc′) of 15.3 kDa molecular weight, and a lethal toxicity dose (LD 50 i.p.) of 0.1 mg/kg body weight, was the most toxic PLA 2 so far reported from the Indian subcontinent. The material also possessed anticoagulant activity as it enhanced the prothrombin induced plasma clotting time in vitro . The PLA 2 toxin (RVV-PFIIc′) was shown to be different from other PLA 2 s of RVV in respect to one or more of these parameters e.g. molecular weight, isoelectric pH, in vivo toxicity, specific activity of the enzyme and certain other biological activities. The first 19 amino terminal sequence (NLFQFAEMIVKMTGKEAVH) of RVV-PFIIc′ showed variable degree of homology (42.1–94.7%) with those of other RVV-PLA 2 s described in the literature. Antisera raised against RVV-EI or RVV-PFIIc′, though completely neutralized the in vivo lethal toxicity of RVV-EI or RVV-PFIIc′, failed to inhibit their PLA 2 activity in vitro thereby suggesting that in vivo toxicity and in vitro activity of the enzyme may not be directly related. Apart from RVV-PFIIc′, at least two other PLA 2 isozymes were found to be present in RVV-EI that were distinct from RVV-PFIIc′ in respect to their molecular, biological as well as serological properties. The significance of these and related data in antivenom therapy is discussed.

Adherence to HEp-2 cells by many enteroaggregative Escherichia coli (EAggEC) strains is associated with the expression of flexible, bundle-forming fimbriae 2 to 3 nm in diameter, designated aggregative adherence fimbriae I (AAF/I). We have previously reported the molecular cloning and TnphoA mutagenesis of AAF/I genes from the large plasmid of prototype EAggEC strain 17-2 (J. P. Nataro, Y. Deng, D. R. Maneval, A. L. German, W. C. Martin, and M. M. Levine, Infect. Immun. 60:2297-2304, 1992). Here, we report that further mapping and subcloning of AAF/I regions suggest that expression of the fimbriae requires two separate plasmid regions (designated regions 1 and 2). Approximately 9 kb of DNA unnecessary for fimbrial expression separates the two regions; this intervening segment encodes the EAggEC heat-stable enterotoxin (EAST1). Neither region was capable of conferring aggregative HEp-2 adherence (AA) when cloned individually; when the two regions were cloned as a single fragment or when each was cloned into a different vector and introduced into the same E. coli HB101 cell, AA was restored. AA-positive constructs also expressed human erythrocyte hemagglutination, autoagglutination in broth cultures, and the production of AAF/I as detected by immunogold electron microscopy.

The infant mouse cholera model has been used to evaluate the relative importance of toxin-coregulated pili (TCP) as protective antigens of Vibrio cholerae 01. Electron microscopic and immunoblotting analyses revealed that, under the cultural conditions examined, TCP were only expressed by strains of classical biotype. Antibodies to TCP were sufficient to confer protection against two such strains, and were more efficient if the challenge vibrios were cultured for TCP expression. In contrast, such antibodies did not protect mice against challenge with any of four strains of El Tor biotype. Since two of the latter have previously been shown to possess non-lipopolysaccharide protective antigens, these results suggest that TCP are not the only such antigen in this model.

Colonization of the small intestine is an essential step in the pathogenesis of Vibrio cholerae diarrhea. At least one type of fimbriae, known as TcpA are required for the colonization process. This paper reports electron microscopic evidence that V. cholerae strains can express at least two other fimbrial types. Classical strains express three types: TcpA fimbriae are 5–6 nm in diameter and form bundles of parallel undulating filaments up to 15 μm long; Type B are 3 nm wide and of wavy morphology, and Type C are rigid, isolated filaments 5–6 nm wide and 180–800 nm long. El Tor strains express fimbriae resembling Types B and C. Types B and C were also found on a tcpA− isogenic mutant of V. cholerae 395 N1, and are thus encoded by genetically distinct loci. TcpA fimbriae, but not Types B or C, were labeled with gold-conjugated anti-TcpA antibody. Four El Tor strains, including two environmental isolates that poorly colonize humans, expressed fimbriae resembling Types B and C, but did not express TcpA. Multiple types of fimbriae may represent colonization factors for surfaces present in the environment and in the human gut. Characterization of the role of fimbriae in immunogen presentation and immunity could facilitate the improvement of cholera vaccines.

Conference Article| February 01 1986 The effects of Vibrio cholerae haemolysin on cation transport in human erythrocytes ROBERT H. HALL; ROBERT H. HALL *Department of Medical Microbiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, U.K. Search for other works by this author on: This Site PubMed Google Scholar ANDREW C. HALL; ANDREW C. HALL ‡ †Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, U.K. ‡To whom correspondence should be addressed Search for other works by this author on: This Site PubMed Google Scholar J. CLIVE ELLORY J. CLIVE ELLORY †Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1986) 14 (1): 120–121. https://doi.org/10.1042/bst0140120 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation ROBERT H. HALL, ANDREW C. HALL, J. CLIVE ELLORY; The effects of Vibrio cholerae haemolysin on cation transport in human erythrocytes. Biochem Soc Trans 1 February 1986; 14 (1): 120–121. doi: https://doi.org/10.1042/bst0140120 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: HU, haemolytic unit This content is only available as a PDF. © 1986 Biochemical Society1986 Article PDF first page preview Close Modal You do not currently have access to this content.