Protect yourself and patients at chairside from cross-contamination.
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A bacterial strain, tentatively identified as an Actinobacillus species, was found to asymptomatically colonize the pharynx of some rats and to bear cell wall antigens which cross-react with noncapsular antigens of Haemophilus influenzae type b (HIb). The cross-reacting antigens appeared to be a heterogeneous mixture with varying molecular size and charge. The antigenic moieties are probably carbohydrate in nature. Antisera raised with this strain had both immunochemical and biological (bactericidal, opsonizing, and protective against experimental infection) activity against HIb. These findings lend further evidence to the idea that noncapsular antigens are important in the induction of resistance to HIb disease. The findings also raise the possibility of using bacteria which cross-react with noncapsular antigens for immunization against HIb disease in humans through nasopharyngeal or enteric colonization.
UNLABELLED: We conducted a randomized, controlled, cross-over cadaver study to test the hypothesis that the efficacy of seal for ventilation and airway protection, anatomic position, and airway patency with the flexible laryngeal mask airway (FLMA) are altered by the application of a Boyle Davis (B-D) gag. We also determined the airway sealing pressure (ASP) at which the FLMA prevents aspiration when large volumes of fluid are placed above the cuff. We studied 20 adult cadavers (6-24 h postmortem). Efficacy of seal for ventilation and airway protection, anatomic position, and airway patency were determined with and without a B-D gag (two blade sizes: 8 and 10 cm) for the size 3, 4, and 5 FLMA in random order. Efficacy of seal for ventilation was determined by measuring the ASP at an intracuff pressure of 60 cm H2O. Efficacy of seal for airway protection was determined by flooding the mouth with 55-135 mL of water, reducing intracuff pressure until aspiration was detected fiberoptically and measuring ASP at this intracuff pressure. Anatomic position and airway patency were determined with a fiberoptic scope at an intracuff pressure of 60 cm H2O. In addition, in vivo compliance and ASP for the FLMA were measured in 10 cadavers and 10 paralyzed, anesthetized patients. Efficacy of seal for ventilation and airway protection, anatomic position, and airway patency did not change with the application of a gag for any mask size. The mean (range) ASP at which aspiration occurred when large volumes of fluid were placed above the cuff was 11 (7-15) cm H2O. The ASP for ventilation was always higher than the ASP for airway protection (P<0.0001). The FLMA had similar in vivo compliance and ASP in cadavers and anesthetized patients. We conclude that efficacy of seal for ventilation and airway protection, anatomic position and airway patency for the FLMA are unaffected by the application of a B-D gag in adults. ASP should be >15 cm H2O if there is a maximal risk of aspiration from above the cuff. IMPLICATIONS: The flexible laryngeal mask airway forms an effective seal for ventilation and protection of the airway that is unaffected by the application of a mouth gag that provides surgical access to the oropharynx. The efficacy of the seal should be >15 cm H2O if there is a maximal risk of aspiration from above the cuff.
This study characterized exposure for dust-producing construction tasks. Eight common construction tasks were evaluated for quartz and respirable dust exposure by collecting 113 personal task period samples for cleanup; demolition with handheld tools; concrete cutting; concrete mixing; tuck-point grinding; surface grinding; sacking and patching concrete; and concrete floor sanding using both time-integrating filter samples and direct-reading respirable dust monitors. The geometric mean quartz concentration was 0.10 mg/m(3) (geometric standard deviation [GSD]=4.88) for all run time samples, with 71% exceeding the threshold limit value. Activities with the highest exposures were surface grinding, tuck-point grinding, and concrete demolition (GM[GSD] of 0.63[4.12], 0.22[1.94], and 0.10[2.60], respectively). Factors recorded each minute were task, tool, work area, respiratory protection and controls used, estimated cross draft, and whether anyone nearby was making dust. Factors important to exposure included tool used, work area configuration, controls employed, cross draft, and in some cases nearby dust. More protective respirators were employed as quartz concentration increased, although respiratory protection was found to be inadequate for 42% of exposures. Controls were employed for only 12% of samples. Exposures were reduced with three controls: box fan for surface grinding and floor sanding, and vacuum/shroud for surface grinding, with reductions of 57, 50, and 71%, respectively. Exposures were higher for sweeping compound, box fan for cleanup, ducted fan dilution, and wetted substrate. Construction masons and laborers are frequently overexposed to silica. The usual protection method, respirators, was not always adequate, and engineering control use was infrequent and often ineffective.
There is clear evidence that BCG protects against leprosy, but cross-immunity with environmental mycobacteria can interfere with vaccination protection. Some have cast doubts whether BCG vaccination can offer a significant impact against leprosy in the Brazilian Amazon, which is an endemic area for leprosy and with a high prevalence of environmental mycobacteria. This study was designed to estimate the vaccine effectiveness of neonatal BCG against leprosy in Amazon region, in Brazil. This is a cohort study nested in a randomized community trial. The study had two main results. First, neonatal BCG vaccination in Brazilian Amazon elicited protection of 74% (95% CI 57-86) against all forms of leprosy cases. Second, the highest protection was observed for multibacillary cases, 93% (95% CI 71-98). It is concluded that the study provides evidence that neonatal BCG may have an important and overlooked impact on the occurrence and transmission of leprosy, maybe even more in the future when the cohort which received a high coverage of BCG reaches the age of high incidence of leprosy.
Sequential inoculations of chickens with different live infectious bronchitis virus (IBV) antigenic types had major effects on virus-neutralization (VN) and hemagglutination-inhibition (HI) serum antibody responses. Antibody production in IBV-inoculated chickens that were reinoculated 8 weeks later with heterologous virus was largely directed against the virus used for initial inoculation rather than the virus used for reinoculation. In addition, chickens inoculated sequentially with IBV produced a broadened spectrum of serum antibodies that reacted with IBV types to which the birds had never been exposed (JMK and Florida). Chickens inoculated sequentially with heterologous IBV tended to produce higher levels of cross-reacting antibody than birds given homologous virus inoculations. Levels of cross-reacting antibodies were lower than levels of specific antibodies directed against viruses that the birds had received. Limited studies indicated that birds with cross-reacting antibodies were not protected against challenge with the virus that the cross-reacting antibody was directed against. Implications of the research for interpreting serological data from commercial chicken flocks are discussed.
The advantages and limitations of cardioplegia as a mode of myocardial preservation in the pediatric cardiac surgical context are investigated. Review of early mortality related to ischemic time demonstrated no difference in overall mortality in consecutive series each of 200 patients, the first protected by reperfusion between intermittent periods of aortic cross-clamping and the second protected by cardioplegia. There was a tendency to accept longer ischemic time with cardioplegia (p less than 0.01). Mortality with cardioplegia increased sharply beyond 85 minutes of ischemia. Cytochemical and biophysical assessment of 129 pairs of right ventricular biopsy specimens taken before and after ischemia usually demonstrated deterioration of myocardium despite cardioplegia, and poor scores were predictive of hospital death. Use of a logistic analysis suggested that about half the hospital deaths were attributable to inadequate myocardial preservation despite cardioplegia.
3-dimensional crystalline arrays (Type I) of the ion transporting (Na+, K+)-ATPase enzyme from pig kidney develop in detergent-solubilized crude membrane-fragments or purified (Na+, K+)-ATPase preparations upon exposure to 0.1 M KCl and 0.1 M NaCl at pH 7.4 for several days at 2 degrees C in a crystallization medium that preserves the ATPase activity. Crystallization was obtained with non-ionic detergents; C12E8, C12E9, C12E10, and BRIJ 36 at a detergent: protein.ratio ranging from 1.8:1 to 4.4:1 in purified (Na+, K+)-ATPase preparations. High concentration of glycerol (40% v/v), Mg2+ ions and low temperature proved to be essential for crystallization and for protection of ATPase activity. Cross-linking of (Na+, K+)-ATPase crystals with glutaraldehyde protects the crystalline structure under conditions which otherwise disrupt the preformed crystals. The new crystals show close resemblance to the 3-dimensional crystals of the Ca(2+)-ATPase featuring the same structure of stacked lamellae. High-resolution electron microscopy of frozen-hydrated (Na+, K+)-ATPase samples is in progress to give unit cell dimensions and molecular packing of the new crystals.
This study evaluates cross-immunity in rhesus monkeys (Macaca mulatta) previously infected with one species of Leishmania and have had self-cured disease or were cured by antimony-based therapy upon development of full-blown disease. We found that a self-healing cutaneous leishmaniasis (CL) following experimental infection with Leishmania (Leishmania) major induces significant protection for L. (L.) amazonensis and L. (Viannia) guyanensis, and was dependent on time of re-challenge by L (L.) amazonensis after animals had recovered from primary lesions, but lacked protection against L. (V.) braziliensis. In contrast, monkeys that recovered from L. (V.) braziliensis CL or L. (L.) chagasi visceral leishmaniasis following chemotherapeutic intervention were protected by challenge with L. (V.) braziliensis and L (L.) amazonensis. These findings indicate the relative variability in protection after self-cure or drug-cured experimental leishmaniasis to challenge by heterologous leishmanial parasites. Further studying the immune response may provide information regarding relevant factors influencing cross-protective immunity.
In this paper clinical and experimental studies are reviewed for evidence that monoclonal antibodies (MoAbs), directed against common epitopes in the core glycolipid region of lipopolysaccharide (LPS) of gram-negative bacteria, protect against the lethal effect of bacteremia of serologically unrelated gram-negative bacteria. Only those experimental studies that included control MoAbs and excluded the possibility of survival due to endotoxin tolerance, provided evidence for the protective efficacy of cross-reactive MoAbs. Two recently performed clinical trials evaluating the protective value of the MoAbs HA-1A and E5 showed beneficial effects (enhanced survival) by each MoAb in different subgroups of patients with proven gram-negative bacterial infections. It is concluded that immunotherapy by MoAbs is a promising new tool in the treatment of gram-negative bacterial septic shock. However, the pathophysiological mechanism of protection remains to be elucidated and the group of patients which may benefit most remains to be defined more clearly. Therefore, further experimental and clinical studies are warranted.
Antigen presenting cells (APCs) activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.
The FimA protein of Streptococcus parasanguis is a virulence factor in the rat model of endocarditis, and immunization with FimA protects rats against homologous bacterial challenge. Because FimA-like proteins are widespread among the oral streptococci, the leading cause of native valve endocarditis, we evaluated the ability of this vaccinogen to protect rats when challenged by other streptococcal species. Here we report that FimA vaccination produced antibodies that cross-reacted with and protected against challenge by the oral streptococci S. mitis, S. mutans, and S. salivarius. FimA thus has promise as a vaccinogen to control infective endocarditis caused by oral streptococci.
Five strains of infectious bronchitis virus isolated from commercial chickens from the state of Pennsylvania, USA during the years 1998 and 1999 were studied. The strains were selected for cross-challenge in specific pathogen free chickens and virus neutralization in chick embryos on the basis of partial S1 sequence amino acid identity values. The partial sequences analysed spanned the hypervariable amino terminus region of S1 from amino acid residues 48 to 219, based on the Beaudette strain. Using their S1 identity values, the strains represented a continuum of genetic, and thus antigenic, relationships. When compared with strain PA/5083/99, strain PA/Wolgemuth/98 had high sequence identity (96%) followed by PA/171/99 (85%), PA/5344/98 (70%) and PA/1220/98 (34%). The method of Archetti and Horsfall was used for calculating antigenic relatedness values of virus neutralization tests. The same formula was also applied to the percentage protection values of cross-challenge tests to derive protective relatedness values among the strains. The antigenic relatedness values, protective relatedness values, and the partial S1 sequence identity values were then analysed. The findings indicated partial S1 sequence identity values were more strongly correlated with protective relatedness values and than antigenic relatedness values.
To better characterize the translational regulation of lipoprotein lipase (LPL) by epinephrine, cytoplasmic extracts were prepared from 3T3-L1 adipocytes, 3T3-F442A adipocytes, and other nonadipocyte cell lines (C2 cells, 3T3 fibroblasts, and Chinese hamster ovary cells). After treatment with epinephrine, cell extracts from the adipocytes inhibited LPL translation in an in vitro translation assay, whereas extracts from the C2 cells and 3T3 fibroblasts did not affect LPL translation. To identify the region on the LPL mRNA that controlled translation, in vitro translation was carried out using constructs containing different LPL sequences. Specific deletion of the first 50 (1601-1650) nucleotides of the 3' untranslated region (UTR) resulted in a loss of translation inhibition. The addition of LPL 3' UTR to a heterologous reporter gene construct resulted in an inhibition of translation. Inhibition of the reporter LPL 3' UTR translation was demonstrated by the addition of epinephrine-treated cell extracts to an in vitro translation assay, as well as by transfection of this construct into 3T3-F442A cells, followed by treatment of the cells with epinephrine. Competition for a trans-acting binding protein was demonstrated by the addition of sense mRNA strands corresponding to the proximal 135 nucleotides of the 3' UTR of LPL. To identify a RNA-binding protein, adipocyte extracts were incubated with 32P-labeled RNA sequences followed by RNase treatment. The epinephrine-treated cell extract protected a fragment of RNA when the RNA included sequences on the proximal 3' UTR of LPL. Cross-linking of this protected fragment and analysis by SDS-polyacrylamide gel electrophoresis revealed a protein that migrated at about 30 kDa. Thus, the addition of epinephrine to 3T3 adipocytes results in an inhibition of translation through the production of a RNA-binding protein that binds to a region on the proximal 3' UTR of the LPL mRNA.
The exotoxins produced by Staphylococcus aureus, staphylococcal enterotoxins (SE) A-E and toxic shock syndrome toxin (TSST)-1, which are associated with serious diseases, including food poisoning and toxic shock syndrome, are termed superantigens (SAgs). To examine whether common antigenic epitopes were present and whether vaccination with 1 bacterial SAg could protect against challenge with a different SE or TSST-1, mice were vaccinated with SEA, SEB, SEC1, or TSST-1 individually or in combination. Mice injected with a single toxin developed high antibody titers against other SAgs. Marked improvement in survival was observed when immunized mice were challenged with a heterologous toxin. Mice vaccinated with a mixture of toxins were fully protected against 1 or multiple toxin challenges, indicating no interference effects of multivalent vaccinations. More importantly, higher titers were found against each SAg with the multivalent vaccination than with injection with a single SAg. Thus, immunizations with 1 SAg can induce cross-protective antibodies to heterologous SAgs, and multicomponent vaccination can enhance antibody responses against each bacterial SAg.
OBJECTIVE: To establish the role of psychosocial risk and protective factors in cross-sectional variation in adolescent problem drinking, and in the transition into problem drinking over time. METHOD: The data were from a four-wave (1989-1992) longitudinal study of 1,591 adolescents in a large, urban school district. School district officials selected schools for the study with an aim toward maximizing representation of minority students from inner-city areas. At Wave 1, all students in Grades 7, 8, and 9 were asked to participate. RESULTS: Both psychosocial risk factors (such as low expectations for success, peer models for substance use, and poor school performance) and psychosocial protective factors (such as intolerance of deviance, peer models for conventional behavior, and involvement in prosocial activities) account for significant cross-sectional variation in adolescents' involvement in problem drinking, as indicated by more frequent drunkenness and more numerous instances of alcohol-related problems. They also account for significant variation in the timing of transition into problem drinking during adolescence. Higher risk and lower protection are each associated with greater problem use of alcohol. Among adolescents who are not problem drinkers, higher risk and lower protection accelerate the likelihood of becoming a problem drinker in subsequent years. Protection also moderates the impact of risk in the cross-sectional account of involvement in problem drinking, but protective factors appear not to play a moderating role in the longitudinal account of the transition into problem drinking. Findings were similar for males and females and among white, black and Hispanic adolescents. CONCLUSIONS: Protective factors play an independent role in accounting for adolescent involvement in problem drinking and in the transition into problem drinking in adolescence. Intervention efforts to enhance protection, especially for adolescents who are exposed to risk, should supplement efforts to reduce risk.
URF13 is a mitochondrially encoded, integral membrane protein found only in maize carrying the cms-T cytoplasm. URF13 is associated with cytoplasmic male sterility, Texas type, and causes susceptibility to the fungal pathogens Bipolaris maydis race T and Phyllosticta maydis. URF13 is predicted to contain three transmembrane alpha-helices and is a receptor for the pathotoxins (T-toxins) produced by B. maydis race T and P. maydis. Binding of T-toxin to URF13 leads to membrane permeability. Cross-linking of URF13 oligomers with N,N'-dicyclohexylcarbodiimide (DCCD) protects Escherichia coli cells expressing URF13 and cms-T mitochondria from the permeability caused by T-toxin or methomyl. Using mutated forms of URF13 expressed in E. coli cells, we determined the molecular mechanism of DCCD protection. We separately changed Lys-37 in helix II to isoleucine (K37I-URF13) and Lys-32 in the helix I/helix II loop region to alanine (K32A-URF13). DCCD treatment of K37I-URF13-expressing cells did not protect the cells from permeability caused by T-toxin or methomyl. DCCD cross-linking was greatly reduced in K37I-URF13 and in D39V-URF13-expressing cells, but it was unaffected in K32A-URF13-expressing cells. Binding of methomyl or T-toxin decreases DCCD cross-linking of URF13 oligomers expressed in either E. coli or cms-T mitochondria. We conclude that Asp-39 in helix II is cross-linked by DCCD to Lys-37 in helix II of an adjacent URF13 molecule and that this cross-linking protects against toxin-mediated permeabilization. Our results also indicate that helices II form a central core in URF13 oligomers.