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At least 1,297 records · Page 72Linked to original sources
PubMed2004

Transcervical carotid stenting with internal carotid artery flow reversal: feasibility and preliminary results.

OBJECTIVE: Transfemoral carotid artery stenting (CAS), with or without distal protection, is associated with risk for cerebral and peripheral embolism and access site complications. To establish cerebral protection before crossing the carotid lesion and to avert transfemoral access complications, the present study was undertaken to evaluate a transcervical approach for CAS with carotid flow reversal for cerebral protection. METHODS: Fifty patients underwent CAS through a transcervical approach. All patients with symptoms had greater than 60% internal carotid artery (ICA) stenosis, and all patients without symptoms had greater than 80% ICA stenosis. Twenty-one patients (42%) had symptomatic disease or ipsilateral stroke, and 8 patients (16%) had contralateral stroke. Four patients (8%) had recurrent stenosis, 7 patients (14%) had contralateral ICA occlusion, and 1 patient (2%) had undergone previous neck radiation. Twenty-seven procedures (54%) were performed with local anesthesia, and 23 (46%) with general anesthesia. Using a cervical cutdown, flow was reversed in the ICA by occluding the common carotid artery and establishing a carotid-jugular vein fistula. Pre-dilation was selective, and 8-mm to 10-mm self-expanding stents were deployed and post-dilated with 5-mm to 6-mm balloons in all cases. RESULTS: The procedure was technically successful in all patients, without significant residual stenoses. No strokes or deaths occurred. There was 1 wound complication (2%). All patients were discharged within 2 days of surgery. Mean flow reversal time was 21.4 minutes (range, 9-50 minutes). Carotid flow reversal was not tolerated in 2 patients (4%). Early in the experience, carotid flow reversal was not possible in 1 patient, and there were 1 major and 3 minor common carotid artery dissections, which resolved after stent placement. One intraoperative transient ischemic attack (2%) occurred in 1 patient in whom carotid flow was not reversed, and 1 patient with a contralateral ICA occlusion had a contralateral transient ischemic attack. At 1 to 12 months of follow-up, all patients remained asymptomatic, and all but 1 stent remained patent. CONCLUSION: Transcervical CAS with carotid flow reversal is feasible and safe. It can be done with the patient under local anesthesia, averts the complications of the transfemoral approach, and eliminates the increased complexity and cost of cerebral protection devices. Transcervical CAS is feasible when the transfemoral route is impossible or contraindicated, and may be the procedure of choice in a subset of patients in whom carotid stenting is indicated.

Aged↗
PubMed2006

Dendritic cell-derived exosomes express a Streptococcus pneumoniae capsular polysaccharide type 14 cross-reactive antigen that induces protective immunoglobulin responses against pneumococcal infection in mice.

Exosomes activate T cells in vivo, but whether exosomes are able to induce humoral immune responses is still unknown. We found that dendritic cells, but not other immune cells, constitutively release an exosome-associated glycoconjugate that is cross-reactive with the capsular polysaccharide of Streptococcus pneumoniae type 14 (Cps14-CRA). Cps14-CRA was localized to the cholesterol-enriched microdomains or rafts of the exosomes and was mapped to the beta1-->6 branched N-acetyl-lactosamine derivatives of the Cps14-CRA. Injection of CFA-primed naive mice with purified dendritic cell exosomes induced immunoglobulin (Ig) anti-Cps14 responses composed predominantly of IgM, IgG3, and IgG1. These responses were associated with protection against a lethal challenge with live S. pneumoniae type 14, but not with type 3 bacteria, and was correlated with the titer of elicited IgM and IgG3 anti-Cps14. These data show, for the first time, that exosomes can induce a humoral immune response to an associated unprocessed, autologous antigen. Although anti-Cps14 Ig responses are specifically demonstrated, these could reflect a broader mechanism that modulates both natural immunity and autoimmunity to other glycotopes.

Animals↗
PubMed2006

Comparative efficacy of subtype AE simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques.

Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.

Animals↗
PubMed1977

Does intermittent coronary perfusion offer greater myocardial protection than continuous aortic cross-clamping?

There has been considerable controversy concerning the relative merits of intermittent coronary perfusion vs. continuous aortic cross-clamping for cardiac procedures requiring ischemic arrest. Using the isovolumic ventricular balloon model and "stop-freeze" biopsy techniques, myocardial contractility (LV dp/dt max, length-tension, and force-velocity relationships) and metabolism (adenine nucleotides, creatine phosphate, and glycogen) were studied in 46 intact dogs supported by normothermic cardiopulmonary bypass and subjected to either 60 minutes of continuous ischemic arrest or to four 15-minute intervals of ischemia each followed by 5 minutes of reperfusion. Following ischemia the hearts were reperfused for 30 minutes and defibrillated after the first 10 minutes. There were no significant differences in either metabolic parameters or contractile function between the groups. Although partial regeneration of adenosine triphosphate and glycogen occurred during reperfusion, only creatine phosphate achieved normal values and the end result was no difference between the two techniques. These data indicate that 5 minutes of coronary reperfusion between consecutive episodes of ischemic arrest affords no greater intraoperative protection of the myocardium than does continuous aortic cross-clamping.

Adenine Nucleotides↗
PubMed2004

Protective efficacy of a DNA influenza virus vaccine is markedly increased by the coadministration of a Schiff base-forming drug.

Effective vaccination against heterologous influenza virus infection remains elusive. Immunization with plasmid DNA (pDNA) expressing conserved genes from influenza virus is a promising approach to achieve cross-variant protection. However, despite having been described for more than a decade, pDNA vaccination still requires further optimization to be applied clinically as a standard vaccination approach. We have recently described a simple and efficient approach to enhance pDNA immunization, based on the use of tucaresol, a Schiff base-forming drug. In this report we have tested the ability of this drug to increase the protection conferred by pDNA vaccination against influenza virus infection. Our results demonstrate that a significant protection was achieved in two strains of mice by using the combination of pDNA and tucaresol. This protection was associated with an elevated humoral and cellular response and a switch in the type of the T helper cell (Th) immune response from type 2 to type 1. This vaccine combination represents a promising strategy for designing a clinical study for the protection from influenza and similar infections.

Adjuvants, Immunologic↗
PubMed2000

Vaccines against bovine mastitis due to Streptococcus uberis current status and future prospects.

The prevalence of bovine mastitis in the UK has been reduced over the past twenty five years due to the implementation of a five-point control plan aimed at reducing exposure, duration and transmission of intramammary infections by bacteria. This has markedly reduced the incidence of bovine mastitis caused by bacteria which show a contagious route of transmission but has had little effect on the incidence of mastitis due to bacteria which infect the gland from an environmental reservoir. Streptococcus uberis is one such bacterium which is responsible for a significant proportion of clinical mastitis worldwide. The inadequacies of the current methods of mastitis control have led to the search for additional measures to prevent intramammary infection by this bacterium. A live vaccine in combination with an intramammary administration of a soluble cell surface extract was shown to induce protection of the mammary gland from experimental challenge with S. uberis. Protection was strain specific, but was achieved in the absence of opsonic activity and without a large influx of neutrophils. One hypothesis is that protection was achieved by reducing the rate of bacterial growth in vivo. This view has led to the identification and exploitation of a novel plasminogen activator as a vaccine antigen. Vaccines containing this antigen conferred cross strain protection.

Animals↗
PubMed1984

Vaccination of calves against Salmonella dublin with aromatic-dependent Salmonella typhimurium.

Ten Holstein calves were divided into 2 groups. Five calves served as nonvaccinated controls, and 5 calves were vaccinated IM at 2 and 3 weeks of age with 10(9) aromatic-dependent (aro-) Salmonella typhimurium strain SL1479 containing O antigens 1, 4, 12. Serious adverse reactions to vaccination were not observed in the calves. Mean maximum rectal temperature increase in the vaccinated calves was 1.5 C. One calf had diarrhea and depressed appetite for 1 day after vaccination. At 5 weeks of age, all calves were challenge exposed orally with 1.5 X 10(11) virulent S dublin strain SL1367 (O antigens 9,12). After challenge-exposure inoculum was given, 1 of 5 vaccinated calves died and 4 of the 5 nonvaccinated calves died (P less than 0.05). Thus, some cross serotype protection against S dublin was induced by parenteral vaccination of calves with aro- S typhimurium strain SL1479, although protection was not complete.

Animals↗
PubMed2002

A new catalytic cross-coupling approach for the synthesis of protected aryl and heteroaryl amidines.

[reaction: see text] A new method for the synthesis of protected benzamidines is described. The commercially available 1,3-bis(tert-butoxycarbonyl)-2-methyl-2-thiopseudourea guanidylation reagent, after SEM-protection, functions as an amidine-forming cross-coupling partner under Liebeskind-Srogl conditions. In the presence of copper(I) thiophenecarboxylate (CuTC), the palladium-catalyzed cross-coupling of the SEM-protected thiopseudourea reagent with boronic acids affords fully protected benzamidines in good to excellent yield (40-91%).

Journal Article↗
PubMed1998

Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA.

DNA vaccination is an effective means of eliciting both humoral and cellular immunity, including cytotoxic T lymphocytes (CTL). Using an influenza virus model, we previously demonstrated that injection of DNA encoding influenza virus nucleoprotein (NP) induced major histocompatibility complex class I-restricted CTL and cross-strain protection from lethal virus challenge in mice (J. B. Ulmer et al., Science 259:1745-1749, 1993). In the present study, we have characterized in more detail the cellular immune responses induced by NP DNA, which included robust lymphoproliferation and Th1-type cytokine secretion (high levels of gamma interferon and interleukin-2 [IL-2], with little IL-4 or IL-10) in response to antigen-specific restimulation of splenocytes in vitro. These responses were mediated by CD4+ T cells, as shown by in vitro depletion of T-cell subsets. Taken together, these results indicate that immunization with NP DNA primes both cytolytic CD8+ T cells and cytokine-secreting CD4+ T cells. Further, we demonstrate by adoptive transfer and in vivo depletion of T-cell subsets that both of these types of T cells act as effectors in protective immunity against influenza virus challenge conferred by NP DNA.

Animals↗
PubMed1986

Cross-reactions in cell mediated immunity induced by atypical mycobacteria.

Cross-reactivity in the delayed hypersensitivity response to mycobacteria of different Runyon groups was tested in Swiss white mice immunised with live mycobacteria. All the strains tested gave cross-reactions and, generally, slow growers gave stronger cross-reactions with other slow growers than with rapid growers and vice versa. Sonicates of cross-reacting mycobacteria were also tested for their ability to generate activated macrophages in mice immunised with Mycobacterium avium. All the mycobacterial sonicates generated activated macrophages but a sonicate of Salmonella typhi did not. The sonicate of M. tuberculosis H37Rv also generated activated macrophages, which indicates that there might be protective cross-reactions between M. tuberculosis and atypical mycobacteria.

Animals↗
PubMed1995

A highly conserved epitope on the spike protein of infectious bronchitis virus.

The predicted amino acid sequence and secondary structures of S1 of the spike protein (S) of infectious bronchitis viral (IBV) strains from Europe, the U.S.A., and Japan were compared. An antigenic determinant that was highly conserved in both the primary amino acid sequence and secondary structure of all strains was identified between amino acid positions 240 to 255. A synthesized peptide corresponding to this region was found to react with all polyclonal antisera examined from various IBV strains and with one monoclonal antibody (MAb), 9B1B6, out of nine known to react with the S of Gray. The specificity of the interaction with MAb 9B1B6 was confirmed by competitive ELISA using bound and unbound peptide. Interestingly, the previously described epitope for 9B1B6 had been characterized as cross-reactive with several strains of IBV, as conformation-independent but reacting only with intact whole S, and as associated with the functional integrity of other epitopes, including neutralizing epitopes on the S protein. The apparent critical functional and structural nature of this highly immunogenic determinant suggests a potential contribution in developing protective, cross-reactive subunit vaccines to IBV.

Amino Acid Sequence↗
PubMed1998

Production and testing of Schistosoma japonicum candidate vaccine antigens in the natural ovine host.

The objectives of this work were to clone and express Chinese strain Schistosoma japonicum antigens and evaluate their immunogenicity and protective efficacy in the natural ovine host in China. Recombinant antigens selected for testing were: isoforms of glutathione S-transferase Sj28GST and Sj26GST; the large hydrophilic domain of Sj23, the homologue of the protective S. mansoni membrane antigen Sm23; and a 3' fragment of S. japonicum paramyosin. In addition, Chinese strain S. japonicum native paramyosin and GST were purified and used for vaccination. Antigens were co-administered with Freund's adjuvants or BCG. We also examined the effects of co-administration of native unfractionated GSTs with keyhole limpet haemocyanin (KLH), which shares a cross-reactive protective epitope with schistosomes. These are the first side-by-side comparisons of candidate defined-antigen schistosomiasis vaccines in a natural host. Significant partial protection was obtained with each of the antigens tested. Less protection was obtained with a recombinant fragment of S. japonicum paramyosin compared with native paramyosin. Co-administration of native GST and KLH was no more effective than vaccination with either antigen alone. Although encouraging levels of protection against S. japonicum were demonstrated using each of these antigens, further work is needed to optimise vaccine delivery and vaccination schedules.

Adjuvants, Immunologic↗
PubMed1998

Heterotypic protection against influenza by immunostimulating complexes is associated with the induction of cross-reactive cytotoxic T lymphocytes.

Influenza immunostimulating complexes (flu-ISCOMs) and a monovalent subvirion vaccine prepared with an H1N1 strain of influenza virus were compared in mice for immunogenicity and protection against challenge with homologous and heterotypic influenza viruses. flu-ISCOMs but not subvirion vaccine fully protected mice against homologous virus challenge after one immunization as assessed by measurement of virus lung titers. The improved protection induced by flu-ISCOMs was associated with a 10-fold higher prechallenge serum hemagglutination inhibition titer. Furthermore, only flu-ISCOMs fully protected mice against mortality and reduced morbidity following challenge with an influenza virus of the serologically distinct H2N2 subtype. This cross-protection correlated with the induction of virus cross-reactive cytotoxic T lymphocytes that recognized a known major histocompatibility class I (H2-Kd)-restricted epitope within the hemagglutinin of influenza virus that is conserved among the H1 and H2 influenza virus subtypes. flu-ISCOMs may offer significant advantages over current commercial formulations as an improved influenza vaccine.

Animals↗
PubMed2006

Protective effects of a mixture of antioxidant vitamins and minerals on the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster.

Antioxidant vitamins are able to deactivate highly bioactive molecules, such as free radicals, that are generated during cellular biochemical processes. Doxorubicin (DXR) is a cancer chemotherapeutic agent that generates free radicals as a byproduct. In the present study, the Drosophila melanogaster somatic wing spot test was used to evaluate the effects of a mixture of vitamins (Vitamins C, E, and beta-carotene) and minerals (copper, selenium, and zinc), commercially known as Vitergan Zinc Plus, on the genotoxicity of DXR in standard and high-bioactivation crosses of flies. 12.5, 25, and 50 mg/ml of the vitamin/mineral mixture by itself was nongenotoxic in the trans-heterozygous descendants of both crosses, while the mixture produced a significant reduction in the genotoxicity produced by 0.125 mg/ml DXR in the trans-heterozygous descendants of both crosses. The protective effect was observed when the larvae received either pre- or cotreatments of the multivitamin/mineral (MV) mixture. The results indicate that, under these experimental conditions, the MV mixture is not genotoxic; however, it protects against the genotoxic effects of the chemotherapeutic free-radical generator DXR.

Animals↗
PubMed1995

Pathogenic, immunologic, and molecular differences between two Ehrlichia risticii strains.

Ehrlichia risticii is the causative agent of Potomac horse fever (PHF), an acute infectious disease of horses. In the last few years, there have been several reports of PHF cases occurring even in vaccinated horses. We isolated a new strain of E. risticii (90-12 strain) from a vaccinated horse suffering from clinical PHF. The major pathogenic, immunologic, and molecular differences between the 90-12 strain and the 25-D stain, which was originally isolated during the outbreaks in 1984, were studied. The 90-12 strain was more pathogenic for mice and horses compared with the 25-D strain. In enzyme-linked immunosorbent assay and immunofluorescence assay with mouse and horse antisera of both the strains, two- to fourfold differences were observed between (immunoblot) with mouse and horse antisera and also with the recombinant clone-specific antibodies. Though several antigens were similar in both the strains, there were significant differences between them in the 110-, 85-, 70-, 51-, and 33-kDa antigens. The 85-kDa antigen was present only in the 90-12 strain but cross-reacted with a 50-kDa antigen of the 25-D strain. The 51-kDa antigens of both strains had different migration patterns, Southern blot hybridization of the genome from both the strains with DNA probes made from the 51-, 55-, and clones for both the strains, whereas the probe of the 85-kDa clone showed a completely different pattern. The 16S rRNA gene sequences from the two strains were identical. Neither strain replicated in gamma interferon-treated mouse peritoneal macrophages. In in vitro neutralization assay, sera from the 25-D strain-infected horse neutralized the homologous strain but did not neutralize the 90-12 strain, whereas sera from the 90-12 strain-infected horse neutralized both the strains. In mouse protection experiments, there was complete homologous protection. But in cross-protection, mice immunized with the 25-D strain were only partially protected against challenge with the 90-12 strain, whereas mice immunized with the 90-12 strain were completely protected against the 25-D strain challenge. These results clearly indicate that there are major differences between the 90-12 and 25-D strains which may have implications regarding the vaccine failure for PHF and the development of an efficient vaccine.

Animals↗
PubMed2002

Immunisation of dairy cattle with recombinant Streptococcus uberis GapC or a chimeric CAMP antigen confers protection against heterologous bacterial challenge.

The gapC genes, encoding the cell surface-associated GapC proteins of S. uberis and S. agalactiae, have been cloned and sequenced. To identify potential vaccine candidates against S. uberis-induced bovine mastitis, lactating dairy cows were vaccinated with either (6 x His)GapC of S. uberis or S. dysgalactiae, or with a chimeric CAMP-factor antigen, CAMP-3. For 7 days following heterologous challenge with S. uberis, milk somatic cell counts were determined to assess differences in the severity of mastitis between vaccinates and an unvaccinated control group. Vaccination with S. uberis (6 x His)GapC or CAMP-3 resulted in a significant reduction in inflammation on several days post-challenge, most significantly for the former antigen. Inflammation was not reduced in S. dysgalactiae (6 x His)GapC vaccinates, suggesting that it does not confer cross-species protection.

Animals↗